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Comparison of the hypocholesterolemic effects of dietary soybean protein with those of formaldehyde-treated casein in rabbits.

Treatment of casein with formaldehyde changes its tertiary structure and decreases its hypercholesterolemic properties in rabbits. To investigate whether formaldehyde-treated casein exerts this hypocholesterolemic effect in the same manner as soybean protein, rabbits were fed high or low cholesterol diets containing soybean protein, casein, formaldehyde-treated casein or a mixture of casein and formaldehyde-treated casein. Formaldehyde-treated casein was hypocholesterolemic when fed in a low, but not in a high, cholesterol diet. The hypocholesterolemic effect of soybean protein was independent of the amount of cholesterol included in the diet. In contrast to rabbits fed soybean protein, steroid absorption in those fed formaldehyde-treated casein did not differ from that in rabbits fed native casein. Furthermore, the absorption of phosphorus and nitrogen was lower in rabbits fed formaldehyde-treated casein than in those fed native casein, whereas the absorption found in rabbits fed soybean protein resembled that of their casein-fed counterparts. The diets containing soybean protein and formaldehyde-treated casein produced a comparable ratio of lysine to arginine in serum. The results presented in this paper indicate that the hypocholesterolemic action of dietary formaldehyde-treated casein does not resemble that of soybean protein.

Amino Acids↗

Mortality from lymphohematopoietic malignancies among workers in formaldehyde industries.

BACKGROUND: Many U.S. factory workers are exposed to formaldehyde. Although increased risks for leukemia have been found in medical workers and other professionals exposed to formaldehyde, studies in industrial workers, who are thought to have higher exposures, have shown inconsistent associations. We extended follow-up of a cohort of industrial workers to evaluate the association between formaldehyde exposure and lymphohematopoietic cancers. METHODS: The cohort consisted of 25 619 workers (865 708 person-years) employed before January 1, 1966, at one of 10 U.S. industrial plants and followed through December 31, 1994. We analyzed formaldehyde exposure (peak exposure, average exposure intensity, cumulative exposure, and duration of exposure) and mortality from lymphohematopoietic malignancies using standardized mortality ratios and relative risks and 95% confidence intervals (CIs) based on Poisson regression. Statistical tests were two-sided. RESULTS: Among the cohort, there were 178 deaths from lymphohematopoietic malignancies. Relative risks for leukemia (69 deaths), particularly for myeloid leukemia (30 deaths), increased with formaldehyde exposure. Compared with workers exposed to low peak levels of formaldehyde (0.1-1.9 ppm), relative risks for myeloid leukemia were 2.43 (95% CI = 0.81 to 7.25) and 3.46 (95% CI = 1.27 to 9.43) for workers exposed to peak levels of 2.0-3.9 ppm and > or = 4.0 ppm, respectively (P(trend) =.009). Compared with workers exposed to low levels of average exposure intensity of formaldehyde (0.1-0.4 ppm), workers exposed to 0.5-0.9 ppm and > or = 1.0 ppm average intensity had relative risks of 1.15 (95% CI = 0.41 to 3.23) and 2.49 (95% CI = 1.03 to 6.03), respectively (P(trend) =.088). The relative risk for leukemia was not associated with cumulative exposure but was weakly associated with duration of exposure. Relative risks for Hodgkin's disease also increased with formaldehyde exposure. CONCLUSIONS: Exposure to formaldehyde may cause leukemia, particularly myeloid leukemia, in humans. However, results from other investigations are mixed, suggesting caution in drawing definitive conclusions.

Adult↗

Human respiratory tract cancer risks of inhaled formaldehyde: dose-response predictions derived from biologically-motivated computational modeling of a combined rodent and human dataset.

