formaldehyde study on kidney dialysis

Formaldehyde Studies on Kidneys

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The following information was generated from the Hazardous Substances Databank (HSDB), a database of the National Library of Medicine's TOXNET system (http://toxnet.nlm.nih.gov) on August 18, 2000.

Query: Information added from CHEMID: formaldehyde ( fannoform, formalith, formol, fyde, lysoform, morbicid, oxomethane, oxymethylene, superlysoform ) Registry Numbers: 50-00-0 1 NAME: FORMALDEHYDE HSN: 164 RN: 50-00-0 HUMAN HEALTH EFFECTS: EVIDENCE FOR CARCINOGENICITY: CLASSIFICATION: B1; probable human carcinogen. BASIS FOR CLASSIFICATION: Based on limited evidence in humans, and sufficient evidence in animals. Human data include nine studies that show statistically significant associations between site-specific respiratory neoplasms and exposure to formaldehyde or formaldehyde-containing products. An increased incidence of nasal squamous cell carcinomas was observed in long-term inhalation studies in rats and in mice. The classification is supported by in vitro genotoxicity data and formaldehyde's structural relationships to other carcinogenic aldehydes such as acetaldehyde. HUMAN CARCINOGENICITY DATA: Limited. ANIMAL CARCINOGENICITY DATA: Sufficient. [U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS) on Formaldehyde (50-00-0) Available from: http://www.epa.gov/ngispgm3/iris on the Substance File List as of March 15, 2000]**QC REVIEWED** A2. A2= Suspected human carcinogen. [American Conference of Governmental Industrial Hygienists. Threshold Limit Values (TLVs) for Chemical Substances and Physical Agents and BiologicalExposure Indices (BEIs) for 1995-1996. Cincinnati, OH: ACGIH, 1995. 22]**QC REVIEWED** Evaluation: There is limited evidence in humans for the carcinogenicity of formaldehyde. There is sufficient evidence in experimental animals for the carcinogenicity of formaldehyde. Overall evaluation: Formaldehyde is probably carcinogenic to humans (Group 2A). [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. 62 336 (1995)]**QC REVIEWED** HUMAN TOXICITY EXCERPTS: IF SOLN IS INGESTED, MUCOUS MEMBRANES OF MOUTH, THROAT, & INTESTINAL TRACT ARE IRRITATED, & SEVERE PAIN, VOMITING, & DIARRHEA RESULT. AFTER ABSORPTION, FORMALDEHYDE DEPRESSES CNS & SYMPTOMS NOT UNLIKE THOSE OF ALC INTOXICATION ARE NOTED. THEY CONSIST OF VERTIGO, DEPRESSION, & COMA. RARELY CONVULSIONS ARE OBSERVED. [Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975. 993]**PEER REVIEWED** ALTERATION OF TISSUE PROTEINS BY FORMALDEHYDE CAUSES LOCAL TOXICITY & PROMOTES ALLERGIC REACTIONS. REPEATED CONTACT WITH SOLN ... MAY CAUSE ECZEMATOID DERMATITIS. DERMATITIS FROM CLOTHING TREATED WITH FORMALDEHYDE ... HAS OCCURRED. [Gilman, A. G., L. S. Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 6th ed. New York: Macmillan Publishing Co., Inc. 1980. 971]**PEER REVIEWED** AQ SOLN ... SPLASHED OR DROPPED ON HUMAN EYES HAVE CAUSED INJURIES RANGING FROM SEVERE PERMANENT CORNEAL OPACIFICATION & LOSS OF VISION TO MINOR TRANSIENT INJURY OR DISCOMFORT, DEPENDING UPON WHETHER SOLN WERE OF HIGH OR LOW CONCN. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986. 443]**PEER REVIEWED** INHALATION OF HIGH CONCN ... CAUSED SEVERE IRRITATION OF RESP TRACT, LEADING IN 2 INSTANCES TO DEATH. ... PULMONARY EDEMA, WITH RESIDUAL CARDIAC IMPAIRMENT IN 1 CASE, WAS REPORTEDLY CAUSED BY SINGLE ACUTE INHALATIONS ... . [American Conference of Governmental Industrial Hygienists. Documentation of the Threshold Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH:American Conference of Governmental Industrial Hygienists, 1986. 276]**PEER REVIEWED** IN SENSITIZED SUBJECTS SPECIFIC LATE ASTHMATIC REACTIONS MAY BE PROVOKED BY BRIEF EXPOSURES AT APPROX 3 PPM. [HENDRICK DJ ET AL; J OCCUP MED 24 (11): 893 (1982)]**PEER REVIEWED** Ingestion of formaldehyde can cause a reduction in body temperature. [Environment Canada; Tech Info for Problem Spills: Formaldehyde p.83 (1985)]**PEER REVIEWED** Symptoms related to ingestion of formaldehyde include: jaundice, acidosis, and hematuria. Symptoms related to inhalation include: rhinitis, anosmia, laryngospasm, tracheitis, and gastroenteritis. [ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988. 250]**PEER REVIEWED** In a survey of 57 embalmers who were exposed to atmospheric concn below 2 ppm, there was a high incidence of symptoms of irritant effects on the eyes (81%) nose and throat (75%). Other respiratory effects included cough (33%), chest tightness (23%), wheezing (12%), and shortness of breath (11%). On the basis of the results, 10% were acute bronchitics, and 30% were chronic bronchitics. No control group was used and cigarette smoking was not taken into account. [Plunkett ER, Barbela T; Am Ind Hyg Assoc J 38: 61 (1977)]**PEER REVIEWED** Eyes: concn 1-10 ppm may produce appreciable eye irritation on initial exposure; lacrimation occurs at about 4 ppm. [Health and Safety Executive Monograph: Formaldehyde p.8 (1981)]**PEER REVIEWED** CULTURED BRONCHIAL & FIBROBLASTIC CELLS FROM HUMANS WERE USED TO STUDY DNA DAMAGE & TOXICITY. FORMATION OF CROSSLINKS BETWEEN DNA & PROTEINS, CAUSED SINGLE-STRAND BREAKS IN DNA, & INHIBITED RESEALING OF SINGLE-STRAND BREAKS PRODUCED BY IONIZING RADIATION. [GRAFSTROM RC ET AL; SCIENCE 220 (4593): 216-8 (1983)]**PEER REVIEWED** Formaldehyde induced a 1.5-3 fold increase in sister chromatid exchanges in ... human lymphocytes in culture. [Obe G, Beek B; Drug and Alcohol Dependence 4: 91-4 (1979)]**PEER REVIEWED** Formaldehyde was mutagenic for diploid human lymphoblasts in culture ... /inducing an incr number of mutations at/ 130 uM or 4 ppm by weight. [Goldmacher VS et al; Toxicol Epidemiol Mech (Pap Meet) 173-91 (1983)]**PEER REVIEWED** OUTBREAK OF HEMOLYTIC ANEMIA, ATTRIBUTED TO ACCIDENTAL EXPOSURE ... OCCURRED AMONG PATIENTS ON HEMODIALYSIS. 41 YR OLD WOMAN DIED 28 HR AFTER INGESTING 120 ML OF ... SOLN (37% WT/VOL FORMALDEHYDE, 12.5% VOL/VOL METHANOL, CONTAINING NO FORMIC ACID). [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. V29 369 (1982)]**PEER REVIEWED** EFFECTS IN WOMEN ATTRIBUTED TO EXPOSURE ... INCL MENSTRUAL DISORDERS & SECONDARY STERILITY. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. V29 370 (1982)]**PEER REVIEWED** SYMPTOMATOLOGY: A. Inhalation: 1. Irritation of mucous membranes, especially of eyes, nose and upper respiratory tract. 2. With higher concn, cough, dysphagia, bronchitis, pneumonia, edema or spasm of the larynx. Pulmonary edema is uncommon. B. Ingestion. 1. Immediate intense pain in mouth, pharynx and stomach. 2. Nausea, vomiting, hematemesis, abdominal pain and occasionally diarrhea (which may be bloody). 3. Pale, clammy skin and other signs of shock. 4. Difficult micturition, hematuria, anuria. 5. Vertigo, convulsions, stupor, and coma. 6. Death due to respiratory failure. C. Skin contact: 1. Irritation and hardening of skin. Strong solutions produce coagulation necrosis. 2. Dermatitis and hypersensitivity from prolonged or repeated exposure. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984.,p. III-197]**PEER REVIEWED** INVESTIGATIONS OF CILIOSTATIC EFFECT OF ALDEHYDES ARE OF SPECIAL INTEREST SINCE MANY HAVE IRRITATING EFFECT ON TRACHEAL MUCOSA. COMPARISON OF CILIOSTATIC EFFECT SHOWED FORMALDEHYDE TO BE MOST TOXIC FOLLOWED BY ACETALDEHYDE & ACROLEIN. CROTONALDEHYDE & METHACROLEIN SHOWED WEAKEST EFFECT. TECHNIQUE USED FOR OBSERVING TRACHEAL CILIARY ACTIVITY WAS THE IN VITRO TECHNIQUE. [DALHAMN T, ROSENGREN A; ARCH OTOLARYNGOL 93 (5): 496-500 (1971)]**PEER REVIEWED** One hundred nine workers and 254 control subjects were studied to evaluate the effects of formaldehyde on the mucous membranes and lungs. A modified, respiratory symptom questionnaire and spirometry were administered to all study participants before and after their work shift, and formaldehyde levels were determined for each test subject. Over the course of the monitored work shift, test subjects demonstrated a dose-dependent excess of irritant symptoms and a statistically significant decline in certain lung function parameters. Baseline spirometry values were not significantly different between test and control groups, and formaldehyde-exposed workers did not report an excess of respiratory symptoms. Formaldehyde is a dose-dependent irritant of the eyes and mucous membranes at low-level exposures. It can exert a small, across-shift effect on airways but after a mean exposure of ten years does not appear to cause permanent respiratory impairment. [Horvath EP et al; J Am Med Assoc 259 (5): 701-7 (1988)]**PEER REVIEWED** The effect of formaldehyde exposure on medical students conducting dissections in the gross anatomy laboratory course /was evaluated using/ self-administered questionnaires designed to assess the frequency of occurrence of various symptoms indicating the acute effects of formaldehyde exposure. The questionnaires were given to a cohort of first-year medical students on completion of the gross anatomy laboratory course. Air sampling of formaldehyde levels in the anatomy laboratories was carried out on one day during the time in which these students were conducting dissections. ... Although the results of the air sampling showed formaldehyde levels to be well below current occupational standards, significant numbers of students reported experiencing symtoms associated with formaldehyde exposure. Estimates of the relative risk of experiencing formaldehyde-related symptoms in the anatomy laboratories compared to the control laboratories ranged from 2.0 to 19.0, depending on the particular symptom. In addition, it was found that female students were three times more likely to report formaldehyde-related symptoms than male students. [Fleischer JM; NY J Med 87 (7): 385-8 (1987)]**PEER REVIEWED** A population based case control study was undertaken in 13 counties of western Washington to determine if occupational formaldehyde exposure was related to cancer of the oropharynx and hypopharynx (OHPC, N= 205), nasopharynx (NPC, N= 27) or sinus and nasal cavity (SNC, N= 53). Controls were selected by random digit dialing (N= 552). A telephone interview inquired about lifetime occupational history as well as a number of potential confounding factors, including smoking and drinking. Approximately half (N= 143) of the case interviews were with next of kin. ... Logistic regression was used to estimate exposure odds ratios STET while taking into account multiple risk factors for each site. No significant associations were found between occupational formaldehyde exposure and any of the cancer sites under study. However, relative risk estimates associated with the highest exposure score categories were evaluated for oropharynx and hypopharynx (OR= 1.3, 95% Confidence Interval= 0.6-3.1) and nasopharynx (OR= 2.1, 95% Cl= 0.4-10.0). When an induction period was accounted for only oropharynx and hypopharynx and nasopharynx increased to 1.7 and 3.1, respectively. Several limitations in the study tend to conservatively bias the results. ... [Vaughn TL et al; Int J Cancer 38 (5): 677-84 (1986)]**PEER REVIEWED** Because of the paucity of scientific data concerning the inhalation toxicity of formaldehyde in humans, determinations of the symptoms and alterations in pulmonary function resulting from inhalation for 1 hr of 3 ppm formaldehyde were studied. The protocol consisted of randomized exposure of each subject to clean air or 3.0 ppm formaldehyde on 2 separate days. Twenty-two healthy normal subjects engaged in intermittent heavy exercise (VE= 65 /min) and 16 asthmatic subjects performed intermittent moderate exercise (VE= 37 /min). Symptoms and pulmonary functions were assessed during the time course of exposure; nonspecific airway reactivity was assessed after exposure. Both groups exhibited similar, significant (p < 0.01) increases in perceived odor, nose/throat irritation, and eye irritation throughout the exposure. The non-asthmatic group had the following slight but statistically significant (p < 0.02) lower pulmonary functions after 55 min of exposure to formaldehyde as compared to clean air: 3.8% in FEV1, 2.6% in FVC, and 2.8% in FEV3. The asthmatic group showed no statistically significant decrements in pulmonary function. [Green DJ et al; Am Rev Respir Dis 135 (6): 1261-6 (1987)]**PEER REVIEWED** A retrospective mortality analysis was conducted in a cohort of 9,365 individuals employed as of 1940 in two chrome leather tanneries in the United States and followed to the end of 1982. Vital status as of the closing date was determined for over 95% of the cohort. Potential hazardous workplace exposures varied with department and included ... formaldehyde. ... Mortality from all causes combined was lower than expected for each tannery. ... Deaths from cancer of each site, including the lung, were also lower than expected compared to those of either the population of the United States or of local state rates. A significant excess of deaths was observed, however, due to accidental causes in one tannery and cirrhosis of the liver, suicide, and alcoholism in the other. These excesses did not appear to be casually associated with occupational exposures. [Stern FB et al; Scand J Work Environ Health 13 (2): 108-17 (1987)]**PEER REVIEWED** Infectivity of human T-cell lymphotropic virus, Type III (HTLV-III) was ... efficiently inactivated by formalin ... . [Quinnan GV et al; Transfusion 26 (5): 481-3 (1986)]**PEER REVIEWED** Eight symptomatic individuals chronically exposed to indoor formaldehyde at low concentrations (0.07-0.55 ppm) were compared to 8 nonexposed subjects with respect to: (1) presence of IgG and IgE antibodies to formaldehyde conjugated to human serum albumin (F-HSA); (2) the percentage of venous blood T- and B-cells by E- and EAC-rosetting; and (3) the ability of T- and B-cells to undergo mitogen (phytohemagglutin and pokeweed) stimulated blastogenesis as measured by the incorporation of tritiated thymidine. Anti-F-HSA IgG, but not IgE, antibodies were detected in the sera of the 8 exposed subjects; none were found in 7 of the controls. T-lymphocytes were decreased in the exposed (48%) compared to the control (65.9%) subjects (p < 0.01). B-cells were 12.6% (exposed group) and 14.75% (controls) (p < 0.05). The incorporation of labeled thymidine by T-cells (phytohemagglutin) was decreased: 17,882 cpm (exposed group) and 28,576 cpm (p < 0.01). T- and B-cell blastogenesis (pokeweed) was 9,698 cpm (exposed group) and 11,279 (controls) (p < 0.1). [Thrasher JD et al; Arch Environ Health 42 (6): 347-50 (1987)]**PEER REVIEWED** Some alcoholic solutions /of formaldehyde/ are used industrially & the physical properties & hazards may be greatly influenced by the solvent. [Sax, N.I. Dangerous Properties of Industrial Materials. 6th ed. New York, NY: Van Nostrand Reinhold, 1984. 