Investigating Molecular Mechanisms of Immunotoxicity and the Utility of ToxCast for Immunotoxicity Screening of Chemicals Added to Food

Olga V. Naidenko, David Q. Andrews, Alexis M. Temkin, Tasha Stoiber, Uloma Igara Uche, Sydney Evans and Sean Perrone-Gray
Additional contact information
Olga V. Naidenko: Environmental Working Group, 1436 U Street NW, Suite 100, Washington, DC 20009, USA
David Q. Andrews: Environmental Working Group, 1436 U Street NW, Suite 100, Washington, DC 20009, USA
Alexis M. Temkin: Environmental Working Group, 1436 U Street NW, Suite 100, Washington, DC 20009, USA
Tasha Stoiber: Environmental Working Group, 1436 U Street NW, Suite 100, Washington, DC 20009, USA
Uloma Igara Uche: Environmental Working Group, 1436 U Street NW, Suite 100, Washington, DC 20009, USA
Sydney Evans: Environmental Working Group, 1436 U Street NW, Suite 100, Washington, DC 20009, USA
Sean Perrone-Gray: Environmental Working Group, 1436 U Street NW, Suite 100, Washington, DC 20009, USA

IJERPH, 2021, vol. 18, issue 7, 1-24

Abstract: The development of high-throughput screening methodologies may decrease the need for laboratory animals for toxicity testing. Here, we investigate the potential of assessing immunotoxicity with high-throughput screening data from the U.S. Environmental Protection Agency ToxCast program. As case studies, we analyzed the most common chemicals added to food as well as per- and polyfluoroalkyl substances (PFAS) shown to migrate to food from packaging materials or processing equipment. The antioxidant preservative tert-butylhydroquinone (TBHQ) showed activity both in ToxCast assays and in classical immunological assays, suggesting that it may affect the immune response in people. From the PFAS group, we identified eight substances that can migrate from food contact materials and have ToxCast data. In epidemiological and toxicological studies, PFAS suppress the immune system and decrease the response to vaccination. However, most PFAS show weak or no activity in immune-related ToxCast assays. This lack of concordance between toxicological and high-throughput data for common PFAS indicates the current limitations of in vitro screening for analyzing immunotoxicity. High-throughput in vitro assays show promise for providing mechanistic data relevant for immune risk assessment. In contrast, the lack of immune-specific activity in the existing high-throughput assays cannot validate the safety of a chemical for the immune system.

Keywords: immunotoxicology; multi-omics approaches in immunotoxicology; immunotoxic aspects of food additives; high-throughput screening; ToxCast; food additive; food contact substance; tert-butylhydroquinone; per- and polyfluoroalkyl substances (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2021
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.mdpi.com/1660-4601/18/7/3332/pdf (application/pdf)
https://www.mdpi.com/1660-4601/18/7/3332/ (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:gam:jijerp:v:18:y:2021:i:7:p:3332-:d:523006

Access Statistics for this article

IJERPH is currently edited by Ms. Jenna Liu

More articles in IJERPH from MDPI
Bibliographic data for series maintained by MDPI Indexing Manager ().