Formaldehyde inhalation at 6 ppm and above causes nasal squamous cell carcinoma (SCC) in F344 rats. The quantitative implications of the rat tumors for human cancer risk are of interest, since epidemiological studies have provided only equivocal evidence that formaldehyde is a human carcinogen. Conolly et al. (Toxicol. Sci. 75, 432-447, 2003) analyzed the rat tumor dose-response assuming that both DNA-reactive and cytotoxic effects of formaldehyde contribute to SCC development. The key elements of their approach were: (1) use of a three-dimensional computer reconstruction of the rat nasal passages and computational fluid dynamics (CFD) modeling to predict regional dosimetry of formaldehyde; (2) association of the flux of formaldehyde into the nasal mucosa, as predicted by the CFD model, with formation of DNA-protein cross-links (DPX) and with cytolethality/regenerative cellular proliferation (CRCP); and (3) use of a two-stage clonal growth model to link DPX and CRCP with tumor formation. With this structure, the prediction of the tumor dose response was extremely sensitive to cell kinetics. The raw dose-response data for CRCP are J-shaped, and use of these data led to a predicted J-shaped dose response for tumors, notwithstanding a concurrent low-dose-linear, directly mutagenic effect of formaldehyde mediated by DPX. In the present work the modeling approach used by Conolly et al. (ibid.) was extended to humans. Regional dosimetry predictions for the entire respiratory tract were obtained by merging a three-dimensional CFD model for the human nose with a one-dimensional typical path model for the lower respiratory tract. In other respects, the human model was structurally identical to the rat model. The predicted human dose response for DPX was obtained by scale-up of a computational model for DPX calibrated against rat and rhesus monkey data. The rat dose response for CRCP was used "as is" for the human model, since no preferable alternative was identified. Three sets of baseline parameter values for the human clonal growth model were obtained through separate calibrations against respiratory tract cancer incidence data for nonsmokers, smokers, and a mixed population of nonsmokers and smokers, respectively. Additional risks of respiratory tract cancer were predicted to be negative up to about one ppm for all three cases when the raw CRCP data from the rat were used. When a hockey-stick-shaped model was fit to the rat CRCP data and used in place of the raw data, positive maximum likelihood estimates (MLE) of additional risk were obtained. These MLE estimates were lower, for some comparisons by as much as 1,000-fold, than MLE estimates from previous cancer dose-response assessments for formaldehyde. Breathing rate variations associated with different physical activity levels did not make large changes in predicted additional risks. In summary, this analysis of the human implications of the rat SCC data indicates that (1) cancer risks associated with inhaled formaldehyde are de minimis (10(-6) or less) at relevant human exposure levels, and (2) protection from the noncancer effects of formaldehyde should be sufficient to protect from its potential carcinogenic effects.

Animals↗

Raised exhaled nitric oxide in healthy children is associated with domestic formaldehyde levels.

Exposure to domestic levels of formaldehyde has been associated with adverse respiratory symptoms in both adults and children. The underlying mechanisms responsible for these findings have not been established. In order to investigate possible inflammatory effects of formaldehyde at levels typically found in the home, we measured exhaled nitric oxide (eNO) in 224 healthy children 6 to 13 yr of age (116 girls) and monitored formaldehyde levels in their homes. Formaldehyde was monitored using a passive sampling technique. Exhaled NO was measured directly into a fast response chemiluminescence nitric oxide analyzer. The children also undertook a lung function (spirometry) test. There was no effect of formaldehyde levels measured in homes on spirometric variables. However, eNO levels were significantly elevated in children living in homes with average formaldehyde levels >/= 50 ppb. Exhaled NO levels (geometric mean) were 15.5 ppb (95% CI: 10.5 to 22.9 ppb) for children from homes with formaldehyde concentrations >/= 50 ppb compared with 8.7 ppb (7.9 to 9.6) for children from homes with formaldehyde concentrations < 50 ppb (p < 0.05). These results suggest that exposure to formaldehyde in homes may invoke a subclinical inflammatory response in the airways of healthy children.

Adolescent↗

In vitro cytotoxicity testing of airborne formaldehyde collected in serum-free culture media.