1451]**PEER REVIEWED** Both death and survival from 4-oz formalin ingestions have been reported in adults. The probable mean lethal adult dose is 1 to 2 oz. Death may occur within 3 hours; survival past 48 hours usually means recovery. [Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 1002]**PEER REVIEWED** An environmental survey of two wood products (plywood, particle-board) companies revealed mean concentrations in the plywood forming areas of 0.8 ppm and, in two particle-board forming areas, of 1.1 to 1.4 ppm /formaldehyde/. Ophthalmologic evaluations were conducted and eye irritation self-reports were collected from 84 subject workers, including unexposed controls, from various areas in the plants. Results from both were unremarkable, as were tests mapping their visual fields. However, there were subjective reports of at least occasional eye irritation in 67% of the exposed subjects, with more such reports coming from workers in areas of the plant with the higher concentrations. An explosion at the factory closed a major product line and resulted in laying off many of the volunteer subjects prior to performance testing; the remaining 49 workers were tested before and after their workshift (and 13 of them were tested on 2 days) in order to assess acute effects of formaldehyde on visual acuity, depth perception, peripheral vision, accommodation, eye movement and fixation, divided attention, and color vision. Subjective reports of eye irritation on the day of testing did not correlate, or correlated negatively, with formaldehyde concentrations on the test day, which averaged 0.4 ppm. Average visual test scores were better at the end of the day than at the beginning, and there was a trend for those with higher formaldehyde levels to demonstrate greater improvement. Some of the changes reached traditional levels of statistical significance. The results from this investigation, while relevant to the neurotoxicity of formaldehyde, suffer from the small sample size and the possibility that the comparison subjects had also experienced formaldehyde exposure. With these caveats, this study suggests that mean formaldehyde exposures at 0.4 ppm produce no deleterious acute effects on visual performance, but chronic exposures between 0.8 and 1.4 ppm may produce an increased incidence of self reported symptoms of eye irritation in persons who do not have clinical ophthalmologic defects. [O'Donoghue, J.L. (ed.). Neurotoxicity of Industrial and Commercial Chemicals. Volume I. Boca Raton, FL: CRC Press, Inc., 1985. 59]**PEER REVIEWED** Symptoms: Local: Conjunctivitis, corneal burns; brownish discoloration of skin; dermatitis, urticaria (hives), pustulovesicular eruption. Inhalation: rhinitis and anosmia (loss of sense of smell); pharyngitis, laryngospasm; tracheitis and bronchitis; pulmonary edema, cough, constriction in chest; dypsnea (difficult breathing), headache, weakness, palpitation (rapid heart beat), gastro enteritis (inflammation of the stomach and intestines). Ingestion: Burning in mouth and esophagus; nausea and vomiting; abdominal pain, diarrhea, vertigo (dizziness), unconsciousness, jaundice, albuminuria, hematuria, anuria, acidosis, convulsions. [ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988. 249]**PEER REVIEWED** Aldehydes increase airflow at concentrations below those that decrease respiratory frequency. /Aldehydes/ [Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 1618]**PEER REVIEWED** Levels of formaldehyde exposure were measured in the dissecting facilities of the biology department of Montclair State College, Montclair, New Jersey during the 1982 through 1983 academic year. An air sampling pump was fitted with two impingers and used to collect air samples at a rate of 1 l/min for 1 hr at each site. A chromotropic acid/sulfuric acid solution was used to form a purple monocationic chromogen with formaldehyde, and absorbance was measured spectrophotometrically at 580 nanometers. Sampling sites and concentrations in ppm at each included a teaching lab (range from 7.0 to 16.5 ppm), rear stock room (range from 1.97 to 2.62 ppm), and a public hallway (less than 1.0 ppm). Both the 7 and the 16.5 ppm levels were above the standard established by OSHA and the standard of 2 ppm established by the American Conference of Governmental Industrial Hygienists. The 2.62 ppm reading was above the standard of 1 ppm for 30 minute exposures as recommended by NIOSH. [Korky JK et al; Bull Environ Contam Toxicol 38 (5): 907-10 (1987)]**PEER REVIEWED** Data on concentration of formaldehyde and 15 organic solvents in Finnish furniture factories from 1975 to 1984 were presented. Workers often complained of severe eye, nose, and upper respiratory tract irritation. Formaldehyde was collected in a 1% sodium bisulfite solution and analyzed by the chromatropic method. The solvents were adsorbed in a charcoal tube, desorbed with carbon-disulfide or dimethylformamide, and analyzed by gas chromatography. All highly exposed workers were monitored. The widest range of formaldehyde concentration was recorded in the operation of the curtain painting furniture receiving operation, which was between 0.2 and 5.4 ppm. The mean concentrations of most organic solvents studied ranged from 4 to 66 ppm. Formaldehyde levels were high and the 1 ppm exposure limit, defined as the 15 minute time weighted average by the Finnish Board of Labor Protection, was exceeded about 40% of the time. [Priha E et al; Ann Occup Hyg 30 (3): 289-94 (1986)]**PEER REVIEWED** A study of 759 histologically verified cancers of the nasal cavity (287 cases), paranasal sinuses (179 cases), and nasopharynx (293 cases) and 2465 cancer controls diagnosed in Denmark between 1970 and 1982 was conducted to investigate the importance of occupational exposure to formaldehyde. Information on job history for cases and controls was derived from a national data linkage system and exposure to formaldehyde and wood dust was assessed by industrial hygienists unaware of the case control status of the patients. The exposure rates for formaldehyde among male and female controls were 4.2% and 0.1% respectively. After proper adjustment for contemporary wood dust exposure, relative risk of 2.3 (95% CI= 0.9-5.8) for squamous cell carcinoma and 2.2 (95% CI= 7-7.2) for adenocarcinoma of the nasal cavity and paranasal sinuses were detected among men who have been exposed to formaldehyde in their job compared with those never exposed. [Olsen JH, Asnaes S; Br J Ind Med 43 (11): 769-74 (1986)]**PEER REVIEWED** The National Cancer Institute study on the relationship between exposure to formaldehyde and mortality from nasophryngeal cancer was evaluated. The study had indicated little evidence of a link between formaldehyde at concentrations normally encountered in the workplace and risk of nasopharyngeal cancer. Although the overall standardized mortality ration was significantly elevated in subjects exposed to formaldehyde, the overall risk did not increase with increasing intensity of exposure. A reanalysis, however, suggested that simultaneous exposure to poarticulates and formaldehyde could be a risk factor. A further review of the National Cancer Institute findings showed that the significant excess mortality was based on deaths occurring in a single factory (factory-A) and occurred primarily in short term employess. When the data were analyzed in terms of cumulative exposures that were known to include both formaldehyde and particulates, only the highest exposure group had a significantly increased excess nasopharyngeal cancer mortality. This excess was clearly located in factory-A. A followup study of factory-A that added 5 more years of followup was initiated. It showed no additional deaths from nasopharyngeal cancer even among workers with the highest formaldehyde and particulate exposures. The four deaths from nasopharyngeal cancer in this factory occurred in workers employed in the same department and hired between 1949 and 1955. Although these workers were exposed to formaldehyde and particulates, they were not among the most highly exposed. [Collins JJ et al; J NCI 80 (5): 376-7 (1988)]**PEER REVIEWED** This study evaluates the histological changes, especially the presence of possible precancerous lesions, in the nasal mucosa of workers exposed to formaldehyde. Nasal biopsies of 37 workers occupationally exposed to formaldehyde for more than five years and 37 age matched referents showed a higher degree of metaplastic alterations in the former group. In addition, three cases of epithelial dysplasia were observed among the exposed. These results indicate that formaldehyde may be potentially carcinogenic in man. Combination of this finding with the inconclusive epidemiological studies suggests that formaldehyde is a weak carcinogen and that occupational exposure to formaldehyde alone is insufficient to induce nasal cancer. [Boysen M et al; Br J Ind Med 47 (2): 116-21 (1990)]**PEER REVIEWED** Clinical and animal studies suggest that formaldehyde adsorbed on respirable particles may elicit a greater pulmonary physiologic and inflammatory effect than gaseous formaldehyde alone. This study was to determine if respirable carbon particles have a synergistic effect on the acute symptomatic and pulmonary physiologic response to formaldehyde inhalation. Normal, nonsmoking, methacholine-nonreactive subjects were exposed to 2 hr each of clean air, 3 ppm formaldehyde, 0.5 mg/cu m respirable activated carbon aerosol, and the combination of 3 ppm formaldehyde plus activated carbon aerosol. The subjects engaged in intermittent heavy exercise (VE= 57 1/min) for 15 min each half hour. Formaldehyde exposure was associated with significant increases in reported eye irritation, nasal irritation, throat irritation, headache, chest discomfort, and odor. Synergistic increases in cough, but not in other irritant respiratory tract symptoms, were observed with inhalation of formaldehyde and carbon. Small (less than 5%) synergistic decreases in FVC and FEV3 were also seen. No formaldehyde effect was observed on FEV1; however, we did observe small (less than 10%) significant decreases in FEF25-75%, which may be indicative of increased airway tone. Overall, results demonstrated synergism, but the effect is small and its clinical significance is uncertain. [Green DJ et al; J Toxicol Environ Health 28 (3): 261-75 (1989)]**PEER REVIEWED** To study the cytotoxic effect of formaldehyde on the human nasal mucosa 75 men with occupational exposure to formaldehyde or to formaldehyde and wood dust, were examined, looking particularly at early signs of irritative effects and histopathological at early signs of irritative effects and histopathological changes in the nasal mucosa. A nasal biopsy specimen was graded from 0-8 according to the morphological changes. A high frequency of nasal symptoms, mostly a running nose and crusting, was related to exposure to formaldehyde. Only three men had a normal mucosa; the remainder has loss of cilia and goblet cell hyperplasia (11%) and squamous metapolasia (78%); in six cases (8%) there was a mild dysplasia. The histological grading showed a significantly higher score when compared with unexposed controls (2.9 v 1.8). There was no dose response relation, no malignancies, and no difference in the histological score between those exposed to formaldehyde or to formaldehyde and wood dust. [Edling C et al; Br J Ind Med 45 (11): 761-5 (1988)]**PEER REVIEWED** A study of respiratory symptoms and pathophysiological effects associated with occupational exposure to formaldehyde and wood dust was conducted. The cohort consisted of 70 Swedish workers exposed to formaldehyde during the production of formaldehyde and formaldehyde based products (formaldehyde group) and 100 furniture workers exposed to formaldehyde and wood dust (formaldehyde/wood dust group). The comparisons consisted of 36 local government clerks. The formaldehyde group was exposed to 0.05 to 0.5 mg/cu m formaldehyde and the furniture workers to 0.2 to 0.3 mg/cu m formaldehyde and 1 to 2 mg/cu m wood dust. Annual formaldehyde exposures of the comparisons averaged 0.09 mg/cu m. Sixty four percent of the formaldehyde group, 53% of the formaldehyde/wood dust group, and 25% of the comparisons reported nasal discomfort. Symptoms from the lower airways were reported by 44% of the formaldehyde group, 39% of the formaldehyde/wood dust group, and 14 % of the comparisons. Symptoms of nasal obstruction and watery discharges were more frequent in the exposed subjects than in the comparisons. More pronounced nasal swelling was found in the cohort than in the comparisons. 20% of the formaldehyde and 15% of the formaldehyde/wood dust group had impaired mucociliary clearance versus only 3% of the comparisons. Both exposed groups had a reduced sense of smell. Forced vital capacity was significantly decreased in the exposed groups. [Holmstorm M, Wilhelmsson B; Scandinavian J Work Environ Health 14 (5): 306-11 (1988)]**PEER REVIEWED** A study was conducted to determine if pathologists with exposure to formaldehyde demonstrate an excess risk of cancer, particularly cancers of the nasopharyngeal and pharyngeal areas. A population of 6411 physicians with occupational formaldehyde exposure participated in the study. The occurrence of these types of cancers was 4.7 times higher in these persons than in a comparable sized group of psychiatrists, but even so it is difficult to determine the importance of this increased risk as being directly tied to formaldehyde exposure. Pathologists and other members of the study group were exposed to other chemicals and infectious agents as well as formaldehyde. There was an apparent excess of mortality from pancreatic cancer and brain cancers as well as leukemia. [Matanoski GM; Risks of Pathologists Exposed to Formaldehyde School of Hygiene and Public Health, Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, Grant No. RO1-OH-01511 (1989)]**PEER REVIEWED** The relation of chronic respiratory symptoms and pulmonary function to formaldehyde in homes was studied in a sample of 298 children (6-15 years of age) and 613 adults. Formaldehyde measurements were made with passive samplers during two 1 wk periods. Significantly greater prevalence rates of asthma and chronic bronchitis were found in children from houses with formaldehyde levels 60-120 ppb than in those less exposed, especially in children also exposed to environmental tobacco smoke. In children, levels of peak expiratory flow rates decreased linearly with formaldehyde exposur, with the estimated decrease due to 60 ppb of formaldehyde equivalent to 22% of peak expiratory flow rates level in nonexposed children. The effects in asthmatic children exposed to formaldehyde below 50 ppb were greater than in healthy ones. The effects in adults were less evident: decrements in peak expiratory flow rates due to formaldehyde over 40 ppb were seen only in the morning, and mainly in smokers. [Krzyzanowski M et al; Environ Res 52 (2): 117-25 (1990)]**PEER REVIEWED** The long term effects of formaldehyde on the respiratory tract have been investigated in a group of 164 workers exposed daily to the chemical during the production of urea formaldehyde resin, together with 129 workers not exposed to free formaldehyde. Exposure was classified as high (corresponding to an eight hour time weighted exposure of more than 2.0 ppm), medium (0.6 to 2.0 ppm), or low (0.1 to 0.5 ppm). 