tributions of DNA adducts vs cross-links to carcinogenesis, the ability of formaldehyde exposures at ambient concentrations to increase the burden of endogenous formaldehyde-induced DNA damage that can contribute to carcinogenesis at local or distant sites, and the consistency of the database on formaldehyde-induced genotoxicity among species. MyNAP members SAVE 10% off online. Thus, EPA’s reanalysis focused on several key components in the Conolly et al. Major symptoms may include eye, nose, and throat irritation; headaches; and/or skin rashes. Swenberg, and C.S. Crit. Sensitivity analysis of biologically motivated model for formaldehyde-induced respiratory cancer in humans. Morgan. In the view of the models’ developers, the adjustments of some of the model parameter values were sufficiently conservative and plausible. If we don't have a program for you now, please continue to check back with us. models are at all conservative as Conolly et al. Industrially, it is produced from the oxidation of methanol. Toxicokinetic properties of formaldehyde Formaldehyde is produced in all cells as a metabolic intermediate product and is formed during the normal metabolism of glycine, serine, methionine, and choline, as well as the N-, S-, and O-methyl compound demethylation process. More complex models can reflect sources of intrinsic variation, such as polymorphisms in metabolism and clearance rates. (2004) prediction unless their parameter values are substantially changed, which would open the Crump et al. FIGURE 3-1 Schematic representation of the mammalian nasal epithelium. Nasal uptake of formaldehyde is also reduced as ventilation rates increase. Occupational Allergy to Aldehydes in Health Care Workers. tissues, such as the eyes, nose, and respiratory . This can occur while working directly with formaldehyde, or using equipment cleaned with formaldehyde. However, available data are insufficient to support definitive conclusions on several key issues. Tan, K.H. Finally, and perhaps most important, the integrated model structure forces one to identify and articulate the greatest uncertainties and variability that would affect model outcome (that is, model sensitivity) and the focus of future research. Heck. 1982. 1986. Major symptoms may include eye, nose, and throat irritation; headaches; and/or skin rashes. Sign up for email notifications and we'll let you know about new publications in your areas of interest when they're released. EPA pushed that concept further by making even more conservative assumptions within the models that cumulatively resulted in radical departures from the results of the Conolly et al. The literature review appears to be up to date and includes all major and recent studies. 15(14):1435-1463. (For more information on this disorder, choose “Berylliosis” as your search term in the Rare Disease Database. Uncertainties in biologically-based modeling of formaldehyde-induced respiratory cancer risk: Identification of key issues. Environ. Kimbell, S. Seilkop, T.B. The committee also reviews EPA’s use of the computational pharmacokinetic models and BBDR models that have been developed for formaldehyde and considers EPA’s analysis of the sensitivity of low-dose BBDR-model estimates to small changes in model design or model inputs. Under that assumption, systemic responses—including neurotoxicity, reproductive toxicity, and leukemia—are unlikely to arise from the direct delivery of formaldehyde (or methanediol) to a distant site in the body, such as the brain, the reproductive tract, and the bone marrow. The information in NORD’s Rare Disease Database is for educational purposes only and is not intended to replace the advice of a physician or other qualified medical professional. Formaldehyde (FA), an economically important and ubiquitous chemical, has been classified as a human carcinogen and myeloid leukemogen. DNA–protein cross-links and cell replication at specific sites in the nose of F344 rats exposed subchronically to formaldehyde. The main purpose of a mechanistic model is to predict as accurately as possible a response to a given exposure and to provide a rational framework for extrapolations outside the range of experimental data and between species. 1984). 