The purpose of this study was to identify a suitable sampling model for on-site toxicity assessment of soluble air contaminants such as formaldehyde, a well known industrial and indoor air contaminant. The in vitro cytotoxicity of formaldehyde, the selected model for soluble air contaminants, was studied using the MTS (tetrazolium salt) assay in two carcinoma cell lines, A549 epithelial lung and HepG2 hepatocarcinoma, and in skin fibroblasts. The cytotoxic effects of airborne formaldehyde were evaluated using test atmospheres in concentrations below 10 ppm (12.3 mg/m3), generated by a dynamic diffusion method and bubbled (0.3 L/min) through serum-free culture media for one or four hours. Human cells were treated with formaldehyde air samples, and cell viability was determined after four hours incubation. In parallel, the concentration of airborne formaldehyde was monitored, using the 3500 NIOSH method. Cell viability of the HepG2 cells exposed to formaldehyde air samples (8.75 ppm x 4 h) was reduced to less than 50% (31.6 +/- 1.24%). The HepG2 cell lines were found to be more sensitive (IC50 = 103.79 +/- 23.55 mg/L) to formaldehyde than both A549 cell lines (IC50= 198.36 +/- 9.54 mg/L) and skin fibroblasts (IC50 = 196.68 +/- 36.73 mg/L) (P < 0.01). An average of 96.8% was determined for collection efficiency of formaldehyde in serum-free culture media. The results of this study suggest that absorption of soluble air contaminants, such as formaldehyde, in serum-free culture media can be used as a suitable sampling model for on-site toxicity assessments.

Air Pollutants, Occupational↗

Comparison of two formaldehyde administration methods of in ovo-injected eggs.

Formaldehyde administration in the hatchery can be very useful in decreasing microbial numbers. However, its use is controversial because of the adverse effects that can occur to chicks and people. This study was designed to look at alternative methods of application of formaldehyde in the hatchery. In addition, the study compared the effects of these methods of application on in ovo-and non-in ovo-injected eggs. All in ovo-injected eggs were given diluent only with no vaccine or antibiotic added. In hatchers containing both in ovo-injected eggs and non-in ovo-injected eggs, formaldehyde was administered two ways, dose (DOSE) and constant rate infusion (CRI). In the DOSE hatcher, 12 ml of formaldehyde was administered at one time every 12 hr, whereas in the CRI hatcher, the same volume was administered at a rate of 1 ml/hr over a 12-hr period. A control (CONT) hatcher received 12 ml of distilled water at the same time that the DOSE hatcher was given formaldehyde. In the DOSE hatcher, a peak concentration of formaldehyde of 102 ppm was reached. The CRI was maintained at approximately 20 ppm of formaldehyde. At pipping, the aerosol bacterial load in the hatchers receiving formaldehyde (DOSE, 130 colony-forming units [CFU]/m3; CRI, 82.5 CFU/m3) was significantly less than in the CONT hatcher (235 CFU/m3). At hatch, the CRI (337.5 CFU/m3) was not able to control bacterial levels and only the DOSE hatcher (150 CFU/m3) had a significantly lower aerosol bacterial count. The CRI non-in ovo-injected eggs (93.39%) had a significantly higher percentage of hatch of fertile compared with non-in ovo-injected eggs exposed to water (84.27%). In ovo-injected eggs in CONT and DOSE treatment groups contained significantly higher percentages of visual contamination than non-in on-injected eggs in the same hatchers. This difference had numerical significance only in the treatment groups within the CRI hatcher. The chicks were then placed into replicate treatment groups and grown for 14 days. Chicks from the CRI in ovo-injected eggs had a statistically significant improvement in feed conversion ratio (1.24) at 14 days when compared with chicks from CONT non-in ovo-injected eggs (1.29). All formaldehyde-exposed chicks had numerically lower feed conversion ratios compared with the CONT exposed chicks.

Animals↗

Nitrogen utilization and ruminal fermentation in steers fed soybean meal treated with formaldehyde.