25% of workers had high exposure at some time and 17% moderate exposure. Both exposed and unexposed groups had an annual assessment that included lung function. The proportion with self reported respiratory symptoms was similar in the two groups, 12% and 16% reporting breathlessness on hurrying and 26% and 20% wheezing. The initial forced expiratory volume in one second was within 0.5 l (approximately on standard deviation) of the predicted value (by age and height) in 65% of the exposed and 59% of unexposed workers and more than 0.5 l below the predicted value in 9% of exposed and 11% unexposed workers. The mean decline in forced expiratory volume in one second was 42 ml a year (standard deviation 45) in the exposed and 41 ml a year in the unexposed group (standard deviation 40 ml a year). The rate of decline showed the expected association with smoking in the unexposed group, but in the exposed group the mean rate of decline in the never smokers was similar to that in current smokers. There were, however, relatively few never smokers and considerable variation in the rates of decline. In the exposed group no association was found between the rate of decline and indices of exposure to formaldehyde. Thus there is no evidence from this study of an excess of respiratory symptoms or decline in lung function in the workers exposed to formaldehyde. The similar rate of decline of forced expiratory volume in one second however in never smokers and smokers of the exposed group is consistent with finding of other studies for workers exposed to formaldehyde. [Nunn AJ et al; Br J Ind Med 47 (11): 747-52 (1990)]**PEER REVIEWED** A prospective evaluation of pulmonary function and respiratory symptoms was conducted among 103 medical students exposed to formaldehyde over a 7 month period to determine the incidence of bronchoconstriction and respiratory symptoms in response to exposure. Time-weighted average formaldehyde exposures were generally less than 1 ppm and peak exposures were less than 5 ppm. Acute symptoms of eye and upper respiratory irritation were significantly associated with exposure. There was no pattern of bronchoconstriction in response to exposure after either 2 weeks or 7 months. Twelve subjects had a history of asthma; they were likely to have symptoms of respiratory irritation or changes in pulmonary function than those without such a history. These findings are consistent with previous case reports that indicate exposure to formaldehyde vapor at levels that are commonly encountered in occupational and residential seetings do not commonly cause significant bronchonconstriction, even among subjects with preexisting asthma. [Uba G et al; Am J Ind Med 15 (1): 91-101 (1989)]**PEER REVIEWED** A case of anaphylactoid reaction to a patch test with formaldehyde was described. The 40 year old woman developed bronchospasm and laryngospasm following the inhalation of formaldehyde vapor. A year later she accidentally entered a hospital room relatively soon after it had been disinfected, and was hospitalized with dyspnea, cyanosis, bronchospasm, and laryngospasm. Days later she did react to a patch test with a 1% solution of formaldehyde in water. Pulmonary function tests 20 min after the patch test revealed a 50% reduction in FEV1 and a 63% reduction in MEF 25. [Orlandini A et al; Contact Dermatitis 19 (5): 383-4 (1988)]**PEER REVIEWED** Four groups of patients with long-term inhalation exposure to formaldehyde were compared with controls who had short-term periodic exposure to formaldehyde. The following were determined for all groups: total white cell, lymphocyte, and T cell counts; T helper/suppressor ratios; total Ta1+, IL2+, and B cell counts; antibodies to formaldehyde-human serum albumin conjugate and autoantibodies. When compared with the controls, the patients had significantly higer antibody titers to formaldehyde-human serum albumin. In addition, significant increases in Ta1+, IL2+, and B cells and autoantibodies were observed. Immune activation, autoantibodies, and anti formaldehyde-human serum albumin antibodies are associated with long-term formaldehyde inhalation. [Thrasher JD et al; Arch Environ Health 45 (4): 217-23 (1990)]**PEER REVIEWED** The incidence of spontaneous abortions among hospital staff who used ethylene oxide, glutaral (glutaraldehyde) and formaldehyde for the chemical sterilization of instruments was studied using data from a questionnaire and a hospital discharge register. ... When the staff were concerned in sterilizing during their pregnancy the frequency was 16.7% compared with 5.6% for the nonexposed pregnancies. The incr frequency ... correlated with exposure to ethylene oxide but not with exposure to glutaral or formaldehyde. [Hemminki K et al; Brit Med J 285: 1461-63 (1982)]**PEER REVIEWED** Employees exposed to formaldehyde in the woodworking industry and nonexposed control subjects were examined by spirometry and the nitrogen washout technique. A dose-response relationship was found between exposure to formaldehyde and decrease in lung function. Industrial exposure to formaldehyde causes transient lung function impairment over a work shift, with a cumulative effect over the years. The impairment, however, can be reversed with 4 wk of no exposure. [Alexandersson R, Hedenstierna G; Arch Environ Health 44 (1): 5-11 (1989)]**PEER REVIEWED** The mortality of 1,332 male workers employed at least 30 days in 1959-1980 in a resins-manufacturing plant was examined. Ambient measurements taken in the plant between 1974 and 1979 documented a potential for exposure to levels of formaldehyde as high or greater than 3.0 mg/cu m. Vital status was ascertained for 98.6% of the cohort members, and their mortality was compared with expected deaths drawn from the national and local population rates. A statistically significant increase in lung cancer was observed, based on 18 deaths, which was not fully accounted for by possible confounding factors linked to personal habits or sociocultural characteristics. This elevated risk, however, could not be attributed specifically to exposure to formaldehyde. Mortality from digestive cancer (14 deaths observed) and hematologic neoplasms (5 deaths observed) was not substantially higher than expected. [Bertazzi PA et al; Scand J Work Environ Health 12 (5): 461-8 (1986)]**PEER REVIEWED** SKIN, EYE AND RESPIRATORY IRRITATIONS: Contact with the skin causes irritation, tanning effect, and allergic sensitization. Contact with eyes causes irritation, itching, & lacrimation. ... [Environment Canada; Tech Info for Problem Spills: Formaldehyde p.2 (1985)]**PEER REVIEWED** MEDICAL SURVEILLANCE: Consider the skin, eyes, & resp tract in any placement or periodic examination, esp if the patient has a history of allergies. [Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 1985. 464]**PEER REVIEWED** PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/ [Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory:Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979. 23]**PEER REVIEWED** POPULATIONS AT SPECIAL RISK: Mean formaldehyde levels are highest in hospital autopsy rooms compared with other commercial settings. /Hospital autopsy workers are possibly exposed/. [Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 1002]**PEER REVIEWED** Release of /formaldehyde/ vapors in mobile homes has been associated with headache and pulmonary and dermal irritation. /Occupants of mobile homes are possibly exposed/. [Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 1002]**PEER REVIEWED** PROBABLE ROUTES OF HUMAN EXPOSURE: Humans are exposed to formaldehyde from a variety of sources. The major source of atmospheric discharge is from combustion processes specifically from auto emissions and also from the photooxidation of hydrocarbons in auto emissions(1,2). Additional exposure to formaldehyde emissions comes from its use as an embalming fluid in anatomy labs, morgues, etc and its use as a fumigant and sterilant(1). Resin treated fabric, rugs, paper, etc and materials such as particle board and plywood which use resin adhesives and foam insulation release formaldehyde which may build up in homes and occupational atmospheres(1,2). Contact with industrial waste water, especially from lumber related operations where formaldehyde is used in adhesives, has resulted in the Pacific Northwest, Northeast, parts of Texas, and lumber areas of the south(1)(SRC). The estimated daily intake of formaldehyde among exposed Finnish workers is 3000 ug, whereas heavily exposed workers (particle-board and glue production, foundry work) is 10,000 ug(3). [(1) Kitchens JF et al; Investigation of Selected Potential Environmental Contaminants: Formaldehyde p. 22-98 USEPA 560/2-76-009 (1976) (2) National Research Council; Formaldehyde and Other Aldehydes p. 2-1 to 5-96 USEPA 600/6-82-002 (1982) (3) Hemminki K, Vainio H; Human Exposure to Potentially Carcinogenic Compounds. IARC Sci Publ 59: 37-45 (1984)]**PEER REVIEWED** Health hazards unique to particle board include the generation of urea-formaldehyde resin bound in wood aerosol and release of formaldehyde gas that can be inhaled by the worker. A particle board aerosol was generated by a sanding process and collected under laboratory conditions that determined the particle size distribution and formaldehyde content. Significant variations (p < 0.005) were observed for the particle board mass and gaseous formaldehyde collected between sample runs. No significant differences were observed for the aerosol size distribution determined and formaldehyde content in particle board aerosol per unit mass for sampling trials. [Stumpf JM et al; Am Indus Hyg Assoc J 47 (12): 725-30 (1986)]**PEER REVIEWED** ... /VAPORS/ GIVEN OFF DURING HOT MOLDING OF SYNTH RESINS (/IS A/ COMMON SOURCE OF EXPOSURE) ... A SURVEY OF 6 FUNERAL HOMES ... REVEALED MEAN CONCN, IN DIFFERENT ESTABLISHMENTS, BETWEEN 0.25 & 1.39 PPM. ... /EXPOSURES ARE ENCOUNTERED/ IN PHENOL-FORMALDEHYDE RESIN MOULDING PLANT ... /FROM WHICH/ CHRONIC AIRWAY OBSTRUCTION LOWERED FORCED EXPIRATORY VOL/FORCED VOL CAPACITY RATIO & EYE, NOSE & THROAT IRRITATION & LOWER RESP TRACT SYMPTOMS /HAVE BEEN OBSERVED/. [American Conference of Governmental Industrial Hygienists. Documentation of the Threshold Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH:American Conference of Governmental Industrial Hygienists, 1986. 276]**PEER REVIEWED** ... /EXPOSURES TO/ FORMALDEHYDE VAPOR EMISSIONS IN PERMANENT-PRESS FABRICS INDUSTRY (8 PLANTS) /HAVE BEEN REPORTED IN WHICH/ CONCN RANGING ... FROM 0.3 TO 2.7 PPM (IN SEWING AREA) WITH AVG OF 0.68 PPM /WERE DETECTED/. COMPLAINTS CONSISTED OF ANNOYING ODOR (ODOR THRESHOLD, BELOW 1.0 PPM), CONSTANT PRICKLING IRRITATION OF MUCOUS MEMBRANES & DISTURBED SLEEP. [American Conference of Governmental Industrial Hygienists. Documentation of the Threshold Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH:American Conference of Governmental Industrial Hygienists, 1986. 276]**PEER REVIEWED** FORTY-SEVEN SUBJECTS EXPOSED TO FORMALDEHYDE (MEAN AIR CONCN 0.45 MG/CU M) & 20 UNEXPOSED SUBJECTS, ALL EMPLOYED IN CARPENTRY SHOP WERE STUDIED. SYMPTOMS INVOLVING EYES & THROAT AS WELL AS CHEST OPPRESSION WERE SIGNIFICANTLY MORE COMMON IN EXPOSED THAN IN UNEXPOSED. [ALEXANDERSSON R ET AL; ARCH ENVIRON HEALTH 37 (5): 279-84 (1982)]**PEER REVIEWED** NIOSH (NOES 1981-1983) has statistically estimated that 206,935 workers are exposed to formaldehyde in the USA(5). In a 12-week study of exposure in a gross anatomy lab of a medical school, 44% of breathing room samples and 11% of ambient air samples were > 1.0 ppm the ceiling recommended by ACGIH; Half the breathing zone samples were between 0.6-1.0 ppm and the range was 0.3-2.63 ppm(1). A 1976 report estimates that 8000 US workers were potentially exposed to formaldehyde during its production(3). A more recent estimate of the number of exposed workers in industries producing and using formaldehyde and its derivatives range from 1.4-1.75 million(2). Concentrations of formaldehyde in occupational areas dating from the 1960's and early 1970's are: textile plant 0-2.7 ppm, 0.68 ppm avg; garment factory 0.9-2.7 ppm; clothing store 0.9-3.3 ppm; laminating plant 0.04-10 ppm; funeral homes 0.09-5.26 ppm, 0.25-1.39 ppm avg; resin manufacture and paper production 16-30 ppm; paper conditioning 0.9-1.6 ppm; wood processing 31.2 ppm max(2). Concns in occupational settings dating from the late 70's are: textile plants 0.1-0.5 ppm, 0.2 ppm avg; shoe factory 0.9-2.7 ppm, 1.9 ppm avg; particle board plant 0.1-4.9 ppm, 1.15 ppm avg; plywood plant 0.1-1.2 ppm, 0.35 ppm avg; wooden furniture manufacturing plant 0.1-5.4 ppm, 1.35 ppm avg; adhesive plants 0.8-3.5 ppm, 1.75 ppm avg; foundries 0.05-2.0 ppm, 0.6 ppm avg; construction sites 0.5-7.0 ppm, 2.8 ppm avg; hospitals and clinics 0.05-3.5 ppm, 0.7 ppm avg(2). More recent survey results for occupational environments include: fertilizer production 0.2-1.9 ppm; dyestuffs < 0.1-5.8 ppm; textile manufacture < 0.1-1.4 ppm; resins (foundry) < 0.1-5.5 ppm; bronze foundry 0.12-0.8 ppm; iron foundry < 0.02-18.3 ppm; treated paper 0.14-0.99 ppm; hospital autopsy room 2.2-7.9 ppm; plywood industry 1.0-2.5 ppm; urea-formaldehyde foam applicators < 0.08-2.4 ppm(4). [(1) Skisak, CM; Amer Ind Hyg Assoc J 44: 948-50 (1983) (2) IARC; Monograph. Some Industrial Chemicals and Dyestuffs 29: 345-89 (1982) (3) National Research Council; Formaldehyde and other Aldehydes p.2-1 to 5-96 USEPA 600/6-82-002 (1982) (4) Bernstein RS et al; Am Ind Hyg Assoc J; 45: 778-85 (1984) (5) NIOSH; National Occupational Exposure Survey (1985)]**PEER REVIEWED** AVERAGE DAILY INTAKE: AIR INTAKE (assume 2-20 ppb) 50-500 ug; in energy efficient houses (assume 212 ppb day, 114 ppb night) 4500 ug;. The estimated daily exposure of the Finnish population to formaldehyde from community air is 100 ug and from the home environment, 1000 ug(1); WATER INTAKE (assume 0 ppb) 0 ug; FOOD - insufficient data.; TOBACCO - 50 ug(1). [(1) Hemminki K, Vainio H; Human Exposure to Potentially Carcinogenic Compounds. IARC Sci Publ 59: 37-45 (1984)]**PEER REVIEWED** MINIMUM FATAL DOSE LEVEL: Approximate Minimum Lethal Dose (MLD) (150-lb man): 30 ml [Arena, J. M. Poisoning: Toxicology, Symptoms, Treatments. Fourth Edition. Springfield, Illinois: Charles C. Thomas, Publisher, 1979. 97]**PEER REVIEWED** EMERGENCY MEDICAL TREATMENT: EMERGENCY MEDICAL TREATMENT: EMT COPYRIGHT DISCLAIMER: Portions of the POISINDEX(R) database are provided here for general reference. THE COMPLETE POISINDEX(R) DATABASE, AVAILABLE FROM MICROMEDEX, SHOULD BE CONSULTED FOR ASSISTANCE IN THE DIAGNOSIS OR TREATMENT OF SPECIFIC CASES. Copyright 1974-1998 Micromedex, Inc. Denver, Colorado. All Rights Reserved. Any duplication, replication or redistribution of all or part of the POISINDEX(R) database is a violation of Micromedex' copyrights and is strictly prohibited.
