Formaldehyde Studies on Kidneys

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.