Four rumen-fistulated steers averaging 400 kg in body weight were used in a 4 X 4 Latin square arrangement with 18-d periods to investigate the effect of treating soybean meal (SBM) with formaldehyde on nitrogen (N) utilization and ruminal fermentation. Experimental diets, on a dry matter basis, consisted of 42% corn silage, 48.5% cracked corn-mineral mixture and 9.5% SBM treated with 0, .3, .6 or .9% formaldehyde by weight. Dry matter and organic matter digestibilities were not affected by treatment. Formaldehyde treatment of SBM resulted in a linear decrease in N digestibility (P less than .005) and urinary N excretion (P less than .01) and a quadratic increase (P less than .05) in N retention. The depression in apparent N digestibility was small when SBM was treated with .3% formaldehyde. This level of formaldehyde treatment also had little effect on in vitro enzymatic hydrolysis of SBM. Ruminal ammonia-N concentrations were lower (P less than .05) in steers fed formaldehyde-treated SBM. Ruminal pH was lower (P less than .05) at 6 and 8 h postfeeding while volatile fatty acid concentrations were higher (P less than .05) at 8 and 12 h postfeeding for steers fed untreated SBM. Propionic acid (mol/100 mol) decreased linearly (P less than .05) with increasing level of formaldehyde treatment. Urea-N concentrations in plasma were decreased (P less than .001) and plasma-free essential amino acid concentrations were increased (P less than .10) by formaldehyde treatment. Ruminal disappearance of N from polyester bags containing the SBM supplements was greatly reduced (P less than .005) by formaldehyde treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

[Behaviour of DNA-RNase A complex in the presence of formaldehyde].

A formaldehyde-produced fixation of defects caused by a despiralizing action of a protein was studied in the case of DNA-RNAase A complex. The concentration of the defects fixed was measured by kinetic formaldehyde method (KF-method). It was shown that following processes take place in the complex in the presence of formaldehyde: (a) fixation of defects; (b) unwinding of DNA; (c) inactivation of the protein. The rates of all these processes depend on the concentration of formaldehyde, phi. At formaldehyde concentrations above some critical value phic the protein is inactivated before the defects are fixed. At phi less than phic the protein inactivation proceeds more slowly than the fixation of defects; at sufficiently low formaldehyde concentration no inactivation of protein occurs practically during the fixation time (20 min). The number of new defects formed during the time of fixation is linear with the formaldehyde concentration in the region where no inactivation of the protein occurs. Therefore the initial concentration of defects can be determined through an extrapolation to zero concentration of formaldehyde. On the basis of the data obtained a method is proposed for the evaluation of the number of defects in DNA caused by the despiralizing action of proteins. A model is proposed describing the behaviour of the complexes of DNA with despiralizing proteins in the presence of formaldehyde.

DNA↗

[The formaldehyde content in fish in relation to anemia in mink (author's transl)].

The fish-induced anemia in mink is an alimentary disease produced by feeding high amounts of some raw marine fishes. The anemiogenic properties of the fish has been related mainly to its content of the iron binding agent-trimethylaminoxide. The aim of the present investigation was to examine how far formaldehyde could also play a part as an anemiogenic factor. The content of formaldehyde has been analysed in all species of raw, cold stored fish known to be used in mink food and in a few samples of ready made food (Table II). The content of formaldehyde varied within wide limits from 12 to 105 ppm, but none of the measured contents reached the high values obtained by Costly (1970). The mean values of formaldehyde in gutted coalfish, fillet waste of coal fish, cod and haddock prepared for the feeding experiments, were all close to 50 ppm. 175 female mink and 632 mits were tested during the whole of the breeding period from 15.2-30.6, 80 per cent of the diet (page 1) was fish products with and without supplements of formaldehyde. Amounts from 200 to 50 ppm were tried (Table I). The supplement of 200 ppm formaldehyde had an appetite-decreasing and anemiogenic effect, but the supplement of 50 ppm, i.e. a formaldehyde content up to the highest value observed in fillet waste, had no effect on appetite or hemoglobin synthesis neither in females nor in kits. This content of formaldehyde did not counteract the anti-anemiogenic effect of iron glutamate. The fish-induced anemia occurred in mink thus appears unaffected by the quantities of formaldehyde found in fish diets to fur bearing animals. Triox must be regarded as the dominant anemiogenic factor in raw fish diets.

Anemia↗

[Examination related to revised test method for determination of formaldehyde, regulated by the law for the control of household products containing harmful substances].