The following Overview, *** FORMALDEHYDE ***, is relevant for this HSDB record chemical. LIFE SUPPORT: o This overview assumes that basic life support measures have been instituted. CLINICAL EFFECTS: SUMMARY OF EXPOSURE 0.2.1.1 ACUTE EXPOSURE o INGESTION may cause corrosive injury to the gastrointestinal mucosa, with nausea, vomiting, pain, bleeding, and perforation. Systemic effects include CNS depression, coma, and metabolic acidosis. o INHALATION - Respiratory tract irritation, wheezing, and laryngospasm may develop. Lower respiratory effects, including bronchitis and pneumonia, may develop with significant exposure. o DERMAL - Irritant dermatitis may develop; resins containing formaldehyde can cause epidermal necrosis. o OCULAR (vapor) - Irritation and lacrimation may develop with exposure to vapors. o OCULAR (liquid) - Solutions with high formaldehyde concentrations may produce severe corneal opacification and loss of vision. Solutions containing low formaldehyde concentrations may produce transient discomfort and irritation. VITAL SIGNS 0.2.3.1 ACUTE EXPOSURE o Shock may develop with severe exposures. Tachypnea may develop in patients with metabolic acidosis. Reduction in body temperature may be seen. HEENT 0.2.4.1 ACUTE EXPOSURE o IRRITATION of the eyes, nose, and throat may occur following exposure to formaldehyde OR fumes from urea-formaldehyde foam and adhesive resins. o Corneal opacification and loss of vision may occur following direct eye splash exposure to solutions containing high concentrations of formaldehyde. Transient discomfort and irritation may result from eye exposure to solutions containing low concentrations of formaldehyde. CARDIOVASCULAR 0.2.5.1 ACUTE EXPOSURE o Hypotension and cardiovascular collapse may occur. RESPIRATORY 0.2.6.1 ACUTE EXPOSURE o Inhalation of formaldehyde vapors at elevated concentrations may result in upper respiratory tract irritation and coughing. Severe exposure may result in serious lower respiratory effects, such as bronchitis, pulmonary edema, or pneumonia. Asthma may occur in susceptible individuals. o Respiratory distress and ARDS has been reported following ingestion or transdermal absorption of formaldehyde-containing compounds. NEUROLOGIC 0.2.7.1 ACUTE EXPOSURE o Lethargy and coma may occur following large ingestions or marked inhalation exposure. 0.2.7.2 CHRONIC EXPOSURE o Chronic exposure may result in malaise, headache, sleeping disturbances and irritability. GASTROINTESTINAL 0.2.8.1 ACUTE EXPOSURE o Nausea, vomiting, and severe abdominal pain may occur following ingestion. Corrosive gastritis, hematemesis, and edema and ulceration of the esophagus may occur. HEPATIC 0.2.9.1 ACUTE EXPOSURE o Hepatotoxicity has been associated with inhalation exposure in animals and suggested in humans, although hepatitis serologies were not preformed. o Hyperbilirubinemia has been reported following ingestion. o Biliary sclerosis occurred following formalin instillation into hydatid cyst. GENITOURINARY 0.2.10.1 ACUTE EXPOSURE o Nephritis and acute renal failure may occur. Membranous nephropathy has been associated with formaldehyde exposure. ACID-BASE 0.2.11.1 ACUTE EXPOSURE o Metabolic acidosis and hyperlactatemia may occur. HEMATOLOGIC 0.2.13.1 ACUTE EXPOSURE o Intravascular hemolysis has been reported in dialysis patients receiving doses of formaldehyde during treatment. DERMATOLOGIC 0.2.14.1 ACUTE EXPOSURE o Allergic dermatitis and rash may occur. IMMUNOLOGIC 0.2.19.1 ACUTE EXPOSURE o Antibodies to formaldehyde (Types I and II reactions) have been measured in exposed persons with clinical effects ranging from irritation to severe hypersensitivity reactions. Type IV reactions may result in allergic contact dermatitis. Immunologic reactions may be delayed by hours to months. o Bronchial asthma-like signs and symptoms have been reported. Evidence of formaldehyde sensitization or allergy causing true asthma is inconclusive. Respiratory effects do not consistently correlate with the development of formaldehyde-specific immunoglobulins. o Membranous nephropathy has been associated with immunologic reaction to suspected formaldehyde exposure. 0.2.19.2 CHRONIC EXPOSURE o Allergic contact dermatitis, eczema and other signs have been attributed to formaldehyde sensitivity. REPRODUCTIVE HAZARDS o Formaldehyde has not been shown definitely to be teratogenic in animals. Formaldehyde probably presents little or no risk as a potential human teratogen. o Menstrual disorders have been reported in women occupationally exposed to formaldehyde, but these results are controversial. In experimental animal studies, some effects on spermatogenesis have been reported. o Occupational exposure at recommended limits is not thought to present a reproductive risk. Formaldehyde exposure among female hospital workers did not correlate with an increase in spontaneous abortion in one study, but did correlate in another. 1. Low-birthweight children have been reported in female workers exposed to urea-formaldehyde resin, but studies are inconclusive. Formaldehyde appears to cross the placental barrier in mice. CARCINOGENICITY 0.2.21.2 HUMAN OVERVIEW o Formaldehyde is a probable human nasopharyngeal carcinogen (IARC 2A Limited evidence in humans and sufficient evidence in animals). 1. Occupational exposure to formaldehyde has been linked to the development of buccal and nasopharyngeal metaplasia/neoplasia, and to a lesser extent cancers of the nasal cavities. 2. Formaldehyde's role in lower respiratory tract cancer etiology has not been substantiated. Consensus on data collection and analysis methods will be necessary to evaluate the link between formaldehyde and lung cancer. 3. Formaldehyde reacts with HYDROGEN CHLORIDE to form BIS-CHLOROMETHYL ETHER, a known human carcinogen. GENOTOXICITY o Formaldehyde appears to be mutagenic. The basis for its genetic activity is its ability to form cross-links in DNA and proteins. LABORATORY: o FORMALDEHYDE PLASMA LEVELS are not clinically useful, but may help in dialysis monitoring. FORMIC ACID LEVELS are not useful for assessing exposure or adsorption. o Monitor acid base status in symptomatic patients. Monitor liver function tests. Monitor hematocrit and hemoglobin concentration in dialysis patients repeatedly exposed parenterally to formaldehyde. Monitor blood METHANOL levels after significant formalin ingestion. o Pulmonary function testing and nasal and bronchial provocation tests may be recommended following inhalation of formaldehyde. TREATMENT OVERVIEW: SUMMARY EXPOSURE o INHALATION EXPOSURE - 1. DECONTAMINATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer 100 percent humidified supplemental oxygen with assisted ventilation as required. 2. PULMONARY EDEMA (NONCARDIOGENIC): Maintain ventilation and oxygenation and evaluate with frequent arterial blood gas or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed. o DERMAL EXPOSURE - 1. DECONTAMINATION: Wash exposed area extremely thoroughly with soap and water. A physician may need to examine the area if irritation or pain persists. o EYE EXPOSURE - 1. DECONTAMINATION: Exposed eyes should be irrigated with copious amounts of tepid water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist, the patient should be seen in a health care facility. o ORAL EXPOSURE - 1. DILUTION: Following ingestion and/or prior to gastric evacuation, immediately dilute with 4 to 8 ounces (120 to 240 mL) of milk or water (not to exceed 15 mL/kg in a child). 2. Do NOT induce emesis. a. GASTRIC LAVAGE: Consider after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in Trendelenburg and left lateral decubitus position or by endotracheal intubation. Control any seizures first. (1) CONTRAINDICATIONS: Loss of airway protective reflexes or decreased level of consciousness in unintubated patients; following ingestion of corrosives; hydrocarbons (high aspiration potential); patients at risk of hemorrhage or gastrointestinal perforation; and trivial or non-toxic ingestion. 3. ACTIVATED CHARCOAL: Administer charcoal as slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old. 4. Monitor EKG and vital signs regularly. 5. Correct metabolic acidosis with intravenous sodium bicarbonate. Monitor blood gases to guide bicarbonate therapy. Monitor methanol levels if FORMALIN was ingested. 6. Hemodilaysis should be considered in those patients with severe acid-base disturbances refractory to conventional therapy, or in cases with significant methanol levels. 7. HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid, place in Trendelenburg position. If hypotension persists, administer dopamine (2 to 20 mcg/kg/min) or norepinephrine (0.1 to 0.2 mcg/kg/min), titrate to desired response. ORAL EXPOSURE o EMESIS: Induction of emesis is not recommended because of the potential for cardiovascular instability. o DILUTION: Following ingestion and/or prior to gastric evacuation, immediately dilute with 4 to 8 ounces (120 to 240 mL) of milk or water (not to exceed 15 mL/kg in a child). o After ingestion of concentrated formaldehyde, gastric lavage with a soft small-bore NG tube may facilitate removal without producing further trauma. Although no data on adsorption to activated charcoal could be found, it is suggested following lavage. o ACTIVATED CHARCOAL: Administer charcoal as slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old. o MONITOR EKG AND VITAL SIGNS regularly. o CORRECT METABOLIC ACIDOSIS with intravenous sodium bicarbonate. Monitor blood gases to guide bicarbonate therapy. Monitor methanol levels. o HEMODIALYSIS should be considered in those patients with severe acid-base disturbances refractory to conventional therapy, or in cases with significant methanol levels. o HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid, place in Trendelenburg position. If hypotension persists, administer dopamine (2 to 20 mcg/kg/min) or norepinephrine (0.1 to 0.2 mcg/kg/min), titrate to desired response. INHALATION EXPOSURE o DECONTAMINATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer 100 percent humidified supplemental oxygen with assisted ventilation as required. EYE EXPOSURE o DECONTAMINATION: Exposed eyes should be irrigated with copious amounts of tepid water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist, the patient should be seen in a health care facility. DERMAL EXPOSURE o DECONTAMINATION: Wash exposed area extremely thoroughly with soap and water. A physician may need to examine the area if irritation or pain persists. RANGE OF TOXICITY: o INGESTION of as little as 30 mL of a 37% solution of formaldehyde has resulted in death. ANTIDOTE AND EMERGENCY TREATMENT: Decontamination: Dilute with milk or water in alert patients as a first aid measure to reduce corrosive effects at scene. Follow with a bolus of charcoal (1 g/kg) and a mild saline cathartic. Elimination enhancement: Severe acidosis and deteriorating vital signs are indications for considering dialysis, but the literature does not contain adequate case studies to guide treatment. There are no antidotes. Supportive care: 1. Monitor electrolytes, fluids, acid-base, and kidney function closely. 2. Watch for signs of gastrointestinal hemorrhage and perforation with serial vital signs, abdominal examinations, and complete blood counts. 3. Check blood methanol levels and treat accordingly in formalin ingestions. 4. Fibrosis of stomach has required partial gastrectomy in the past. [Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 1003]**PEER REVIEWED** Irrigate eyes with water. Wash contaminated areas of body with soap and water. Gastric lavage (stomach wash), if swallowed, using 1% ammonium carbonate and followed by saline catharsis. Oxygen, if indicated. [ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988. 250]**PEER REVIEWED** ANIMAL TOXICITY STUDIES: EVIDENCE FOR CARCINOGENICITY: CLASSIFICATION: B1; probable human carcinogen. BASIS FOR CLASSIFICATION: Based on limited evidence in humans, and sufficient evidence in animals. Human data include nine studies that show statistically significant associations between site-specific respiratory neoplasms and exposure to formaldehyde or formaldehyde-containing products. An increased incidence of nasal squamous cell carcinomas was observed in long-term inhalation studies in rats and in mice. The classification is supported by in vitro genotoxicity data and formaldehyde's structural relationships to other carcinogenic aldehydes such as acetaldehyde. HUMAN CARCINOGENICITY DATA: Limited. ANIMAL CARCINOGENICITY DATA: Sufficient. [U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS) on Formaldehyde (50-00-0) Available from: http://www.epa.gov/ngispgm3/iris on the Substance File List as of March 15, 2000]**QC REVIEWED** A2. A2= Suspected human carcinogen. [American Conference of Governmental Industrial Hygienists. Threshold Limit Values (TLVs) for Chemical Substances and Physical Agents and BiologicalExposure Indices (BEIs) for 1995-1996. Cincinnati, OH: ACGIH, 1995. 