Formaldehyde Toxicity—New Understanding

Heck, Henry d’A.; Casanova, Mercedes; Starr, Thomas B.

doi:10.3109/10408449009029329

Cited by 253 publications

(128 citation statements)

References 164 publications

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“…This raises the important question of whether another type of DNA damage is generated through DPC hydrolysis. Previous in vitro studies demonstrated DPCs were induced by formaldehyde with formation of N-CH 2 -N and N-CH 2 -S linkages between DNA and protein (Heck et al, 1990). To study the chemical identity of formaldehyde-induced DPCs, we investigated the in vitro crosslinking reaction between nucleosides, nucleotides, and amino acids and peptides in the presence of formaldehyde (Lu et al, 2010b).…”

Section: Discussionmentioning

confidence: 99%

Formation, Accumulation, and Hydrolysis of Endogenous and Exogenous Formaldehyde-Induced DNA Damage

Yu¹,

Lai²,

Hartwell³

et al. 2015

Toxicol. Sci.

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Formaldehyde is not only a widely used chemical with well-known carcinogenicity but is also a normal metabolite of living cells. It thus poses unique challenges for understanding risks associated with exposure. N 2-hydroxymethyl-dG (N 2 -HOMedG) is the main formaldehyde-induced DNA mono-adduct, which together with DNA-protein crosslinks (DPCs) and toxicityinduced cell proliferation, play important roles in a mutagenic mode of action for cancer. In this study, N 2 -HOMe-dG was shown to be an excellent biomarker for direct adduction of formaldehyde to DNA and the hydrolysis of DPCs. The use of inhaled [ 13 CD 2 ]-formaldehyde exposures of rats and primates coupled with ultrasensitive nano ultra performance liquid chromatography-tandem mass spectrometry permitted accurate determinations of endogenous and exogenous formaldehyde DNA damage. The results show that inhaled formaldehyde only reached rat and monkey noses, but not tissues distant to the site of initial contact. The amounts of exogenous adducts were remarkably lower than those of endogenous adducts in exposed nasal epithelium. Moreover, exogenous adducts accumulated in rat nasal epithelium over the 28-days exposure to reach steady-state concentrations, followed by elimination with a half-life (t 1/2 ) of 7.1 days. Additionally, we examined artifact formation during DNA preparation to ensure the accuracy of nonlabeled N 2 -HOMe-dG measurements. These novel findings provide critical new data for understanding major issues identified by the National Research Council Review of the 2010 Environmental Protection Agency's Draft Integrated Risk Information System Formaldehyde Risk Assessment. They support a data-driven need for reflection on whether risks have been overestimated for inhaled formaldehyde, whereas underappreciating endogenous formaldehyde as the primary source of exposure that results in bone marrow toxicity and leukemia in susceptible humans and rodents deficient in DNA repair.

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Section: Discussionmentioning

confidence: 99%

Formation, Accumulation, and Hydrolysis of Endogenous and Exogenous Formaldehyde-Induced DNA Damage

Yu¹,

Lai²,

Hartwell³

et al. 2015

Toxicol. Sci.

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“…FA enters the mono-carbon (C1) pool of cellular metabolism via binding to tetrahydrofolic acid; as such, it can participate in the structure of macromolecules, such as nucleic acids. [7][8][9][10][11][12][13] FA exists at varying levels in cells, but it cannot be stored in the body. It is excreted either in the feces or urine as formic acid or via the respiratory tract as carbon dioxide.…”

Section: Biochemical Features Of Formaldehydementioning

confidence: 99%

Toxic effects of formaldehyde on the urinary system

İnci

Zararsız

Davarci

et al. 2013

Turkish Journal of Urology

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Formaldehyde is a chemical substance with a pungent odor that is highly soluble in water and occurs naturally in organisms. Formaldehyde, when taken into organisms, is metabolized into formic acid in the liver and erythrocytes and is then excreted, either with the urine and feces or via the respiratory system. Formaldehyde is widely used in the industrial and medical fields, and employees in these sectors are frequently exposed to it. Anatomists and medical students are affected by formaldehyde gas during dissection lessons. Because full protection from formaldehyde is impossible for employees in industrial plants using this chemical and for workers in laboratory conditions, several measures can be implemented to prevent and/or reduce the toxic effects of formaldehyde. In this review, we aimed to identify the toxic effects of formaldehyde on the urinary system.

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“…Parallel histopathology studies demonstrated that formildehyde-induced nasal lesions were highly site specific n both rats (90, 97) and rhesus monkeys (87 (53). To date, the application of DPX to human risk assessment has used these cross-links solely as a molecular dosimeter (55).…”

Section: Introductionmentioning

confidence: 99%

“…These and related studies have been reviewed in detail (53). The absence of DPX from the olfactory mucosa jraws attention to the importance of the site specificitỹ f formaldehyde-induced DPX.…”

Section: Introductionmentioning

confidence: 99%

“…As a direct consequence of this finding, the Consumer Product Safety Commission (CPSC) issued a &dquo;Ban of Urea-Formaldehyde Foam Insulation&dquo; on April 2,1982 (32). This decision drew increased attention to the nose as a target organ and to the problems associated with extrapolation from rodent nasal responses to human disease risk for formaldehyde and other chemicals (28,42,53,57,119,122). It was recently stated by DeSesso (35), on the basis of a literature review, that the rat nose is a poor model for the study of toxic and carcinogenic effects of inhaled materials.…”

Section: Introductionmentioning

confidence: 99%

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Review Article: A Brief Review of Formaldehyde Carcinogenesis in Relation to Rat Nasal Pathology and Human Health Risk Assessment

Morgan

1997

Toxicol Pathol

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The 1980 report that inhaled formaldehyde induced nasal squamous cell carcinomas in rats had a significant societal impact and resulted in extensive research in the fields of rodent nasal pathology and human cancer risk assessment. This article presents an overview of the evolution of these events. It is concluded that the nasal passages of humans and rats are fundamentally identical biological target organs. Nevertheless, in the case of human health risk assessment, minor differences between these species may be critically important. Special attention should be paid to interspecies differences in nasal dosimetry and local metabolism; thus, chemical toxicity data derived from rats require careful interpretation when used for human risk assessments. In the case of formaldehyde, it is recommended that lowconcentration (≤2 ppm airborne exposure) extrapolation, where no tissue damage is observed, be uncoupled from the responses at high concentrations (≥6 ppm), where epithelial degeneration, regenerative cell replication, and inflammation appear to be essential driving forces in formaldehyde carcinogenesis. The presence of treatment-related nasal lesions in rats following exposure to chemicals should always be treated as an indication of a potential human health risk, whether exposure is by the inhalation, oral, or dermal route.

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Formaldehyde Toxicity—New Understanding

Cited by 253 publications

References 164 publications

Formation, Accumulation, and Hydrolysis of Endogenous and Exogenous Formaldehyde-Induced DNA Damage

Formation, Accumulation, and Hydrolysis of Endogenous and Exogenous Formaldehyde-Induced DNA Damage

Toxic effects of formaldehyde on the urinary system

Review Article: A Brief Review of Formaldehyde Carcinogenesis in Relation to Rat Nasal Pathology and Human Health Risk Assessment

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