In Japan, the amount of formaldehyde in textile products was regulated by the low for the control of household products containing harmful substances. Formaldehyde was determined by measuring the optical density of acetylacetone derivative of formaldehyde extracted from textiles. The household products low stated that the increase in the optical density of color development of the extract from the textile products for babies or infants within 24 months after birth should not be more than 0.05. Collaborative study decided the amount of formaldehyde equivalent to the increase in absorbance described above, and the amount was 16 ppm. There are some reports that formaldehyde causes an allergic reaction even at a very low concentration, so continuous regulation for formaldehyde in the textiles was desirable using this level of amount. We developed HPLC method for the determination of formaldehyde in textile products. Formaldehyde was determined by the direct injection of acetylacetone derivative of samples into the system equipped with ODS column and UV-VIS detector (detection wavelength 413 nm) using the mixture of acetonitrile and water as mobile phase. The linearity was obtained between a peak area or height and the concentrations of formaldehyde solution in the range of 0.0625-2 micrograms/ml. The regulation level was sufficiently detected by the present HPLC method. We recommended that the HPLC test was adopted as a reexamination method for the products may violate the regulation as well as a dimedone test.

Chromatography, High Pressure Liquid↗

[Reproductive toxicity of formaldehyde to adult male rats and the functional mechanism concerned].

OBJECTIVE: To assess the reproductive toxicity exerted by formaldehyde to adult male rats and the functional mechanism therein in volved. METHODS: Forty adult male rats were randomLy divided into 4 groups. One group served as control. The other 3 groups as exposure groups were intraperitoneally injected with formaldehyde at the dose of 0.10 mg/kg x d, 1.00 mg/kg x d, 10 mg/kg x d respectively and continuously for 14 days. The weight and morphology of testis, the quality and amount of sperm, and the serum hormone were examined. In addition, the apoptosis rate of testis tissue was examined by TUNEL and the expression of Fas gene in testis tissue by immunohistochemistry. RESULTS: Compared with control, the weight of testis in the high-dose formaldehyde exposure group significantly decreased (P < 0.05); the convoluted tubules became atrophied, the layers of seminiferous epithelium decreased, the arrangement of seminiferous epithelium was in disorder in the medium- and high-dose formaldehyde exposure groups; the sperm count and sperm motility significantly decreased (P < 0.05), the percent of abnormal sperm significantly increased (P < 0.05)in the medium- and high-dose formaldehyde exposure groups; the serum testosterone content mildly decreased and the serum FSH and LH content mildly increased in the formaldehyde exposure groups, but no statistically significant difference was observed. Moreover, in comparison with control, the apoptosis rate and the expression of Fas gene increased in the testicular tissue of rats in the medium- and high-dose formaldehyde exposure groups (P < 0.05). The apoptosis rate was significantly correlated with the expression of Fas gene (r = 0.8832, P < 0. 05). CONCLUSION: Formaldehyde exerts reproductive toxicity to adult male rats, and Fas-mediated apoptosis may be one of the functional mechanisms involved in the reproductive toxicity of formaldehyde.

Animals↗

Detoxification of formaldehyde by acetic acid bacteria.

Formaldehyde resistance of methylotrophic and non-methylotrophic Acetobacter strains was investigated. A facultatively methylotrophic Acetobacter methanolicus (MB58) gets rid of free formaldehyde by assimilating it. Heterotrophically growing cells tolerate 12 mM free formaldehyde. Non-methylotrophic but methanol oxidizing Acetobacter pasteurianus strains possess the same level of formaldehyde resistance. Formaldehyde resistance can be drastically lowered down to 4 mM by blocking the formate dehydrogenase by means of hypophosphite. Acetobacter spp. Martin 1 and LMG 76.10 are not able to oxidize methanol or formaldehyde via formate to CO2 and possess a significantly lower formaldehyde resistance (4 mM). Hence high formaldehyde resistance of the Acetobacter spp. investigated is based above all on a properly operating linear dissimilatory sequence. The dissimilatory RuMP cycle can hardly help detoxify formaldehyde.

Acetobacter↗

[The enzymatic degradation of formaldehyde by isolates of Pseudomonas aeruginosa].