22]**QC REVIEWED** Evaluation: There is limited evidence in humans for the carcinogenicity of formaldehyde. There is sufficient evidence in experimental animals for the carcinogenicity of formaldehyde. Overall evaluation: Formaldehyde is probably carcinogenic to humans (Group 2A). [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. 62 336 (1995)]**QC REVIEWED** NON-HUMAN TOXICITY EXCERPTS: INHALATION ... BY ANIMALS CAUSES PROMPT & SEVERE IRRITATION OF EYES & RESP TRACT. ... EDEMA & HEMORRHAGES OF ... LUNG, & SIGNS OF HYPEREMIA & PERIVASCULAR EDEMA IN THE LIVER AND KIDNEYS. [Patty, F. (ed.). Industrial Hygiene and Toxicology: Volume II: Toxicology. 2nd ed. New York: Interscience Publishers, 1963. 1970]**PEER REVIEWED** PROLONGED EXPOSURE OF RABBITS TO FORMALDEHYDE CAUSED ACID PHOSPHATASE, TWEEN-60-ESTERASE, NAPHTHOL-AS-D-ACETATE-ESTERASE, PROLINE-OXIDASE & HYDROXYPROLINE-2-EPIMERASE ACTIVITIES TO INCREASE & LEUCYL-AMINOPEPTIDASE & BETA-GLUCURONIDASE TO DECREASE. IT INDUCED BRONCHIAL CELL HYPERPLASIA WITH HYPERMUCIGENESIS, EXTRUSION OF BRONCHIAL CELLS, BRONCHIOLAR HYPERMUCIGENESIS, PARCELLARY SQUAMOUS METAPLASIA OR NECROBIOSIS OF EPITHELIA. [IONESCU J ET AL; MORPHOL EMBRYOL (BUCUR) 24 (3): 232-42 (1978)]**PEER REVIEWED** CD-1 MICE WERE GIVEN UP TO 185 MG/KG BODY WT FORMALDEHYDE BY GAVAGE ON DAYS 6-15 OF GESTATION. HIGHEST DOSE WAS ... TOXIC TO DAMS, BUT NO EMBRYOTOXICITY OR TERATOGENICITY WAS SEEN WITH ANY DOSE. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. V29 366 (1982)]**PEER REVIEWED** ACUTE ... EFFECTS ... IN RATS ... /& OTHER EXPTL ANIMALS/ TO LOW (LESS THAN 1 PPM) OR MODERATE (10-50 PPM) ... /OF/ VAPOR RESULTED IN INCREASED AIRWAY RESISTANCE, DECR SENSITIVITY OF NASOPALATINE NERVE, IRRITATION OF EYES & OF RESP SYSTEM, & CHANGES IN HYPOTHALAMUS. EXPOSURE TO HIGH DOSES (ABOVE 100 PPM) ... CAUSED SALIVATION, ACUTE DYSPNEA, VOMITING, CRAMPS & DEATH ... . [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. V29 364 (1982)]**PEER REVIEWED** EXPOSURE BY INHALATION FOR UP TO 90 DAYS PRODUCED INTERSTITIAL INFLAMMATION IN LUNGS OF DOGS, RATS, MONKEYS, RABBITS & GUINEA-PIGS. ... HAIR DEPIGMENTATION WAS OBSERVED IN BLACK MICE AT SITE OF SC INJECTION OF 100 UG FORMALDEHYDE. ... MICE TREATED WITH FORMALDEHYDE ON SKIN DEVELOPED SEVERE LIVER DAMAGE. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. V29 365 (1982)]**PEER REVIEWED** GROUPS OF 119-120 MALE & 120 FEMALE FISCHER 344 RATS, 7 WK OF AGE WERE EXPOSED TO 0, 2, 5.6 OR 14.3 PPM (0, 2.5, 6.9, 17.6 MG/CU M) ... GREATER THAN 97.5% PURE VAPOR BY WHOLE-BODY EXPOSURE FOR 6 HR/DAY ON 5 DAYS/WK FOR UP TO 24 MO, FOLLOWED BY 6 MO OBSERVATION PERIOD. ... LIFE-TABLE ANALYSIS OF ... DATA REVEALED SIGNIFICANT INCR (P < 0.0167) IN INCIDENCES OF SQUAMOUS-CELL CARCINOMAS IN /NASAL CAVITY OF RATS/ EXPOSED TO 14.3 PPM FORMALDEHYDE VAPOR; NO OTHER NEOPLASM WAS INCREASED SIGNIFICANTLY. THE INCIDENCE OF A VARIETY OF NON-NEOPLASTIC LESIONS WERE SIGNIFICANTLY INCREASED IN RATS EXPOSED TO FORMALDEHYDE. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. V29 361 (1982)]**PEER REVIEWED** GROUPS OF 6 MALE CYNOMOLGUS MONKEYS ... & 10 MALE & 10 FEMALE SYRIAN GOLDEN HAMSTERS WERE EXPOSED TO 0, 0.2, 1.0 OR 3 PPM (0, 0.24, 1.2 OR 3.7 MG/CU M) FORMALDEHYDE VAPOR (98.8% PURE) FOR 22 HR/DAY ON 7 DAYS/WK FOR 26 WK. SQUAMOUS METAPLASIA OF NASAL TURBINATES WERE EVIDENT IN 6/6 MONKEYS EXPOSED TO 3 PPM & IN 1/6 EXPOSED TO 1 PPM. ... NO EXPOSURE-RELATED EFFECTS WERE DEMONSTRATED IN HAMSTERS. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. V29 365 (1982)]**PEER REVIEWED** REPEATED INHALATION EXPOSURE TO VAPORS AT 15 PPM IN MALE CHARLES RIVER CD RATS & MALE C57BL6/F1 MICE WAS STUDIED. RATS WERE RELATIVELY INSENSITIVE TO IRRITANT ACTION WHILE MICE WERE MORE SENSITIVE, SHOWING COMPARABLE REDUCTION IN TIDAL VOL, BUT GREATER DECR IN RESPIRATORY RATE & MINUTE VOL. CARBON DIOXIDE PRODUCTION AS WELL AS BODY TEMP WERE DECR TO GREATER EXTENT IN MICE THAN IN RATS. [JAEGER RJ, GEARHART JM; TOXICOLOGY 25 (4): 299-309 (1982)]**PEER REVIEWED** With Salmonella typhimurium, the minimum concn required to induce 8-azaguanine resistance was 170 uM. [Goldmacher VS et al; Toxicol Epidemiol Mech (Pap Meet) 173-91 (1983)]**PEER REVIEWED** 15 ppm formaldehyde caused an initial wave of cell replication in the nasal cavity of mice and rats 18 hr after a 6 hr exposure. The /percentage/ of replicating cells remained ... elevated for 3-5 days and then began to decrease. Similar elevations occurred following 3 daily exposures to 6 ppm formaldehyde in rats, but not mice. ... [Swenberg JA et al; Toxicol Epidemiol Mech (Pap Meet) 225-36 (1983)]**PEER REVIEWED** ... Threshold concn of sensitization effect of /formaldehyde/ in guinea pigs was 0.5 mg/cu m. ... Quantitative changes were seen only in B-lymphocytes, whereas T-lymphocytes were essentially unchanged. At 3 mg/cu m the sensitization effect was seen in all the animals. The T-lymphocytes decreased substantially but B-lymphocytes increased. ... [Dueva LA; Gig Tr Prof Zabol 8: 20-3 (1983)]**PEER REVIEWED** ... Primary hamster embryo cells were treated by exposure to gaseous formaldehyde or by incorporation into the medium, a dose-related incr in the frequency of SA7 virus transformation was produced. ... Length of chemical treatment and the time interval before subsequent addition of transforming virus was critical, with 2 hr treatment times being most efficient. ... 2.2 ug/ml produced significantly enhanced viral transformation. ... [Hatch GG et al; Environ Mutagen 5 (1): 49-57 (1983)]**PEER REVIEWED** ... RATS /EXPOSED/ CONTINUOUSLY DURING PREGNANCY TO ... VAPORS (1 MG/CU M) ... /SHOWED/ NO VISIBLE FETAL MALFORMATIONS. ASCORBIC ACID CONTENT OF TREATED FETUSES WAS LOWER THAN CONTROLS BUT BODY WT WAS INCR. FETAL DNA CONTENT WAS DECR & RNA CONTENT WAS INCR. [Shepard, T.H. Catalog of Teratogenic Agents. 5th ed. Baltimore, MD: The Johns Hopkins University Press, 1986. 701]**PEER REVIEWED** GROUPS OF 100 MALE SPRAGUE-DAWLEY RATS WERE EXPOSED FROM 9 WK OF AGE TO (A) 14.3 PPM (17.44 MG/CU M) FORMALDEHYDE (PURITY UNSPECIFIED) & 10 PPM (16.2 MG/CU M) HYDROGEN CHLORIDE GAS BEFORE DILN IN EXPOSURE CHAMBER TO MAXIMIZE FORMATION OF BIS(CHLOROMETHYL)ETHER; (B) 14.1 PPM (17.2 MG/CU M) FORMALDEHYDE & 9.5 PPM 115.48 MG/CU M) HYDROGEN CHLORIDE NOT MIXED BEFORE INTRODUCTION INTO ... CHAMBER; (C)14.2 PPM (17.32 MG/CU M) FORMALDEHYDE VAPOR ALONE; (D) HYDROGEN CHLORIDE GAS ALONE (10.2 PPM); OR (E) AIR (SHAM-EXPOSED CONTROLS). AFTER ... 382 EXPOSURES OVER ... 588 DAYS (19.4 MO), 10 HISTOLOGICALLY CONFIRMED, GROSSLY VISIBLE NASAL SQUAMOUS-CELL CARCINOMAS WERE OBSERVED IN RATS EXPOSED TO FORMALDEHYDE ALONE; NONE WERE SEEN IN CONTROLS OR IN RATS EXPOSED TO HYDROGEN CHLORIDE ALONE ... COMBINED EXPOSURE TO FORMALDEHYDE & HYDROGEN CHLORIDE DID NOT PRODUCE STATISTICALLY SIGNIFICANT INCR IN INCIDENCE OF NASAL SQUAMOUS-CELL CARCINOMAS OVER THAT OBTAINED WITH FORMALDEHYDE ALONE. ... [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. V29 362 (1982)]**PEER REVIEWED** EXPOSURE OF CULTURED MONKEY KIDNEY CELLS TO 1-16 MMOL ... FOR 15 MIN RESULTED IN FORMATION OF SHORT RNA CHAINS; CONCN EQUAL TO OR GREATER THAN 2 MMOL PRODUCED COMPLETE INHIBITION OF THYMIDINE INCORPORATION & CELL GROWTH. ALMOST COMPLETE REVERSAL OF THESE EFFECTS WERE SEEN WITHIN 24 HR AFTER REMOVAL OF FORMALDEHYDE; SUCH RECOVERY WAS NOT ACCOMPANIED BY UNSCHEDULED DNA SYNTHESIS. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. V29 367 (1982)]**PEER REVIEWED** Addition of aroclor-induced post-mitochondrial supernatant reduced the mutagenicity of formaldehyde in the bacterial cells. [Goldmacher VS et al; Toxicol Epidemiol Mech (Pap Meet) 173-91 (1983)]**PEER REVIEWED** DNA-protein crosslinks have been formed in the nasal respiratory mucosa of Fischer-344 rats exposed for 3 hr to selected concentrations of (3)H- and (14)C-formaldehyde. ... In rats depleted of glutathione and exposed to 10 ppm of (3)H-formaldehyde and (14)C-formaldehyde, the (3)H/(14)C ratio of the fraction of the DNA that was crosslinked to proteins was significantly (39 + or - 6%) higher than that of the inhaled gas. This suggests an isotope effect, either on the formation of DNA-protein crosslinks by labeled formaldehyde or on the oxidation of labeled formaldehyde catalyzed by formaldehyde or aldehyde dehydrogenase. These results suggest that the residual (unoxidized) formaldehyde present in the nasal mucosa of rats exposed to (3)H- and (14)C-formaldehyde may be "enriched" in 3-formaldehyde relative to (14)C-formaldehyde which can bind to DNA resulting in an isotope ratio higher than that of the inhaled gas. The isotope effect on the oxidation of (3)formaldehyde and (14)C-formaldehyde suggests that previous estimates of the amount of formaldehyde covalently bound to nasal mucosal DNA may have been too large. [Heck HD, Casanova M; Toxicol Appl Pharmacol 89 (1): 122-34 (1984)]**PEER REVIEWED** Glutathione is required for the oxidation of formaldehyde to formate catalyzed by formaldehyde dehydrogenae. The effects of glutathione depletion on the mechanisms of labeling of macromolecules in the rat nasal mucosa and bone marrow by (3)H-formaldehyde and (14)C-formaldehyde were investigated. Male rats were exposed for 3 hr to atmosphere containing (3)H-formaldehyde and (14)C-formaldehyde at concentrations of 0.9, 2,4,6, or 10 ppm, 1 day after a single 3 hr preexposure to the same concentration of unlabeled formaldehyde. Two hours prior to the second exposure, the animals were injected either with phorone (300 mg/kg, ip) or with corn oil. The concentration of nonprotein sulfhydryls in the nasal respiratory mucosa of phorone-injected rats was decreased to 10% of that of corn oil-injected rats. The metabolic incorporation of (3)H-formaldehyde and (14)C-formaldehyde into DNA, RNA and proteins in the respirtory and olfactory mucosa and bone marrow (femur) was significantly decreased, and DNA-protein crosslinking was significantly increased in the respiratory mucosa of phorone injected relative to corn oil injected rats at all formaldehyde concentrations. DNA-protein crosslinks were not detected in the respiratory mucosa of corn oil injected rats at 0.9 ppm. Evidence was obtained for the formation of adducts of formaldehyde with the RNA from the nasal respiratory mucosa of phorone injected rats at concentrations above 0.9 ppm. Covalent binding of formaldehyde to macromolecules in the bone marrow was not detected. [Casanova M, Heck HD; Toxicol Appl Pharmacol 89 (1): 105-21 (1987)]**PEER REVIEWED** Fifty-five chemicals, including /formaldehyde/, were evaluated in the Charnoff/Kavloff developmental toxicity screen. All chemicals were administered by gavage to pregnant ICR/SIM mice on gestation day 8 through 12. The mice were allowed to deliver, and several neonatal growth and viability parameters were measured in the offspring. ... Of the 26 compounds reported in the literature to be teratogenic or embryotoxic in mice following oral administration, 24 were positive in the developmental toxicity screen. ... [Seidenberg JM, Becker RA; Teratog Carcinog Mut 7 (1): 17-28 (1987)]**PEER REVIEWED** ... In a plate assay with Salmonella typhimurium strain TA100 in the absence and presence of S9 mix, a weak mutagenic response was observed. Using the pre-incubation method, formaldehyde induced without S9 mix a 1.6-fold and with S9 mix a 2.7-fold increase of revertant numbers over controls. [Schmid E et al; Mutagen 1 (6): 427-31 (1986)]**PEER REVIEWED** Poisoning is characterized by severe abdominal pain which may be followed by collapse and death. In less severe cases, acute nephritis with oliguria may develop. Formaldehyde poisoning has been recorded in cattle placed in calving sheds which had been cleaned and disinfected shortly before with a 35% solution of this material, and after drinking from foot-rot treatment baths. The addition of formaldehyde as a preservative to milk has caused intoxiction in calves. The clinical signs recorded included recumbency, abdominal pain, salivation and diarrhea. Postmortem examination revealed severe gastrointestinal tract lesions. [Humphreys, D.J. Veterinary Toxicology. 3rd ed. London, England: Bailliere Tindell, 1988. 192]**PEER REVIEWED** The use of formalin for the treatment of foot-rot in sheep can give rise to keratinization of the interdigital skin if the solution employed is too concentrated or its application too frequent. In severe cases this may lead to bacterial infection of the feet and result in serious losses. [Humphreys, D.J. Veterinary Toxicology. 3rd ed. London, England: Bailliere Tindell, 1988. 