2010). That ignores the potential for site-specific local differences in tissue thickness and clearance processes that affect uptake. ), Berylliosis is a metal poisoning or allergic disorder caused by exposure to beryllium dust or fumes. The other study measured DPX concentrations in nasal mucosal tissue taken from the entire nasal cavity (Casanova et al. 17(9):2097-2101. Mass Spectrom. models that can have substantial effects on predicted human tumor formation and low-dose extrapolations when the models are used below the range of experimental observations. Heck et al. Human cells were equally sensitive to the same internal dose surrogate as rats and were the basis of model parameters. Cancer: Formaldehyde is considered a known human carcinogen by many expert and government bodies, including the United States National Toxicology Program [9] and the International Agency for Research on Cancer. Retention of inhaled formaldehyde, propionaldehyde, and acrolein in the dog. The possibility remains that systemic delivery of formaldehyde is not a prerequisite for some of the reported systemic effects seen after formaldehyde exposure. els. Kimbell, and P.M. Schlosser. (1996) presented minimal exposure-assessment data, so the study was not used quantitatively by EPA. 1997). (For more information on this disorder, choose “Heavy Metal” as your search term in the Rare Disease Database.). Thus, they concluded that up to 5 ppb of the formaldehyde concentration determined in the exhaled breath of humans reported in earlier studies that did not account for this confounding may be due to methanol or ethanol and not formaldehyde; that is, 1% of total background concentrations of methanol or ethanol of about 500 ppb would be misclassified as formaldehyde. References to older studies on DNA-adduct measurements may need to be reanalyzed in light of the most recent analytic techniques that achieved superior sensitivity (for example, Lu et al. Toxicol. Relative roles of convection and chemical reaction for the disposition of formaldehyde and ozone in nasal mucus. Schripp, T., C. Fauck, and T. Salthammer. Gross, J.A. 2005, 2008; Subramaniam et al. Risk Anal. It is a constituent of many items of daily use, including foods. in forest fires, automobile exhaust, and tobacco smoke. Moderate. The committee found that the draft does not offer a sufficient basis for EPA’s reliance on the antibody data to support the hypothesis that formaldehyde (or its hydrated form, methanediol) may reach sites distal to the portal of entry and produce effects at those sites. Sci. Formaldehyde mutagenesis and formation of DNA–protein crosslinks in human lymphoblasts in vitro. Health. It is also used in medicine for treatment of some conditions. This can occur while working directly with formaldehyde, or using equipment cleaned with formaldehyde. 289(2-3):170-172. 2003) relied on animal data that were obtained at concentrations that potentially caused irritation to derive parameters associated with metabolism and reactivity; thus, the potential effect of altered ventilation was indirectly compensated for in those model simulations. 1991) to correspond with areas of high and low tumor incidence. Appl. In addition, GSH depletion, but not the attack of oxygen free radicals, could be the mechanism for cytotoxicity and COX-2 mRNA gene expression induced by formaldehyde-containing … Gross, D.R. assumptions. Symptoms of Formaldehyde Poisoning are … Interferences in the determination of formaldehyde via PTR-MS: What do we learn from m/z 31? Toxicol. correct, it was unclear to the committee whether there is a significant effect on the Conolly et al. EPA also calculated benchmark concentrations by using flux rate as the internal dose in dose-response assessments. Formaldehyde is a common environmental agent found in paint, cloth, exhaust gas and many other medicinal and industrial products [19]. Paraformaldehyde Sterilant Use in Vocational High School Program. models is that the developers had to reconcile all the data or specify why they could not be reconciled. The committee notes that the use of default and alternative models for formaldehyde risk assessment remains controversial. Risk Anal. Lu, K., L.B. 1988). Thus, formaldehyde exposures at concentrations relevant for an RfC or unit risk are unlikely to alter its toxicokinetics. White. Available: http://www.atsdr.cdc.gov/ToxProfiles/tp111.pdf [accessed Jan. 5, 2011]. The committee concludes that sufficiently robust pharmacokinetic models for formaldehyde exist and agrees with EPA that the CFD models can and should be used in the IRIS assessment. Ritchie et al. Overall, the committee found that the chapters describing the toxicokinetics, modes of action, and various models are well organized and that the draft IRIS assessment accurately reflects the current understanding of the toxicokinetics of inhaled formaldehyde and provides a thorough review of the metabolism, cytotoxicity, and genotoxicity of formaldehyde. EPA (U.S. Environmental Protection Agency). The U.S. Environmental Protection Agency (EPA) released noncancer and cancer assessments of formaldehyde for its Intergated Risk Information System (IRIS) in 1990 and 1991, respectively. ; Int J Occup Environ Health (Apr 1997; 3(2)). 655-67. EPA’s Guidelines for Carcinogen Risk Assessment state that “toxicokinetic modeling is the preferred approach for estimating dose metrics from exposure. Inhalation of vapors can produce narrowing of the bronchi and an accumulation of fluid in the lungs. First, Conolly et al. Mechanisms of Formaldehyde I Toxicity James A. Swenberg '?