The capacity of 12 Ps. aeruginosa-strains to enzymatically degrade Formaldehyde was tested. These strains, derived from environmental and patient samples, were previously passaged 25 times in increasing formaldehyde-concentrations, in a micromodification of the bacteriostasis test. The formaldehyde-degradation was detected photometrically with the sulfite-pararosaniline-method. Furthermore, in 4 of the 12 strains the activity of a formaldehyde dehydrogenase assumed to be the degrading agent was determined. The tested strains exhibited a markedly differing resistance to formaldehyde, some environmental isolates growing even at concentrations in the range of commonly used disinfectant solutions. The exponential growth phase of the inoculum and the reduction of formaldehyde-content coincided. The strains with the highest formaldehyde-resistance showed a formaldehyde-dehydrogenase activity higher by approximately a factor 100 compared with the rather sensitive ATCC-strain. This dehydrogenase activity, in addition to possible extra- and intracellular penetration barriers, could be a causal factor for an increased formaldehyde-resistance.

Aldehyde Oxidoreductases↗

[Formaldehyde in hair shampoos].

In most hair shampoos commercially available in Western Germany formaldehyde or formaldehyde liberating substances serve as efficient preservatives especially in shampoos of the lower price group. Besides, PHB-ester, mercury containing substances and since recently brome compounds are used for this purpose. We observed a 15 year old patient who developed an allergic contact dermatitis from formaldehyde in a hair shampoo. However, compared to the widespread opportunities of exposure allergic contact dermatitis caused by hair shampoos is not very frequent. For this rarity of formaldehyde dermatitis caused by shampoos the short period of application and the low concentration because of the high dilution and perhaps the low contact dermatitis reactivity of the scalp are responsible. After all only two out of thirtyone thoroughly questioned patients, who had acquired a professional formaldehyde sensitivity elsewhere, reported a contact dermatitis caused by shampoos, which by the way appeared in the orbital region as typical. Probably allergic contact dermatitis from formaldehyde in shampoos will be expected in patients with a formaldehyde sensitivity acquired formerly elsewhere, especially professionally. To those patients formaldehyde free hair shampoos should be recommended. The declaration of formaledehyde in cosmetics, which will be legally obligatory in Germany in 1979, will be valuable for finding out the alternate products free of formaldehyde.

Adolescent↗

Overexpression of ADH1 confers hyper-resistance to formaldehyde in Saccharomyces cerevisiae.

In an attempt to clone genes involved in resistance to formaldehyde we have screened a genomic library based on the episomal plasmid YEp24 for the ability to increase resistance to formaldehyde in a wild-type strain. In addition to SFA, the gene encoding the formaldehyde dehydrogenase Adh5, an enzyme most potent in formaldehyde de-toxification, we isolated a second plasmid that conferred a less pronounced but significant hyper-resistance to formaldehyde. Its passenger DNA contained the gene ADH1, encoding alcohol dehydrogenase 1 (EC 1.1.1.1), which could be shown to be responsible for the observed hyper-resistance phenotype. Construction of an adh1-0 mutant revealed that yeast lacking a functional ADH1 gene is sensitive to formaldehyde. While glutathione is essential for Adh5-mediated formaldehyde de-toxification, Adh1 reduced formaldehyde best in the absence of this thiol compound. Evidence is presented that formaldehyde is a substrate for Adh1 in vivo and in vitro and that its cellular de-toxification employs a reductive step that may yield methanol.

1-Propanol↗

A review and meta-analysis of formaldehyde exposure and pancreatic cancer.

BACKGROUND: Most reviews on the carcinogenicity of formaldehyde have focused on cancers of the respiratory tract. Two recent studies have suggested that exposure to formaldehyde may increase the risk for pancreatic cancer. METHODS: We examine 14 epidemiology studies of workers exposed to formaldehyde where pancreatic cancer rates were reported and use meta-analytic techniques to summarize the findings. We also rank formaldehyde exposures for the industries in these studies. RESULTS: We found a small increase of pancreatic cancer risk in the studies overall (meta Relative Risk [mRR] 1.1, 95%CI 1.0-1.3); however, this increased risk was limited to embalmers (mRR 1.3, 95%CI 1.0-1.6) and pathologists and anatomists (mRR 1.3, 95%CI 1.0-1.7). There was no increased risk among industrial workers (mRR 0.9, 95%CI 0.8-1.1) who on average had the highest formaldehyde exposures. CONCLUSIONS: A small increased risk of pancreatic cancer from formaldehyde exposure cannot be ruled out from the studies examined. However, the null findings among industrial workers and the lack of biological plausibility would argue against formaldehyde as a cause. The increased risk of pancreatic cancer among embalmers, pathologists, and anatomists may be due to a diagnostic bias or to occupational exposures other than formaldehyde in these professions.