192]**PEER REVIEWED** Alkaline elution was employed to study DNA damage in Chinese hamster ovary-Kl cells treated with a series of biotic and xenobiotic aldehydes. DNA cross-linking was measured in terms of the reduction in the effect of methyl methanesulphonate on the kinetics of DNA elution and was observed in cells treated with formaldehyde, acetaldehyde, methylglyoxal and malonaldehyde. Propionaldehyde, valeraldehyde, hexanal, and 4-hydroxynonenal produced DNA single strand breaks, or lesions which were converted to breaks in alkali. Both types of DNA damage occurred in cells exposed to malonaldehyde. These findings support the hypothesis of a carcinogenic effect of the aldehydic products (malonaldehyde, methylglyoxal, propionaldehyde, hexanal, 4-hydroxynonenal) released in biomembranes during lipid peroxidation. Acetaldehyde did not cause DNA breaks. [Marinari UM et al; Cell Biochem Funct 2 (4): 243-8 (1984)]**PEER REVIEWED** Two groups of 12 male Wistar rats received either 243 ppm of acetaldehyde or 5.7 ppm of formaldehyde for 8 hr a day, 5 days a week during 5 weeks. These levels represent three times the threshold limit values for these substances in Brazilian legislation. The animals were evaluated by pulmonary function tests before and after exposure to the pollutants. The data obtained from these rats were compared with those of 12 controls, housed in identical conditions for the same length of time but breathing normal air. The results showed an increase of the functional residual capacity, residual volume, total lung capacity and respiratory frequency in the rats exposed to acetaldehyde atmosphere. The animals exposed to formaldehyde did not present pulmonary function alterations when compared with the controls. The damage caused by acetaldehyde to the peripheral regions of the lung parenchyma, affecting small airways or altering pulmonary elastic properties, is discussed. [Saldiva PNH et al; J Appl Toxicol 5 (5): 288-92 (1985)]**PEER REVIEWED** A 1 year inhalation toxicity study was performed on male albino rats using 0.1, 1.0, or 10 ppm formaldehyde. The nasal mucosa of half the rats was damaged bilaterally by electrocoagulation; 20 to 26 hr after which the rats were subjected to the first 6 hr exposure of formaldehyde. The schedule for the exposures was 6 hr per day, 5 days a week for up to 52 weeks. Decreases in liver glutathione content were noted in rats with damaged noses after 13 weeks exposure. Moderate to severe rhinitis was accompanied by keratinized or nonkeratinized metaplastic respiratory epithelium in rats at the highest exposure levels with or without nasal damage. Growth retardation was observed in the animals with or without a damaged nose after 2 weeks exposure at 10 ppm formaldehyde. At lower exposure levels metaplastic respiratory epithelium occurred only in rats with a damage nasal mucosa, indicating a higher susceptibility of damage mucosa for the irritating and cytotoxic actions of formaldehyde. A more severe basal cell hyperplasia and more severe squamous metaplasia of the respiratory epithelium was noted in rats exposed to 1 ppm formaldehyde and subjected to electroagulation, compared to rats with an undamaged nose and 10 ppm exposure levels. Effects on the olfactory epithelium were exclusively found in animals treated with 10 ppm formaldehyde effects were more posterior in rats with damaged noses, perhaps due to an abnormal air flow pattern in the damaged nose. No adverse effects were seen at 0.1 or 1 ppm in rats with an intact nasal mucosa. The damaged rat nose is more susceptible than the undamaged to the cytotoxicity of formaldehyde, and even at a concentration of 10 ppm formaldehyde has no adverse effects on organs remote from the site of entry in rats with unchanged mucosa. [Appelman LM et al; J Appl Toxicol 8 (2): 85-90 (1988)]**PEER REVIEWED** The effects of benzo(a)pyrene and formaldehyde, alone and combined, on cell growth and DNA damage were determined in primary cultures of rat tracheal epithelial cells dissociated from rat tracheas. Cell cultures treated with 25 microm benzo(a)pyrene for 24 hr or 200 microM formaldehyde for 90 min did not have a marked reduction in cell growth. However, their combined treatment reduced cell growth by 60% of control when cultures were exposed to benzo(a)pyrene followed by formaldehyde as well as the reverse order. None of these treatments significantly decreased cell viability as judged by dye exclusion, nor did they enhance cell terminal differentiation as measured by cornified envelope formation. Alkaline elution analysis of DNA damage detected both DNA-protein corsslinks and DNA single strand breaks as a result of formaldfehyde treatment, whereas BAP treatment caused only single strand breaks. While formaldehyde induced single strand breaks were repaired within 2 hr, benzo(a)pyrene induced single strand breaks were detected 3 days after treatment. Combined treatment of cell cultures with benzo(a)pyrene followed by formaldehyde resulted in more single strand breaks than was obtained from either agent alone, but less DNA-protein crosslinks than was detected from formaldehyde alone. The increased number of single strand breaks obtained from this combined treatment may be related to the marked enhancement of carcinogenesis observed in earlier in vivo-in vitro studies. [Cosma GN et al; Mutat Res 201 (1): 161-8 (1988)]**PEER REVIEWED** The effect of formaldehyde inhalation on total cytochrome p450 in the lungs of Sprague-Dawley rats was assessed after single and repeated exposure to 0, 0.5, 3, and 15 ppm formaldehyde. Whole-body exposures were conducted exposure systems for 6 hr/day, 5 days/week, for periods of exposure of 1 day, 4 days, 12 weeks, or 24 weeks. Lung cytochrome p450 were mesured 18 hr after the end of exposure at each time point. There were not detectable levels of total lung p450 in any of the rats that received a single 6 hr exposure to all three formaldehyde doses, while control lung p450 levels were similar to that found for 4 day and 12 week control rats. After 4 days of repeated exposures, however, there was a highly significantly, reproducible, and dose-dependent increase in lung p450 levels relative to controls, with the 0.5, 3, and 15 ppm groups demonstrating 383, 1026, and 1123% of control values, respectively. Lung p450 levels remained elevated all formaldehyde concentrations through 12 and 24 weeks of exposure, although the percentage difference between exposed and control rats continually dropped throughout the course of long-term repeated exposures. While formaldehyde exposed rats did have decreased total body weight relative to controls, lung microsomal protein and lung weight of nearly all of the formaldehyde exposed rats was not significntly different from the controls. the initial inactivation of lung p450 after a single formaldehyde exposure is apparently a transient phenomenon, with dose-dependent induction of the total p450 levels in the lung as the pattern of response to repeated exposures to inhaled formaldehyde. [Dallas CE et al; Environ Res 49 (1): 50-9 (1989)]**PEER REVIEWED** Male Wistar rats were exposed to 0, 10 or 20 ppm formaldehyde vapor for 4, 8, or 13 weeks (6 hr/day; 5 days/week), and were then observed for periods up to 126 weeks. Transient growth retardation occurred in both test groups. Death rate was not noticably affected by formaldehyde. Despite recovery periods of at most 126 weeks, the nasal respiratory and olfactory epithelium of many rats of the 20 ppm group exhibited non-nooplastic histopathological changes. Similar but much less severe changes of the respiratory epithelium were seen in a small number of rats of the 10 ppm group; the olfactory epithelium was not visibly affected in rats of this group. Nasal tumours considered to be induced by formaldehyde were seen only in the 20 ppm group and mainly in rats that had been exposed for 13 weeks, the incidence being 4.5% (6/132). These tumours comprised 3 squamous cell carcinomas, 1 carcinoma in situ and 2 polypoid adenomas, all originating from respiratory epithelium. Rat nasal respiratory epithelium severely damaged by formaldehyde vapor ofter does not regenerate and in some cases develops tumours. [Feron VJ et al; Cancer Lett 39 (1): 101-11 (1988)]**PEER REVIEWED** Formaldehyde caused nasal squamous cell carcinomas in the rat following 2 year inhalation exposure. The incidence of this tumor in a historical data base of 16,794 rats was nil, indicating that it is a rare spontaneous tumor. Five different mathematical extrapolation models were applied to the rat nasal tumor data to produce estimates at 10(-4) risk (the size of the historical data base) of between 3.232 and 0.003 ppm formaldehyde depending on the model and choice of maximum likelihood estamate or lower confidence limit values. [Brown LP; Regul Toxicol Pharmacol 10 (2): 196-200 (1989)]**PEER REVIEWED** The effects of formaldehyde on mammalian respiratory ciliary function were studied in-vitro. Tracheal rings from New Zealand white rabbits were incubatd with 16, 33, or 66 ug/cu m formaldehyde for up to 60 minutes. Formaldehyde induced dose and time dependent decreases in the areas of ciliary activity and ciliary best frequency. The inhibition of ciliary functin was reversible, but the times for recovery increased with increasing formaldehyde concentration. Porcine tracheal rings were incubated with up to 66 ug/cu m formaldehyde for 60 minutes followed by up to 65 minutes recovery. The number of extractable active cilia (ciliary axonemes) was determined. Formaldehyde decreased the number of extractable ciliary axonemes and associated ATPase activity in a dose and time dependent manner. The inhibitory effects were reversible. [Hastie AT et al; Toxicol & Appl Toxicol 102 (2): 282-91 (1990)]**PEER REVIEWED** The induction of ornithine-decarboxylase activity and DNA synthesis was studied in the glandular stomach mucosa of rats afer gastric intubation of formaldehyde. Male Fischer rats were given doses of formaldehyde ranging from 11 to 110 mg/kg body weight by gastric intubation. The maximum increase in ornithine-decarboxylase activity was a 100 fold increase noted after 16 hours. The maximum increase in DNA synthesis was a 49 fold increase after 16 hours in the pyloric mucosa of the stomach. Even doses lower than 75 mg/kg, formaldehyde induced ornithine-decarboxylase activity and DNA synthesis in the pyloric mucosa. All the glandular stomach carcinogens and tumor promoters examined have been found to induce ornithine-decarboxylase activity and stimulate DNA synthesis in the glandular stomach mucosa. Inductions of ornithine-decarboxylase activity and DNA synthesis are useful markers of possible tumor promoting activity in the glandular stomach mucosa. [Furihata C et al; Japanese J of Cancer Res 79 (8): 917-20 (1988)]**PEER REVIEWED** The relative toxicities of formaldehyde and glutaraldehyde to the rat nasal epithelium were determined following intra-nasal instillation of aqueous solutions of these compounds into one nostril of male Fischer 344 (F-344) rats. Lesions identical in appearance to those resulting from acute inhalation exposure to formaldehyde were induced by both compounds in a concentration-dependent manner. While sterile saline and 10 mM glutaraldehyde induced no significant epithelial changes, 20 and 40 mM glutaraldehyde induced extensive lesions in the treated side of the nose. Aldehyde induced lesions included inflammation, epithelial hypertrophy, and squamous metaplasia in association with marked increases (2-8-fold) in labeling index for both compounds. Formaldehyde induced similar lesions but required concentrations of 200 mM or more to elicit a toxic response. Thus, glutaraldehyde is approximately an order of magnitude more toxic to the nasal epithelium than formaldehyde. [St Clair M BG et al; Toxicol Pathol 18 (3): 353-61 (1990)]**PEER REVIEWED** Male and female Sprague-Dawley rats of different ages at the start of the experiments (12 day embryos, and 7 and 25 weeks old) were administered formaldehyde in drinking water at different doses (2,500 or 1,500, 1,000, 500, 100, 50, 10, 0 ppm). An increased incidence of leukemias and of gastro-intestinal tumors was observed in formaldehyde treated rats. Gastro-intestinal tumors are exceptionally rare in the rats of the colony used. [Soffritti M et al; Toxicol Ind Health 5 (5): 699-730 (1989)]**PEER REVIEWED** The effects of formaldehyde on the respiratory tract were studied in monkeys. Male rhesus monkeys were exposed to 6 ppm formaldehyde 6 hours/day, 5 days/week for 1 or 6 weeks. Histopathological changes induced by formaldehyde included mild degeneration and early squamous metaplasia in the transitional and respiratory epithelium of the nasal