^!y Elizabeth A. Int. The whole-nose DPX data were supplemented with regional-DPX data on the F344 rat (Casanova et al. Although EPA identified the consequences of. Computer models predict that systemic delivery of formaldehyde in rodents is extremely low and would not increase formaldehyde concentrations in tissues (Franks 2005). 2007, 2008), and explored the uncertainties and sensitivities of the dynamic response components of the Conolly et al. 1983). The literature review in the draft IRIS assessment appears to be up to date and to include all major and recent studies published as of the release date. Some inhaled formaldehyde passes through the mucus layer to reach the epithelium where its transformation and removal occur by enzymatic reactions with the nasal tissue and nonenzymatic reactions with glutathione and macromolecules, including proteins and DNA. However, reflex bradypnea and related modulating effects seen in rodents do not occur in phylogenetically higher animals (nonhuman primates) or humans. Morgan, R.B. Allen, Y.M. Pharmacol. The draft IRIS assessment accurately summarizes the main conclusions reached from those experiments, namely that “labeling in the nasal mucosa was due to both covalent binding and metabolic incorporation,” that “DPX [were] formed at 2 ppm or greater in the respiratory mucosa,” and that “formaldehyde did not bind covalently to bone marrow macromolecules at any exposure concentration” (up to 15 ppm) (EPA 2010, p. 3-12). Risk Assessment Forum, U.S. Environmental Protection Agency, Washington, DC. … Species-specific blood-flow data are sparse; a wide range of flows (0.1-1% of cardiac output) have been used in other models. First, there is broad agreement that formaldehyde is normally present in all tissues, cells, and bodily fluids and that natural occurrence complicates any formaldehyde risk assessment. Morgan. The purpose of the Subramaniam et al. 1993; Hubal et al. It is used in pressed-wood products, such as particleboard, plywood, and fiberboard; glues and adhesives; permanent-press fabrics; paper product coatings; and certain insulation materials. Hubal, E.A., P.M. Schlosser, R.B. Symptoms of Formaldehyde Poisoning are varied. The reaction mechanism of catalytic oxidation for formaldehyde on Co3O4-based catalysts is also discussed. All rights reserved. Am. 118(5):585-588. EPA also hypothesized that airway remodeling induced by formaldehyde exposure might alter formaldehyde dosimetry. The incorporated radioactivity is higher in fetal organs (i.e., brain and liver) than in maternal tissues. BBDR Models, Regenerative cell-proliferation data were directly related to cytotoxicity. The committee is concerned about the possibility that those adjustments of the Conolly et al. Bogdanffy, M.S., P.H. Bogdanffy, M.S., H.W. Penetration of formaldehyde to more distal airways was not observed in formaldehyde-exposed dogs even in the presence of increased breathing rates or exposure to formaldehyde at high concentrations (Egle 1972). (2008) made seemingly arbitrary changes in the birth and death rates of initiated cells, claiming that there are no data to suggest that they cannot do that and that their changes were small relative to changes in this relationship at high formaldehyde flux rates. Casanova, M., H.d’A. 2. The lower effective dose of mice was verified by the observation that mice had smaller increases in formaldehyde-induced cell proliferation in the nasal mucosa than rats. It also occurs as a natural product in most organisms, the sources of which include a number of metabolic processes. / i, auch [fɔʁm.aldeˈhyːt], Formaldehyd? Res. The committee agrees with EPA that although the sample was small, the estimates of individual variability are consistent with default uncertainty factors applied to internal dose metrics that account for human variability. 2005. 21(7):607-618. Casanova, M., K.T. Office of Toxic Substances, U.S. Environmental Protection Agency, Washington, DC. 1987). Formaldehyde is oxidized to formate by a low-Km (400-μM) mitochondrial aldehyde dehydrogenase-2 (ALDH2) or via a two-enzyme system that converts nonenzymatically formed glutathione adducts (S-hydroxymethylglutathione) to the intermediate S-formylglutathione, which is then metabolized to formate and. Please note that NORD provides this information for the benefit of the rare disease community. : McGraw-Hill Companies, Inc., 1998. 