Incorporating ToxCast™ data into naphthalene human health risk assessment.

Autor: Bailey LA; Gradient, One Beacon Street, Boston, MA 02108, United States of America. Electronic address: lbailey@gradientcorp.com., Rhomberg LR; Gradient, One Beacon Street, Boston, MA 02108, United States of America.
Jazyk: angličtina
Zdroj: Toxicology in vitro : an international journal published in association with BIBRA [Toxicol In Vitro] 2020 Sep; Vol. 67, pp. 104913. Date of Electronic Publication: 2020 Jun 09.
DOI: 10.1016/j.tiv.2020.104913
Abstrakt: Chronic inhalation of naphthalene causes nasal olfactory epithelial tumors in rats and benign lung adenomas in mice. The available human data do not establish an association between naphthalene and increased respiratory cancer risk. Therefore, cancer risk assessment of naphthalene in humans depends predominantly on experimental evidence from rodents. The United States Environmental Protection Agency's (US EPA) Toxicity Forecaster (ToxCast™) database contains data from 710 in vitro assays for naphthalene, the majority of which were conducted in human cells. Of these assays, only 18 were active for naphthalene, and all were in human liver cells. No assays were active in human bronchial epithelial cells. In our analysis, all of the active naphthalene ToxCast assay data were reviewed and used to: 1) determine naphthalene human inhalation concentrations corresponding to relevant activity concentrations for all active naphthalene assays, using a physiologically based pharmacokinetic (PBPK) model; and 2) evaluate the transcriptional responses for active assays in the context of consistency with the larger naphthalene data set and proposed modes of action (MoAs) for naphthalene toxicity and carcinogenicity. The transcriptional responses in liver cells largely reflect cellular activities related to oxidative stress and chronic inflammation. Overall, the results from our analysis of the active ToxCast assays for naphthalene are consistent with conclusions from our earlier weight-of-evidence evaluation for naphthalene carcinogenesis.
Competing Interests: Declaration of Competing Interest The authors' affiliation during the course of this work is as shown on the first page. This paper was prepared with financial support to Gradient from the American Petroleum Institute (API). The work reported in the paper was conducted during the normal course of employment by Gradient. The API was given the opportunity to comment on the manuscript. The authors retained final decision-making and have the sole responsibility for the writing and content of this paper. The views and opinions expressed are not necessarily those of API.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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