passages and the respiratory epithelium of the trachea and bronchi. There was little difference in the severity of the nasal lesions between animals exposed for 1 or 6 weeks; however, the percentage of nasal mucosal epithelial area with lesions was significantly larger in monkeys exposed for 6 weeks. Only minimal histopathological changes occurred in the lower airways. No treatment related effects were seen in the maxillary sinuses or nonrespiratory ortans. Thymidine labeling indices were significantly increased in the respiratory epithelium of the nasal passages at both 1 and 6 weeks. The areas of greatest proliferation corresponded to the areas of the lesions. Labeling indices in the trachea and carina were significantly elevated after 1 week of exposure. They were nonsignificantly elevated in the transitional and olfactory epithelium of the nasasl passages. Formaldehyde induced nasal lesions are more widespread in the monkey than in the rat, and monkeys are more sensitive to the acute and subacute effects of formaldehyde. [Monticello TM et al; Am J Path 134 (3): 515-27 (1989)]**PEER REVIEWED** A 28 month inhalation study was carried out in male SPF reared albino Wistar rats to determine the significance of electrocoagulation damage for the induction of nasal tumors by formaldehyde vapor. Male rats with severely damaged or undamaged noses were exposed 6 hours/day, 5 days/week for 28 months to formaldehyde at concentrations of 0.0, 0.1, 1.0, and 10 ppm. Degenerative, inflammatory and hyperplastic changes were noted in the nasal respiratory and olfactory mucosa in rats with intact noses at the highest dose levels. The incidence of formaldehyde induced rhinitis, hyperplasia and metaplasia of the respiratory epithelium, and degeneration and hyperplasia and metaplasia of the olfactory epithelium all occurred in increased numbers in rats exposed to formaldehyde with damage nasal passages. The incidence of nasal tumors in animals with damage nasal mucosa and treated with 10 ppm formaldehyde for 28 months was 29% (17 of 58 rats), while in the group of rats with an intact nasal mucosa exposed to 10 ppm formaldehyde for 28 months, only 1 of 26 (4%) developed a nasal tumor. Increased tumor incidences were not oberved in rats with damaged nasal mucosa exposed to 0.1 or 1.0 ppm formaldehyde for 28 months or to 0.1, 1.0, or 10 ppm formaldehyde for 3 months. The condition of the nasal mucosa is an important factor in the development of nasal tumors among rats exposed to formaldehyde. [Woutersen RA et al; J Appl Toxicol 9 (1): 39-46 (1989)]**PEER REVIEWED** Male and female Wistar rats were given formaldehyde solution in their drinking water at concentrations of 0.50, 0.10, 0.02 and 0% for 24 months. Significant decreases in body weight and food and water intake were observed in the 0.50% group of both sexes and all rats in this group died by 24 months. Various non-neoplastic lesions were observed in rats, mostly in the 0.50% group. In this group, erosions and/or ulcers were evident in both the forestomach and glandular stomach. In the forestomach, squamous cell hyperplasia with or without hyperkeratosis and downward growth of basal cells were observed. Glandular hyperplasia of the fundic mucosa was noted along the limiting ridge. A few of such changes of the upper GI tract were seen in the 0.10% group. No toxicological abnormalities were found in 0.02% group of both sexes. There were no significant differences in the incidences of any tumors among groups of both sexes. Based on these findings, the no observable effect level of formaldehyde was 0.02% in the drinking water (10 mg/kg body wt/day). [Tobe M et al; Toxicol 56 (1): 79-86 (1989)]**PEER REVIEWED** The effects of intermittent and continuous inhalation exposure to formaldehyde were studied in rats. Male Wistar rats were exposed to 0, 1, or 2 ppm formaldehyde continuously for 8 hours a day, 5 days a week for 13 weeks. Other rats were exposed to 0, 2, or 4 ppm formaldehyde intermittently, for eight 30 minute exposures separated by 30 mintue periods of nonexposure, 5 days a week for 13 weeks. After 13 weeks, the nasal cavity tissues were examined for histopathological changes. Formaldehyde did not significantly affect body weight again. A slight nonsignificant increase in cell turnover was seen after 3 days in rats exposed intermittently to 2 ppm or continuously to 1 ppm formaldehyde. This effect was not seen after 13 weeks. Treatment related histopathological changes were seen only in nasal tissues from rats exposed intermittently to 4 ppm formaldehyde. These consisted of disarrangement, hyperplasia, and squamous metaplasia with or without keratinization of the respiratory epithelium of the septum and nasoturbinates. These changes were not seen in rats exposed continuously to 2 ppm formaldehyde, which produced the same total daily dose as the intermittent 4 ppm exposure group. Under conditions of formaldehyde, exposure concentration, not total dose, determines the severity of the cytotoxic effects. [Wilmer JWGM et al; Toxicol Letters 47 (3): 287-93 (1989)]**PEER REVIEWED** Sprague-Dawley rats were exposed to 0, 5, 10, 20 or 40 ppm formaldehyde for 6 hr/day from day 6 to 20 of gestation. On day 21 of gestation, no effect on embryonic or fetal lethality, nor significant alterations in the external, visceral or skeletal appearance of the fetuses were noted in any of the exposed groups. Significant concentrations-related reduction of fetal body weight occurred at 20 and 40 ppm, and at 40 ppm fetal body weights were 20% less than those of the controls. Maternal toxicity, indicated by significant reduction in body weight and absolute weight gain, was observed at 40 ppm. Formaldehyde is slightly fetotoxic at 20 ppm. Neither embryolethal nor teratogenic effects were observed following inhalation exposure at levels up to 40 ppm. [Saillerfait AM et al; Food Chem Toxicol 27 (8): 545-8 (1989)]**PEER REVIEWED** NON-HUMAN TOXICITY VALUES: LD50 Rat oral 800 mg/kg [ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988. 249]**PEER REVIEWED** LD50 Rat sc 420 mg/kg [ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988. 249]**PEER REVIEWED** LD50 Mouse sc 300 mg/kg [ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988. 249]**PEER REVIEWED** LD50 Guinea pig oral 260 mg/kg [ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988. 249]**PEER REVIEWED** ECOTOXICITY VALUES: LC50 Striped bass larvae 10 mg/l/48-96 hr; static bioassay. [Environmental Canada; Tech Info for Problem Spills: Formaldehyde p.67 (1985)]**PEER REVIEWED** Median lethal dose Rainbow trout (Salmo gairdneri) 50 mg/l/48 hr. /Conditions of bioassay not specified/ [Environment Canada; Tech Info for Problem Spills: Formaldehyde p.68 (1985)]**PEER REVIEWED** LC50 Flounder 100-300 mg/l/48 hr (aerated salt water) /Conditions of bioassay not specified/ [Environment Canada; Tech Info for Problem Spills: Formaldehyde p.70 (1985)]**PEER REVIEWED** LC50 Rainbow trout (Salmo gairdnerii) (green egg) 565 mg/l/96 hr static bioassay [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983. 680]**PEER REVIEWED** LC50 Rainbow trout (Salmo gairdnerii) (eyed egg) 198 mg/l/96 hr static bioassay [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983. 680]**PEER REVIEWED** LC50 Rainbow trout (Salmo gairdnerii) (sac larvae) 89.5 mg/l/96 hr static bioassay [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983. 680]**PEER REVIEWED** LC50 Rainbow trout (Salmo gairdnerii) fingerlings 61.9 mg/l/96 hr static bioassay [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983. 680]**PEER REVIEWED** LC50 Rainbow trout (Salmo gairdnerii) 440 mg/l/96 hr static bioassay [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983. 680]**PEER REVIEWED** LC50 Rainbow trout (Salmo gairdnerii) 214 mg/l/24 hr static bioassay [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983. 680]**PEER REVIEWED** LC50 Rainbow trout (Salmo gairdnerii) 118 ul/l/96 hr flow-through bioassay [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983. 680]**PEER REVIEWED** LC50 Atlantic salmon (Salmo salar) 173 ul/l/96 hr flow-through bioassay [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983. 680]**PEER REVIEWED** LC50 Lake trout (Salvelinus namaycush) 100 ul/l/96 hr flow-through bioassay [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983. 680]**PEER REVIEWED** LC50 Black bullhead (Ameiurus melas or Ictalurus melas) 62.1 ul/l/96 hr flow-through bioassay [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983. 680]**PEER REVIEWED** LC50 Channel catfish (Ictalurus punctatus) 65.8 ul/l/96 hr flow-through bioassay [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983. 680]**PEER REVIEWED** LC50 Green sunfish (Lepomis cyanellus) 173 ul/l/96 hr flow-through bioassay [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983. 680]**PEER REVIEWED** LC50 Bluegill (Lepomis macrochirus) 100 ul/l/96 hr flow-through bioassay [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983. 680]**PEER REVIEWED** LC50 Smallmouth bass (Micropterus dolomieui) 136 ul/l/96 hr flow-through bioassay [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983. 680]**PEER REVIEWED** LC50 Largemouth bass (Micropterus salmoides) 143 ul/l/96 hr flow-through bioassay [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983. 680]**PEER REVIEWED** LC50 Pimephales promelas (fathead minnow) 24.1 mg/l/96 hr (confidence limit 22.6 - 25.7 mg/l), flow-through bioassay with measured concentrations, 21.7 deg C, dissolved oxygen 7.4 mg/l, hardness 50.8 mg/l calcium carbonate, alkalinity 37.0 mg/l calcium carbonate, and pH 6.8. [Geiger D.L., D.J. Call, L.T. Brooke. (eds.). Acute Toxicities of Organic Chemicals to Fathead Minnows (Pimephales- Promelas). Vol. V. Superior WI:University of Wisconsin-Superior, 1990. 31]**PEER REVIEWED** TSCA TEST SUBMISSIONS: Chronic toxicity and oncogenicity were evaluated in male and female Fischer 344 rats (120/sex/dose level, 240/sex controls) exposed to formaldehyde by inhalation at 0, 2, 6 or 15 ppm for 6 hrs/day, 5 days/week, for 24 months. A total of 95 confirmed cases of nasal squamous cell carcinoma were observed in rats exposed to the highest dose level, 3 cases were observed in rats exposed to 6 ppm, and no cases were observed at the 2 ppm dose level or in controls. Further results from this study were not reported in this progress report.[Chemical Industry Institute of Toxicology; Progress Report on CIIT Formaldehyde Studies. (1980), EPA Old Document No. 44004, Fiche No. OTS0507060 ] **UNREVIEWED** Chronic toxicity and oncogenicity were evaluated in male and female B6C3F1 mice (120/sex/dose level, 240/sex controls) exposed to formaldehyde by inhalation at 0, 2, 6 or 15 ppm for 6 hrs/day, 5 days/week, for 24 months. A total of 2 confirmed cases of nasal squamous cell carcinoma were observed in mice exposed to the highest dose level and no cases were observed at the 2 or 6 ppm dose levels or in controls. Further results from this study were not reported in this progress report.[Chemical Industry Institute of Toxicology; Progress Report on CIIT Formaldehyde Studies. (1980), EPA Old Document No. 44004, Fiche No. OTS0507060 ] **UNREVIEWED** The effects of acute oral exposure to formaldehyde by gavage in male Wistar rats (20 in control group (water), 5/treated group, number of treated groups not reported) were determined. Formaldehyde (100 or 200 mg/kg) was administered in a single dose and the rats were necropsied on the 11th day following dosing. There were differences between treated and control animals at the highest does level in the following: increase in sperm head count, and a highly significant increase in the percentage of abnormal sperm heads, including straight heads (i.e. no hook), excessive curvature of heads, folded, coiled, thin or amorphous heads. There were no significant differences between treated and control animals in the following: clinical observations, histopathology of the testes, and testes weights.[Shell Oil Co.; The Effects of Acute Exposure of Dimethoxyethyl Phthalate, Glycerol Alpha-monochlorohydrin, Epichlorohydrin, Formaldehyde and Methylmethanesulfonate Upon Testicular Sperm in the Rat. (1982), EPA Document No. 878210077, Fiche No. OTS206200 ] **UNREVIEWED** METABOLISM/PHARMACOKINETICS: METABOLISM/METABOLITES: RAPID OXIDN OF FORMALDEHYDE INTO FORMATE FOLLOWED BY FURTHER OXIDN TO CARBON DIOXIDE TAKES PLACE PRINCIPALLY IN ERYTHROCYTES & LIVER. [The Chemical Society. Foreign Compound Metabolism in Mammals Volume 3. London: The Chemical Society, 1975. 339]**PEER REVIEWED** WHEN FEMALE RATS WERE ADMIN (14)C-FORMALDEHYDE IP AT DOSE LEVEL OF 70 MG/KG, 82% OF DOSE WAS EXPIRED AS (14)CARBON DIOXIDE & 13-14% WAS EXCRETED VIA KIDNEYS IN FORM OF METHIONINE, SERINE, & FORMALDEHYDE-CYSTEINE ADDUCT. [The Chemical Society. Foreign Compound Metabolism in Mammals Volume 3. London: The Chemical Society, 1975. 