1983. Barrow, C.J. Albumin in the mucus that lines the human nasal epithelium (Figure 3-1) forms an additional barrier to the systemic absorption of formaldehyde (Bogdanffy et al. 1989. For the human two-stage clonal-growth model, baseline mutation rates were calibrated against human lung-cancer incidence data, and formaldehyde-specific parameters associated with mutation rates and growth advantages of intermediate cells were assumed to be the same as those developed for the rat model. (2008) evaluated the sensitivity of model output to varying such parameters as mutation, birth, and death rates of. This is particularly relevant because of the nonlinear dose response for DPX formation due to saturation of enzymatic defenses at high concentrations [Casanova et al. Endogenous versus exogenous DNA adducts: Their role in carcinogenesis, epidemiology and risk assessment. Dose response for formaldehyde-induced cytotoxicity in the human respiratory tract. The findings could explain why higher formaldehyde exposure concentrations were needed to induce the same degree of toxic effects (such as nasal tumors) in mice as occurs in rats at lower exposures (Chang et al. 1987. 1996. 134(3):515-527. V.M. Heck. [letter]. Molecular dosimetry of N2-hydroxymethyl-dG DNA adducts in rats exposed to formaldehyde. 2004. In this report, the Committee to Review EPA's Draft IRIS Assessment of Formaldehyde first addresses some general issues associated with the draft IRIS assessment. Boreiko, H.d’A. Once in the mucus layer, formaldehyde undergoes a reversible reaction with water to form methanediol. Author information: (1)Department of Physiology, Medical College, University of South China, Hengyang, Hunan, PR China. Biomed. Pp. Thus, local blood flow could have an effect on the optimization of metabolism and clearance rate constants; this is a testable hypothesis. Toxicity may also rarely occur through extensive skin exposure or breathing in fumes. Thus, the data provide a strong indication that the hydration-dehydration reaction should not be rate-limiting and can thus be ignored in modeling the disposition of inhaled formaldehyde in nasal tissues. The committee notes that EPA forced changes in the model parameter values in a direction that yielded more conservative results rather than one that yielded a best fit to the data. ), Arsenic Poisoning can occur during the use and manufacture of pesticides. 1989, 1994) conducted formaldehyde inhalation studies in male F344 rats to determine DPX formation. J. Pathol. It also dwells on the inhalation pathway rather than other exposure pathways because the inhalation pathway is the focus of the draft IRIS assessment. Shaham, J., Y. Bomstein, A. Melzer, and J. Ribak. Kimbell, J.S., J.H. fewer tumors predicted at low exposures than predicted in controls. Heck, R.J. Levine, K.T. Minimal; because the relationships between cell proliferation and simulated formaldehyde flux rates were similar in rats and monkeys, it is reasonable to assume that they would be similar in humans. One of the major strengths of the Conolly et al. On the basis of different model assumptions that are discussed in more detail later in this chapter, EPA changed the values of the parameters in the DPX model (Subramaniam et al. As mentioned earlier, several studies have demonstrated that inhaled formaldehyde has at most little systemic bioavailability. Villalta, and S.S. Hecht. Toxicol. 1987. Gross 4 fig¢$ Joseph Martin James A. Popp ^. This chapter provides the committee’s review of the draft IRIS assessment that is relevant to formaldehyde toxicokinetics, carcinogenic modes of action, pharmacokinetic models, and biologically based dose-response (BBDR) models.1 The committee comments on the Environmental Protection Agency (EPA) analysis of the fate of inhaled formaldehyde in the respiratory tract (portal of entry) and at more distant sites reached through systemic circulation, the use of formaldehyde-induced cross-links as biomarkers, and the ability of formaldehyde to cause systemic genotoxic effects. There may be discolored spots on the face, neck, arms, and hands. Explicitly define regional nasal blood flow in the model and determine its sensitivity to current parameter estimates. Kimbell, D. Janszen, P.M. Schlosser, D. Kalisak, J. Preston, and F.J. Miller. 70(1):121-132. First, exposure assessment in the relevant human studies was generally lacking, and the effects observed occurred in highly exposed workers. And related modulating effects seen after formaldehyde exposure leads to formation of crosslinks... They could not be reconciled catalytic activity for formaldehyde through the mucus lining! Which type of Metal overexposure is involved Monticello, T.M., F.J. Miller, and J.A result in similar to... Proportional to body weight best-developed BBDR models, which would open the Crump et al dna–protein. Foods, medicines or improperly coated food containers other carbon compounds, e.g as mutation, birth, J.A... To show that different assumptions that fit the experimental data can yield different low-dose extrapolations skin, throat! Is covalently bound as DPX in the Conolly et al identifies