Formaldehyde↗

Cancer of the nasal cavity and paranasal sinuses, and formaldehyde exposure.

This case-control study of nasal and paranasal sinus tumors, in males diagnosed between 1978 and 1981 in the Netherlands, was designed to identify environmental risk factors. Special attention was given to assessing any association between nasal cancer and an occupational history of possible formaldehyde exposure while taking into account histologic type of tumor, history of tobacco use, and occupational exposure to wood dust. Of the 116 cases and 259 controls identified, interviews were completed for 91 (78%) of the cases and 195 (75%) of the controls. Adenocarcinoma was strongly associated with a history of high wood dust exposure (RR = 27.0). Two independent assessments of the association between possible formaldehyde exposure and the risk for nasal cancer were carried out (Assessments A and B). By Assessment A the relative risk for nasal cancer associated with possible formaldehyde exposure was 2.5 and by Assessment B it was 1.9. The risk appeared to be most strongly associated with squamous-cell carcinoma and could not be attributed to differences between cases and controls in age, smoking habits, or wood dust exposure. By its retrospective nature, the classification of formaldehyde exposure in this study is not based on known exposures to formaldehyde but on assessment of employment in jobs where formaldehyde exposure is thought possible. Given the limitations of the study, the authors do not consider that it provides conclusive evidence of a carcinogenic effect for formaldehyde, but that it indicates a need for further research--particularly into formaldehyde and squamous carcinoma of the nose.

Adenocarcinoma↗

Sinonasal cancer and occupational exposure to formaldehyde and other substances.

A case-control study of cancer of the nose and paranasal sinuses was conducted in France to determine whether occupational exposure to formaldehyde was associated with an increased risk of sinonasal cancer. Exposures to 14 other substances or groups of substances were also studied (wood dust, leather dust, textile dust, flour dust, sugar dust, coal/coke dust, nickel compounds, chromium compounds, chromium VI, welding fumes, soldering fumes, cutting oils, paints and lacquers, glues and adhesives). Cases (n = 207) and controls (n = 409) were interviewed to obtain detailed information on job history and other potential risk factors for sinonasal cancer. In addition, a questionnaire specially designed for this study was used to help assess exposures to formaldehyde and other substances of interest. The questionnaires were translated into history of occupational exposure by an expert in industrial hygiene, without knowledge of case-control status. Several exposure variables (lifetime average level, duration, cumulative level) were used to describe the risk related to exposure to formaldehyde. Potential confounding factors (occupational and non-occupational) were examined and adjusted for when necessary. No significant association was found between exposure to formaldehyde and squamous-cell carcinomas of the sinonasal cavities. Because of the strong association between exposure to wood dust and nasal adenocarcinoma, it was not possible to assess an independent effect of formaldehyde on this type of cancer. However, among males exposed to medium or high levels of wood dust, the risk of adenocarcinoma associated with formaldehyde was significantly elevated for the highest exposure categories for average level (OR = 5.3, 95% confidence interval = 1.3-22.2), cumulative level (OR = 6.9, 95% CI = 1.7-28.2) and duration of exposure (OR = 6.9, 95% CI = 1.7-27.8). Although a residual confounding effect of wood dust could not be excluded, this study suggests that exposure to both formaldehyde and wood dust may increase the risk of nasal adenocarcinoma, by comparison with the risk due to wood dust alone. This study also indicated an increased risk among males who had been exposed to glues and adhesives, for all histologic types, which was not explained by a confounding effect of paints and lacquers, wood dust or formaldehyde. No other significant association was observed.

Adenocarcinoma↗