340]**PEER REVIEWED** Rats injected ip with 0.26 mg/kg (14)C-labeled formaldehyde ... excreted approx 22% of this dose in the urine over 5 days. Formic acid and a thiazolidine-4-carboxylic acid derivative were identified in urine as formaldehyde metabolites. [Hemminki K; Chem-Biol Interact 48 (2): 243-8 (1984)]**PEER REVIEWED** SHORTLY AFTER IV INJECTION OF 35 MG/KG FORMALDEHYDE, INTO DOGS, THERE WAS NO INCR IN PLASMA FORMALDEHYDE CONCN, BUT BIG INCR IN FORMIC ACID CONCN. ... THE RATE OF FORMALDEHYDE OXIDN IS COMPARABLE IN SEVERAL SPECIES OF MAMMALS ... [The Chemical Society. Foreign Compound Metabolism in Mammals Volume 3. London: The Chemical Society, 1975. 339]**PEER REVIEWED** A novel modification for urinary formic acid analysis was developed in order to gain experience in the biological monitoring of farmers exposed to the acid vapors in silage making. It appeared that the farmers excreted varying amounts of acid before the actual silage making period, but all showed increased excretion rates up to 15 hr after the exposures. The data indicated that formic acid may have a long biological half-life possibly causing an accumulation of the acid in the body. This might constitute unappreciated toxicological hazard, as the acid is an inhibitor of oxygen metabolism. [Liesivuori J; Ann Occup Hyg 30 (3): 329-34 (1986)]**PEER REVIEWED** The effect of deuterium substitution on the metabolism of formaldehyde and formate to carbon dioxide in vivo was examined. Four groups of male Sprague-Dawley rats were injected ip with (14)C labeled formaldehyde, formaldehyde-d2, sodium formate, or sodium formate-d at doses of 0.67 mmol/kg. Similar rates of labeled carbon dioxide exhalation were observed for the four groups of animals, the cumulative excretion of (14)Carbon dioxide in breath reaching 68-71% of the theoretical value 12 hr after injection in all cases. Plots of amount remaining to be excreted showed that the metabolism was biexponential, with half-lives of approximately 0.4 and 3 hr for the two phases for each of the four compounds. ... [Keefer LK et al; Drug Metals Dispos 15 (3): 300-4 (1987)]**PEER REVIEWED** Homogenates of respiratory and olfactory tissue from the rat nasal cavity were examined for their capacity to catalyze the NAD(+)-dependant oxidation of formaldehyde (in the presence and absence of glutathione) and of acetaldehyde. Both aldehydes were oxidized efficiently by nasal mucosal homogenates, and formaldehyde dehydrogenase and aldehyde dehydrogenase were tentatively identified in both tissue samples. At least two isoenzymes of aldehyde dehydrogenase differing either with respect to their apparent Km and max values with acetaldehyde as substrate, were found in the nasal mucosa, one of which may catalyze the oxidation of both formaldehyde and acetaldehyde. ... Repeated exposures of rats to formaldehyde (15 ppm, 6 hr/day, 10 days) or to acetaldehyde (1500 ppm, 6 hr/day, 5 days) did not substantially affect the specific activities of formaldehyde dehydrogenase and aldehyde dehydrogenase in nasal mucosal homogenates. Glutathione is a cofactor for formaldehyde dehydrogenase; the concentration of nonprotein sulfhydryls in respiratory mucosal homogenates was approximately 2.8 uM/g and was not changed significantly by repeated exposures to formaldehyde (15 ppm, 6 hr/day, 9 days). These data indicate that the rat nasal mucosa, which is the major target site for both aldehydes in inhalation toxicity studies, can metabolize both formaldehyde and acetaldehyde, and that the specific activities of formaldehyde and aldehyde dehydrogenase in homogenates of the nasal mucosa are essentially unchanged following repeated exposures to toxic concentrations of either compound. [Casanova-Schmitz M et al; Biochem Pharmacol 33 (7): 1137-42 (1984)]**PEER REVIEWED** The movement of blood formaldehyde in rabbits that were intoxicated with methanol has been investigated. When methanol alone was administered to rabbits orally, formaldehyde could not be detected in the blood. Further, in an experiment on the metabolism of methanol in vitro, formaldehyde was not detected in specimen samples but formate was. In contrast, when methanol was orally administered to rabbits that had been pretreated with diethyldithiocarbamate, an aldehyde dehydrogenase inhibitor, 17 to 33 microM of formaldehyde were detected in the blood 4 hours later. However, formaldehyde was not detected in the blood when methanol was orally administered to rabbits that had been pretreated with pyrazole, and alcohol dehydrogenase, inhibitor. After rabbits were given an intravenous administration of formaldehyde, and on the addition of formaldehyde to a rabbit liver homogenate and blood, the formaldehyde in both instances was metabolized rapidly. Formaldehyde that was not metabolized within 10 to 15 minutes, however, bound to the tissue proteins. Formaldehyde was seen to be rapidly metabolized to formate without accumulating in the blood or binding to the tissue proteins. [Matsumoto K et al; Nippon Hoigaku Zasshi 44 (3): 205-11 (1990)]**PEER REVIEWED** ABSORPTION, DISTRIBUTION & EXCRETION: ... ABSORBED FROM ALIMENTARY & RESP TRACTS. [Thienes, C., and T.J. Haley. Clinical Toxicology. 5th ed. Philadelphia: Lea and Febiger, 1972. 179]**PEER REVIEWED** IN RATS & MICE ADMIN (14)C-FORMALDEHYDE INTRAGASTRICALLY, 40% OF DOSE ... /WAS/ EXPIRED AS CARBON DIOXIDE, 10% /WAS/ EXCRETED IN URINE & 1% IN FECES AFTER 12 HR; CARCASSES CONTAINED 20% AFTER 24 HR & 10% AFTER 4 DAYS. WHEN FEMALE RATS WERE ADMIN (14)C-FORMALDEHYDE IP AT DOSE LEVEL OF 70 MG/KG, 82% OF DOSE WAS EXPIRED AS (14)CARBON DIOXIDE & 13-14% WAS EXCRETED VIA KIDNEYS ... . [The Chemical Society. Foreign Compound Metabolism in Mammals Volume 3. London: The Chemical Society, 1975. 340]**PEER REVIEWED** Less than 1% of the /skin/ applied dose of (14)C /as formaldehyde/ was excreted or concn in the major organs of the monkey. Approx 10 times this amt was found in the rat and guinea pig excreta and internal organs. ... The skin of the monkey was much less permeable to formaldehyde than that of rodents. A significant proportion ... was found after 72 hr at the site of application, in the skin and fur, and ... for rodents ... in the remaining carcass. [Jeffcoat AR et al; Chem Ind Inst Toxicol Conf on Formaldehyde Toxicol p.38-50 (1983)]**PEER REVIEWED** Airborne (14)C-labeled formaldehyde was primarily absorbed in the upper respiratory tract of rats, leading to a very high radioactive concn in the nasal mucosa. ... [Heck HD et al; Chem Ind Inst Toxicol, Conf on Formaldehyde Toxicol p.26-37 (1983)]**PEER REVIEWED** The effect of subchronic exposure to formaldehyde on blood formaldehyde concentrations was studied in monkeys. Young adult Rhesus monkeys were exposed to 0 or 6.00 ppm formaldehyde vapor 6 hours per day, 5 days per week for 4 weeks. Blood samples were obtained at 7 minutes and at 45 hours after the last exposure. The average blood formaldehyde concentrations obtained 7 minutes and 45 hours after exposure were 1.84 and 2.04 ug/g, respectively. The average blood formaldehyde concentraton in the controls was 2.42 ug/g. None of the concentrations were statistically different from each other. Subchronic exposure to a relatively high concentration of formaldehyde does not significantly increase the blood formaldehyde concentration of Rhesus monkeys. This result agrees with those of previous studies in rats and humans. Because formaldehyde is rapidly metabolized it does not accumulate in the blood or produce toxic effects at distant sites. The concentration of endogenous formaldehyde in the blood of Rhesus monkeys is similar to that of humans. [Casanova M et al; Food and Chem Toxicol 26 (8): 715-6 (1988)]**PEER REVIEWED** BIOLOGICAL HALF-LIFE: ... IN SEVERAL SPECIES ... FORMALDEHYDE HAS HALF-LIFE OF ONLY 1 MIN; BUT THE HALF-LIFE FOR FORMIC ACID IS SPECIES DEPENDENT. [The Chemical Society. Foreign Compound Metabolism in Mammals Volume 3. London: The Chemical Society, 1975. 339]**PEER REVIEWED** MECHANISM OF ACTION: ... Formaldehyde forms DNA adducts and DNA protein crosslinks in the rat nasal mucosa at 15 ppm. [Heck HD, Casanova-Schmitz M; Chem Ind Inst Toxicol, Conf on Formaldehyde Toxicol p.211-23 (1983)]**PEER REVIEWED** Human lymphoblast mutants at the X-linked hprt locus have been examined by Southern blot, Northern blot and DNA sequence analysis. A previous study had shown that approximately a third of the spontaneously arising mutants and half those induced by formaldehyde showed no alteration in restriction fragment pattern and thus were classified as point mutation. In this report, these point mutants fall into 4 catagories: normal size and amount of RNA, normal size but reduced amounts, reduced size RNA or no RNA. Sequence analyses of cDNAs prepared from hprt mRNAs were performed on 1 spontaneous and 7 formaldehyde induced mutants were base substitutions, all of which occurred at AT base-pairs. There was an apparent hot spot, in that 4/6 independent mutants were AT----CG transversions at one specific site. The remaining mutant had lost exon 8. [Liber HL et al; Mutat Res 226 (1): 31-7 (1989)]**PEER REVIEWED** INTERACTIONS: MICE EXPOSED TO 11 COMBINATIONS OF ACROLEIN-FORMALDEHYDE; RESPIRATORY RATE MONITORED & RESULTS INDICATE COMPETITIVE AGONISM BETWEEN ACROLEIN & FORMALDEHYDE. [KANE LE, ALARIE Y; AM IND HYG ASSOC J 39 (4): 270-4 (1978)]**PEER REVIEWED** /IN GUINEA PIGS/ 1 HR EXPOSURE TO CONCN OF 0.3 PPM & ABOVE PRODUCED INCR IN PULMONARY FLOW RESISTANCE ACCOMPANIED BY LESSER DECREASE IN COMPLIANCE. ... THE RESPONSE ... POTENTIATED BY SIMULTANEOUS ADMIN OF ... SODIUM CHLORIDE AEROSOL OF SUBMICRON PARTICLES. THE VALUES FOR PULMONARY RESISTANCE REMAINED ABOVE PREEXPOSURE LEVELS FOR 1 HR AFTER THE END OF EXPOSURE WHEN THE GAS-AEROSOL COMBINATION WAS USED. THIS PROLONGED RESPONSE ... SUGGEST THAT THE POTENTIATION IS BROUGHT ABOUT BY THE ATTACHMENT OF FORMALDEHYDE TO THE PARTICLES TO FORM AN IRRITANT AEROSOL. THIS ... IS FURTHER SUPPORTED BY FACT THAT WHEN 3, 10 & 30 MG/CU M CONCN OF SODIUM CHLORIDE WERE USED, THE POTENTIATION INCR WITH INCREASING CONCENTRATION OF PARTICLES. THE RESPONSE TO A GIVEN CONCN OF FORMALDEHYDE PLUS AEROSOL BREATHED BY NOSE WAS GREATER THAN THE RESPONSE TO THE GAS ALONE BREATHED THROUGH A TREACHEAL CANNULA. [Amdur, M.O., J. Doull, C.D. Klaasen (eds). Casarett and Doull's Toxicology. 4th ed. New York, NY: Pergamon Press, 1991. 867]**PEER REVIEWED** C3H/10T1/2 cells were treated with N-methyl-N'-nitro-N-nitrosoguanidine then repeatedly exposed to /formaldehyde/ (0.1-2.0 ug/ml). Exposure of N-methyl-N'-nitro-N-nitrosoguanidine initiated cultures to /formaldehyde/ of 0.5 or 1.0 ug/ml in a variety of treatment regimens resulted in focus formation in up to 9% of the treated dishes. Transformed foci were observed in < 2% of the cultures treated N-methyl-N'-nitro-N-nitrosoguanidine or /formaldehyde/ alone. Formaldehyde ... appears to be only a weak tumor promotor for C3H/10T1/2 cell transformation. [Frazelle JH et al; Cancer Res 43 (7): 3236-9 (1983)]**PEER REVIEWED** A study was performed on four groups of Sprague-Dawley rats: one exposed to wood dust (25 mg/cu m), another to formaldehyde (12.4 ppm) and a third to both wood dust and formaldehyde; the fourth group served a control group. After 104 weeks of exposure the nose and lungs were examined histologically. One well differentiated squamous cell carcinoma was found in the formaldehyde group. Squamous cell metaplasia was found significantly more often among the formaldehyde exposed rats. Squamous cell metaplasia with dysplasia was most frequently observed, however, in the group exposed to both formaldehyde and wood dust. There were also significantly more rats with pulmonary emphysema in the groups exposed to wood dust than in the other groups. [Holmstrom M et al; Acta Otolaryngol 108 (3-4): 274-83 (1989)]**PEER REVIEWED** The combined effects on the nasal epithelium of mixtures of ozone and formaldehyde at cytotoxic and noncytotoxic concentrations were examined. Male Wistar rats were exposed by inhalation during 22 hr/day for 3 consecutive days to 0.3, 1.0 or 3.0 ppm formaldehyde or to 0.2, 0.4, or 0.8 ppm ozone, or they were sham exposed to clean air. Treatment related histopathological nasal changes, such as dissarrangement, loss of cilia, and hyper/metaplasia of the epithelium were seen at 0.2, 0.4, and 0.8 ppm ozone and at 3 ppm formaldehyde. Simultaneous exposure to both materials did not noticeable affect type, degree, and size the microscopic nasal lesions. [Reuzel P GJ et al; J Toxicol Environ Health 29 (3): 279-92 (1990)]**PEER REVIEWED** PHARMACOLOGY: THERAPEUTIC USES: Disinfectants; Fixativ