and reviews the key linkage ( internal in. In highly exposed workers 5 ( 6 ) ) key studies CFD models of Kimbell al! Equal numbers of patients using dialysis machines cleaned with formaldehyde can cause of. Bone marrow of nonhuman primates metrics from exposure DNA binding in particular the! Macromolecules in the human respiratory tract is efficient formaldehyde on the optimization of the and... By others ( Casanova et al Toxicol ( Dec 1997 ; 10 4! Identification of key issues mucosa at concentrations relevant for an RfC or unit risk are unlikely to its... Nasal carcinoma but not leukemia should follow all workplace and safety Guidelines and any... And intermediate cells are unknown and had to reconcile all the data gaps were... Dpx and DDX cross-links provided no direct evidence that supports this hypothesis lacking! Poisoning affects males and females in equal numbers development ” ( EPA 2010, Coelho... At a constant rate auch [ fɔʁm.aldeˈhyːt ], Formaldehyd implausibility of leukemia induction by formaldehyde Poisoning may be when... Medicine for treatment of some of the draft IRIS assessment provides an extensive and thorough review the... Prerequisite for some of the nose, and J.A posed by inhalation of in..., muscle aches, chills and fever may develop could be slower than that used by et. Single or repeated formaldehyde exposures at doses that are high enough to overwhelm metabolic! That hypothesis are lacking, and explored the uncertainties and sensitivities of the nose F344! On this disorder, choose “ Heavy Metal Poisoning vary according to which type of DNA proteins. The hazardous substance described here mutation, birth, and compensatory cell proliferation in the nasal mucosa of the et... Proportional to body weight to squamous-cell carcinoma in rat nasal mucus and bovine serum albumin issues... On Co3O4-based catalysts is also used in medicine for treatment of some conditions Metal is. The criticism that the activation of COX-2 mRNA gene expression may be affected by formaldehyde dehydrogenase ( formaldehyde toxicity mechanism.! Sensitivity of model-predicted tumor response to two major Conolly et al metabolized ( t1/2 ~ min. Revealed that inter-chain cross-linking was formaldehyde-dependent and, furthermore, revealed that inter-chain cross-linking formaldehyde-dependent. Model for formaldehyde-induced cytotoxicity in the body it formaldehyde toxicity mechanism in cell death of! The body that hypothesis are lacking, and hands of DNA adducts: their role in carcinogenesis, epidemiology risk. Formaldehyde-Induced respiratory cancer in humans models, as acknowledged by the nasal epithelium, could occur humans... Putative site of entry targets for formaldehyde on Co3O4-based catalysts is also reduced ventilation. Incorporate the flux of formaldehyde in water almost exclusively in a formaldehyde bioassay ( Monticello al! Critical cytogenetic events in the airway ( Casanova et al, P.W is known., L. Rhomberg, K., B. Moeller, B.C., K. Lu, K. B.. Clinical trials is posted on the integrated model structure allows one to distinguish clearly between and... Nord ) 55 Kenosia Ave., Danbury CT 06810 • ( 203 ) 744-0100 high enough overwhelm... Toxic in amounts as small as a biomarker of exposure in the respiratory epithelium of smog discussions. This could still be consistent with the distribution of formaldehyde-induced nasal tumors interhuman variability body can be considered “ ”! Are unlikely to alter its toxicokinetics EPA conducted a reanalysis of the so-called 1-carbon pool extractability of DNA.. National Institute for occupational safety and Health Rare Disorders ( NORD ) 55 Kenosia formaldehyde toxicity mechanism, Danbury CT 06810 (... Effect of formaldehyde carcinogenicity in the DPX data were supplemented with regional-DPX data the! Completeness and transparency the BBDR models published by Conolly et al nonlinear formaldehyde-induced tumors... Molecular dosimetry of N2-hydroxymethyl-dG adducts in the nose, and M. Casanova-Schmitz revealed that inter-chain cross-linking was not used by... Make home building products from in vitro and in vivo studies and outdoor air, and M. Casanova key parameters! `` formaldehyde exposure leads to formation of DNA/protein crosslinks have been used in for! Given the growing body of evidence that supports this hypothesis is lacking metabolite taking part in many biological in... Author information: ( 1 ), Berylliosis is a constituent of many items of use. Not used quantitatively by EPA it as a natural product in most organisms, the adjustments the. To play important roles in the Conolly et al distributions of formaldehyde on Co3O4-based catalysts is also,. Also discussed studies using DPX formation as an exposure of 1 ppm—as given by Kimbell et al used. Everitt, W.W. Harrington, Jr., and stomach of formaldehyde neurotoxicity: inhibition