Risk assessments for chronic exposure of children and prospective parents to ethylbenzene (CAS No. 100-41-4)

Abstract

Potential chronic health risks for children and prospective parents exposed to ethylbenzene were evaluated in response to the Voluntary Children's Chemical Evaluation Program. Ethylbenzene exposure was found to be predominately via inhalation with recent data demonstrating continuing decreases in releases and both outdoor and indoor concentrations over the past several decades. The proportion of ethylbenzene in ambient air that is attributable to the ethylbenzene/styrene chain of commerce appears to be relatively very small, less than 0.1% based on recent relative emission estimates. Toxicity reference values were derived from the available data, with physiologically based pharmacokinetic models and benchmark dose methods used to assess dose–response relationships. An inhalation non-cancer reference concentration or RfC of 0.3 parts per million (ppm) was derived based on ototoxicity. Similarly, an oral non-cancer reference dose or RfD of 0.5 mg/kg body weight/day was derived based on liver effects. For the cancer assessment, emphasis was placed upon mode of action information. Three of four rodent tumor types were determined not to be relevant to human health. A cancer reference value of 0.48 ppm was derived based on mouse lung tumors. The risk characterization for ethylbenzene indicated that even the most highly exposed children and prospective parents are not at risk for non-cancer or cancer effects of ethylbenzene.

Keywords:

• cancer
• exposure assessment
• hepatotoxicity
• mode of action
• ototoxicity

Acknowledgments

Dr. Sweeney acknowledges with gratitude the helpful insights on dopamine and pituitary hyperplasia provided by Dr. Joyce Rohan of the Naval Medical Research Unit--Dayton The authors would like to convey their appreciation for the thorough and helpful comments provided by the five anonymous reviewers selected by the Editor.

Declaration of interest

This work was sponsored by the American Chemistry Council's Ethylbenzene VCCEP Panel. The members of this panel are Chevron Phillips Chemical Company, the Dow Chemical Company, GE Plastics, INEOS Styrenics (formerly BP Amoco Chemical Company), Lyondell Chemical Company, NOVA Chemicals Inc., Sterling Chemicals Inc., and TOTAL Petrochemicals USA Inc. (formerly ATOFINA Petrochemicals Inc.). Updates to the exposure assessment were funded by the SIRC.

The vast majority of this effort was conducted while the authors were employed by the organizations listed on the cover page. Dr. Sweeney and Mr. Kirman performed minor updates while with their current employers the Henry M. Jackson Foundation for the Advancement of Military Medicine (LMS) and Summit Toxicology (CRK). Dr. Sweeney's update efforts were supported by Work Unit Number 60769.

The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the US Government. Authors include employees or contract employees of the US Government. This work was prepared as part of their official duties. Title 17 U.S.C. §105 provides that “Copyright protection under this title is not available for any work of the United States Government.” Title 17 U.S.C. §101 defines a US Government work as a work prepared by a military service member or employee of the US Government as part of that person's official duties.

Supplementary materials available online

Supplementary Material, Supplement A, B and C to be found online at http://informahealthcare.com/doi/abs/10.3109/10408444.2015.1046157.