US EPA

1311654 

Journal Article 

Specific identification of formaldehyde-mediated mutagenicity using the mouse lymphoma L5178Y TK +/- assay supplemented with formaldehyde dehydrogenase 

Blackburn, GR; Dooley, JFI; Schreiner, CA; Mackerer, C 

1991 

Yes 

In Vitro Toxicology
ISSN: 0888-319X 

4 

2 

121-132 

English 

https://search.proquest.com/docview/48402070?accountid=171501
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Formaldehyde (HCHO) is used in the synthesis of a wide variety of industrial chemicals. In some cases, the HCHO is stoichiometrically consumed during the synthesis, and is found only at trace levels in the finished product. In other cases, the reaction is reversible, and release of active formaldehyde can occur; (e.g., certain industrial biocides exert their bacteriocidal effect by this mechanism). Products which contain or release HCHO are mutagenic in bacterial and mammalian cell mutagenicity assays. We have developed a modification to the mouse lymphoma L5178Y TK+/-assay that permits determination of whether a suspect material is inherently mutagenic or is active solely because it contains HCHO in free or latent form. The modification involves addition of the enzyme formaldehyde dehydrogenase (FDH) at a concentration of 0.09 units/ml, and its cofactor, NAD+ at 8.1 mM, during the exposure period. The addition of FDH and NAD+ eliminated the toxicity and dose-dependent increase in mutant frequency (2-18 fold) produced by HCHO in both the nonactivated and S-9 activated assays. Toxicity and mutagenicity of HCHO-releasing species present as contaminants in a polymeric coating and as the active agent in industrial biocides was similarly reduced or eliminated. Mutagenicity unrelated to HCHO was unaffected by the modification. This modified assay can be used to identify HCHO-mediated mutagensis from compounds for which hydrolytic or enymatic release of HCHO can occur. 

ANIMALS; CYTOLOGY; HISTOCYTOCHEMISTRY; GENETICS; CYTOGENETICS; ANIMALS/GENETICS; BIOCHEMISTRY; AMINO ACIDS; PEPTIDES; PROTEINS; POISONING; ANIMALS, LABORATORY; CELL LINE; NEOPLASMS/PATHOLOGY; CARCINOGENS; HERBICIDES; PEST CONTROL; PESTICIDES; MURIDAE; Cytology and Cytochemistry-Animal; Genetics and Cytogenetics-General; Genetics and Cytogenetics-Animal; Biochemical Studies-General; Biochemical Studies-Proteins; Toxicology-General; Neoplasms and Neoplastic Agents-Neoplastic Cell Lines; Neoplasms and Neoplastic Agents-Carcinogens and Carcinogenesis; 50-00-0