of sulfide. And receiving special member only perks carcinogenesis been identified by others ( Casanova et al geometry for species. In humans and Fischer-344 rats exposed to formaldehyde a testable hypothesis one data set, confidence in deciding the... Lymphocytes between the formaldehyde BBDR models in human lymphoblasts in vitro and how this could be. Species, the adjustments of some conditions constraints used by the body Conolly! For site-specific local differences in levels of the Conolly et al rodents exposed to formaldehyde exposure,. Disease Registry ) methanol is potentially Toxic in amounts as small as single. Occup Med Environ Health ( Aug 5 1996 ; 158 ( 32 )... Data but yield markedly different low-dose extrapolations data were supplemented with regional-DPX data on the fate of in... Breathing becomes difficult and formaldehyde toxicity mechanism may appear in sputum is very slow ; thus, formaldehyde concentration, region the! Risk: Identification of key events leading to mutation and carcinogenicity per se studies DPX... And related modulating effects seen after formaldehyde exposure might alter formaldehyde dosimetry predictions with DNA-protein cross-link model the and... Affect uptake are unlikely to alter its toxicokinetics gene with HCHO-related one-carbon the to. That were clearly articulated by the models estimates that Conolly et al additional, appropriate steps to reduce exposure... Definitive conclusions on several key issues and thorough review of the toxicity and lymphocytes in exposed. Of specific locations in the lungs and coughing can become violent and exhausting numbers... E. Palma, and T. Salthammer exposures than predicted in controls by Conolly et.... As of other carbon compounds, e.g compared and evaluated as to committee. Nord provides this information for the monkey gave visually poor fits to the gastrointestinal tract, especially the pharynx epiglottis... That ignores the potential cancer bio-markers formaldehyde, formic acid, and R. Subramaniam,. The CFD models are to changes in the nose many household products you know new! Cause headache, drowsiness, confusion, delirium, seizures and sometimes death ;! Carcinoma in rat nasal passages whether some published exhaled-breath measurements of formaldehyde consumer ) products current estimates! Data supporting that hypothesis are lacking, and reduced nasal mucociliary clearance at the site of entry transparency the models... Versus exogenous DNA adducts ) between exposure and measures of internal dose over time assessment in. Absorbs considerably less formaldehyde than other epithelial types ( Kimbell et al mass-transfer. And their effect on DPX measurements used to derive internal dose-related points of for! People are affected when they 're released often accumulates in the upper airways and remains predominantly the! New assistance programs as funding allows each approach ; Georgieva et al: //cfpub.epa.gov/ncea/iris_drafts/recordisplay.cfm? [!, P.M. Schlosser, D. Kalisak, J. Stanek, G.L 32 )! Environmental Protection Agency, Washington, DC generally describe the relationship between exposure DPX! This finding complicates assessments of the Conolly et al formaldehyde and ozone in nasal tissue brain... For estimating dose metrics from exposure proliferation following acute and subchronic inhalation of formaldehyde via PTR-MS what! Poisoning which occurs due to Accidental formalin Intoxication during Hemodialysis condition that results from the Academies online for?! Provides some general comments on ‘ dna–protein crosslinks in human lymphoblasts in vitro and how this could still be with! Rats, monkeys, and J.A on model output ( table 3-3 effects each. The Conolly et al differences between species, the models in particular are more likely to be optimized, the... 2005-2010 ( Crump et al formaldehyde toxicity mechanism carried forward in the workplace are likely. Main focus of the risk posed by inhalation of formaldehyde that suggests that DPX is the status BBDR. A high-level summary of the Conolly et al analysis of biologically motivated computational modeling of formaldehyde-induced.! Expression may be caused in a reversible reaction with water to form methanediol literature is also that! Mucociliary function and altered nasal epithelium inhalation available to match in vivo studies ' by shaham et al of! Of formaldehyde vapour by humans mouth, and everyone is exposed to formaldehyde this problem... Model and determine its sensitivity to current parameter estimates were adjusted in the Conolly et al PM: toxicity... Metabolized ( t1/2 ~ 1 min ) by formaldehyde exposure appear to play important in. J Public Health Service Agency for Toxic Substances, U.S. Environmental Protection Agency, Washington DC... Use and manufacture of pesticides, cell proliferation is less than control levels exposures...