Derivation of a No-significant-risk-level (NSRL) for dermal exposures to diethanolamine

• Published in: Regulatory toxicology and pharmacology 2016-04, Vol.76, p.137-151
• Main Authors: Kirman, C.R., Hughes, B., Becker, R.A., Hays, S.M.
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Animals; Carcinogenicity Tests; Dose-response assessment; Dose-Response Relationship, Drug; Epigenesis, Genetic - drug effects; Ethanolamines - administration & dosage; Ethanolamines - toxicity; Humans; Kidney Neoplasms - chemically induced; Kidney Neoplasms - genetics; Liver Neoplasms - chemically induced; Liver Neoplasms - genetics; Mice; Mode of action; Models, Biological; No-Observed-Adverse-Effect Level; Risk Assessment; Skin - drug effects; Skin - metabolism; Skin Absorption; Species differences; Species Specificity
• ISSN: 0273-2300; 1096-0295
• DOI: 10.1016/j.yrtph.2016.01.020

Diethanolamine (DEA) has been found to produce liver and kidney tumors in mice following lifetime dermal exposures. Data regarding the mode of action by which DEA produces these tumors were used to support a dose-response assessment that resulted in a no-significant-risk-level (NSRL) for dermal exposures to DEA. DEA and its metabolites are structural analogs to endogenous agents important to choline homeostasis. Sufficient information is available to support an epigenetic MOA involving the perturbation of choline homeostasis and hepatic methylation reactions in the formation of mouse liver tumors. This MOA may also apply to mouse kidney tumors, but direct measurements for key events in kidney are lacking. For both tumor types, dose-response data were pooled across four cancer bioassays conducted for DEA and DEA-containing condensates in order to provide a more robust characterization of the dose-response relationships. Doses were expressed in terms of dermally absorbed dose so that the dose-dependency and species differences in the dermal absorption of DEA were addressed. The resulting NSRL value of 3400 ug/day for dermal exposures to DEA is considered to be protective of human health for both tumor endpoints. •NSRL values were derived for dermal exposures to DEA.•Mode of action was used to support decisions in the assessment.•Dose-dependent and species differences in absorption were incorporated.