Journal
TOXICOLOGY
Volume 458, Issue -, Pages -Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2021.152839
Keywords
Immunoaffinity-based mass spectrometry; Pesticide mixtures; HepaRG cells; Liver toxicity; Multiple linear regression analysis; Biomarker
Categories
Funding
- German Federal Ministry of Education and Research (BMBF), (e:TOP
- Combiomics 2) [031L0118A/B/C]
Ask authors/readers for more resources
Toxicological effects of chemicals are often tested individually, while consumers are actually exposed to complex mixtures like multiple pesticide residues. Researching the combined effects of pesticides can provide a more comprehensive understanding of their impact on animals and humans.
Toxicological effects of chemicals are mostly tested individually. However, consumers encounter exposure to complex mixtures, for example multiple pesticide residues, by consuming food such as crops, fruits or vegetables. Currently, more than 450 active substances are approved in the European Union, and there is little data on effects after combined exposure to several pesticides. Toxicological animal studies would increase enormously, if pesticide combinations had to be analyzed in vivo. Therefore, in vitro methods addressing this issue are needed. We have developed 32 immunoaffinity-based mass spectrometry assays to investigate the impact of hepatotoxic active substances on liver proteins in human HepaRG cells. Five compounds were selected based on their (dis) similar capability to modulate protein levels, and on their combined use in commercially available formulations. Four binary mixtures were prepared from these five substances and tested in different concentrations over three time points. We applied a novel statistical method to describe deviations from additivity and to detect antagonistic and synergistic effects. The results regarding the abundance of hepatotoxicity-related proteins showed additive behavior for 1323 out of 1427 endpoints tested, while 104 combinatorial effects deviating from additivity, such as antagonism or synergism were observed.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available