Cargando…
Investigating Molecular Mechanisms of Immunotoxicity and the Utility of ToxCast for Immunotoxicity Screening of Chemicals Added to Food
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 stud...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036665/ https://www.ncbi.nlm.nih.gov/pubmed/33804855 http://dx.doi.org/10.3390/ijerph18073332 |
_version_ | 1783676963473326080 |
---|---|
author | Naidenko, Olga V. Andrews, David Q. Temkin, Alexis M. Stoiber, Tasha Uche, Uloma Igara Evans, Sydney Perrone-Gray, Sean |
author_facet | Naidenko, Olga V. Andrews, David Q. Temkin, Alexis M. Stoiber, Tasha Uche, Uloma Igara Evans, Sydney Perrone-Gray, Sean |
author_sort | Naidenko, Olga V. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8036665 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-80366652021-04-12 Investigating Molecular Mechanisms of Immunotoxicity and the Utility of ToxCast for Immunotoxicity Screening of Chemicals Added to Food Naidenko, Olga V. Andrews, David Q. Temkin, Alexis M. Stoiber, Tasha Uche, Uloma Igara Evans, Sydney Perrone-Gray, Sean Int J Environ Res Public Health Article 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. MDPI 2021-03-24 /pmc/articles/PMC8036665/ /pubmed/33804855 http://dx.doi.org/10.3390/ijerph18073332 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ). |
spellingShingle | Article Naidenko, Olga V. Andrews, David Q. Temkin, Alexis M. Stoiber, Tasha Uche, Uloma Igara Evans, Sydney Perrone-Gray, Sean Investigating Molecular Mechanisms of Immunotoxicity and the Utility of ToxCast for Immunotoxicity Screening of Chemicals Added to Food |
title | Investigating Molecular Mechanisms of Immunotoxicity and the Utility of ToxCast for Immunotoxicity Screening of Chemicals Added to Food |
title_full | Investigating Molecular Mechanisms of Immunotoxicity and the Utility of ToxCast for Immunotoxicity Screening of Chemicals Added to Food |
title_fullStr | Investigating Molecular Mechanisms of Immunotoxicity and the Utility of ToxCast for Immunotoxicity Screening of Chemicals Added to Food |
title_full_unstemmed | Investigating Molecular Mechanisms of Immunotoxicity and the Utility of ToxCast for Immunotoxicity Screening of Chemicals Added to Food |
title_short | Investigating Molecular Mechanisms of Immunotoxicity and the Utility of ToxCast for Immunotoxicity Screening of Chemicals Added to Food |
title_sort | investigating molecular mechanisms of immunotoxicity and the utility of toxcast for immunotoxicity screening of chemicals added to food |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036665/ https://www.ncbi.nlm.nih.gov/pubmed/33804855 http://dx.doi.org/10.3390/ijerph18073332 |
work_keys_str_mv | AT naidenkoolgav investigatingmolecularmechanismsofimmunotoxicityandtheutilityoftoxcastforimmunotoxicityscreeningofchemicalsaddedtofood AT andrewsdavidq investigatingmolecularmechanismsofimmunotoxicityandtheutilityoftoxcastforimmunotoxicityscreeningofchemicalsaddedtofood AT temkinalexism investigatingmolecularmechanismsofimmunotoxicityandtheutilityoftoxcastforimmunotoxicityscreeningofchemicalsaddedtofood AT stoibertasha investigatingmolecularmechanismsofimmunotoxicityandtheutilityoftoxcastforimmunotoxicityscreeningofchemicalsaddedtofood AT ucheulomaigara investigatingmolecularmechanismsofimmunotoxicityandtheutilityoftoxcastforimmunotoxicityscreeningofchemicalsaddedtofood AT evanssydney investigatingmolecularmechanismsofimmunotoxicityandtheutilityoftoxcastforimmunotoxicityscreeningofchemicalsaddedtofood AT perronegraysean investigatingmolecularmechanismsofimmunotoxicityandtheutilityoftoxcastforimmunotoxicityscreeningofchemicalsaddedtofood |