That ignores the potential for site-specific local differences in tissue thickness and clearance processes that affect uptake. Conolly, R.B., J.S. 1989. 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). Fox, C.J. Environ. Formaldehyde crossing the basement membrane can react further with macromolecules in the submucosal layer or reach the systemic circulation. Moreover, the draft IRIS assessment does not evaluate the antibody work as critically as the direct chemical-analysis approaches. Pp. Regardless, the committee recommends that for completeness and transparency the BBDR models published by Conolly et al. Although the curing of urea formaldehyde can take place at room temperature using the addition of an acid catalyst (such as citric or formic acid) to drive the reaction, the manufacture of panel products is generally driven by speed or production and therefore the reactions take place in the presence of heat. Zhiying Ji, Cliona M. McHale, Jessica Bersonda, Judy Tung, Martyn T. Smith, Luoping Zhang, Induction of … The local tissue concentration is determined from CFD-derived formaldehyde flux rates, the thickness of the epithelium, and saturable metabolism and first-order clearance from the tissue. J. Occup. Strict control and protective measures must be employed in the workplace to minimize formaldehyde exposure to the lowest possible limits. Abbreviations: DPX, DNA-protein crosslinks; BBDR, biologically based dose-response; CFD, computational fluid dynamics; EPA, Environmental Protection Agency; and MVK, Moolgavkar-Venzon-Knudson. Acute Toxicity of Formaldehyde The acute effects of formaldehyde exposure appear to be largely a result of its irritant properties. The authors argued that—inasmuch as there are no data that define mutation, birth, and death rates of initiated cells, let alone data that identify what an initiated cell is—the onus is on others to demonstrate that the small changes that they made in the Conolly et al. EPA also hypothesized that airway remodeling induced by formaldehyde exposure might alter formaldehyde dosimetry. Toxicol. Craft, T.R., E. Bermudez, and T.R. 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. Moss, and H.d’A. Mater. Binding of formaldehyde to human and rat nasal mucus and bovine serum albumin. Two statistical models were evaluated that relate time- and site-averaged cell proliferation data to formaldehyde exposure. Am. The committee, however, recommends that the CFD models be used to extrapolate to low concentrations, that the results be included in the overall evaluation, and that EPA explain clearly its use of the CFD modeling approaches. Subramaniam, and P.D. Biomed. The endogenous formaldehyde level is multidimensional (ATSDR 1999). Metaplasia of the anterior nasal epithelium to a squamous epithelial phenotype occurs in rats exposed repeatedly to formaldehyde at 3 ppm or higher (Kimbell et al. 21(7):607-618. The draft IRIS assessment raises the criticism that the nasal CFD models are based on a single geometry for each species. initiated cells and concluded that small changes in these parameters can result in similar fits to experimental data but yield markedly different low-dose extrapolations. Although the committee agrees with much of the narrative, several issues need to be addressed in the revision of the draft assessment. Formaldehyde is an organic compound with numerous industrial uses. (1996). Spanel, P., and D. Smith. Risk assessment of formaldehyde. 1997. 1993. Despite the concerns raised, EPA used the CFD models to derive human-equivalent concentrations (HECs) on the basis of formaldehyde flux rates. models may not be scientifically defensible. EPA (U.S. Environmental Protection Agency). Choices of model structure and associated parameters used to describe DPX-formation data and cell-proliferation data collected in rats and monkeys as a function of time and exposure (that is, linear vs J-shaped vs hockey-stick-shaped dose-response curves). 1). In particular, adjustments of parameter values associated with mutation, birth, and death rates of initiated cells used in EPA’s analysis of alternative models that yielded the most extreme deviations from the Conolly et al. Covalent binding of inhaled formaldehyde to DNA in the nasal mucosa of Fischer 344 rats: Analysis of formaldehyde and DNA by high-performance liquid chromatography and provisional pharmacokinetic interpretation. Potential mechanisms underlying formaldehyde-induced reproductive and developmental toxicities, including chromosome and DNA damage (genotoxicity), oxidative stress, altered level and/or function of enzymes, hormones and proteins, apoptosis, toxicogenomic and epigenomic effects (such as DNA methylation), were identified. 25(2):119-124. EPA’s analysis (EPA 2010) evaluated the following: Choice of background nasal-tumor incidence data in rats and total respiratory-tumor incidences in humans, which were used to define basal mutation rates for normal and intermediate cells. Environ. 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