Different DNA damage response of cis and trans isomers of commonly used UV filter after the exposure on adult human liver stem cells and human lymphoblastoid cells

Anežka Sharma; Katarína Bányiová; Pavel Babica; Naouale El Yamani; Andrew Richard Collins; Pavel Čupr

doi:10.1016/j.scitotenv.2017.03.043

Different DNA damage response of cis and trans isomers of commonly used UV filter after the exposure on adult human liver stem cells and human lymphoblastoid cells

Sci Total Environ. 2017 Sep 1:593-594:18-26. doi: 10.1016/j.scitotenv.2017.03.043. Epub 2017 Mar 21.

Authors

Anežka Sharma¹, Katarína Bányiová¹, Pavel Babica¹, Naouale El Yamani², Andrew Richard Collins³, Pavel Čupr⁴

Affiliations

¹ Masaryk University, Faculty of Science, RECETOX, Research Centre for Toxic Compounds in the Environment, Kamenice 753/5, 625 00 Brno, Czech Republic.
² Department of Nutrition, University of Oslo, PO Box 1046, Blindern, N-0316 Oslo, Norway; Department of Environmental Chemistry, Health Effect Laboratory, NILU-Norwegian Institute for Air Research, Instituttveien 18, 2007 Kjeller, Norway.
³ Department of Nutrition, University of Oslo, PO Box 1046, Blindern, N-0316 Oslo, Norway.
⁴ Masaryk University, Faculty of Science, RECETOX, Research Centre for Toxic Compounds in the Environment, Kamenice 753/5, 625 00 Brno, Czech Republic. Electronic address: cupr@recetox.muni.cz.

PMID: 28340478
DOI: 10.1016/j.scitotenv.2017.03.043

Abstract

2-ethylhexyl 4-methoxycinnamate (EHMC), used in many categories of personal care products (PCPs), is one of the most discussed ultraviolet filters because of its endocrine-disrupting effects. EHMC is unstable in sunlight and can be transformed from trans-EHMC to emergent cis-EHMC. Toxicological studies are focusing only on trans-EHMC; thus the toxicological data for cis-EHMC are missing. In this study, the in vitro genotoxic effects of trans- and cis-EHMC on adult human liver stem cells HL1-hT1 and human-derived lymphoblastoid cells TK-6 using a high-throughput comet assay were studied. TK-6 cells treated with cis-EHMC showed a high level of DNA damage when compared to untreated cells in concentrations 1.56 to 25μgmL^-1. trans-EHMC showed genotoxicity after exposure to the two highest concentrations 12.5 and 25μgmL^-1. The increase in DNA damage on HL1-hT1 cells induced by cis-EHMC and trans-EHMC was detected at the concentration 25μgmL^-1. The No observed adverse effect level (NOAEL, mg kg^-1bwday^-1) was determined using a Quantitative in vitro to in vivo extrapolation (QIVIVE) approach: NOAEL_trans-EHMC=3.07, NOAEL_cis-EHMC=0.30 for TK-6 and NOAEL_trans-EHMC=26.46, NOAEL_cis-EHMC=20.36 for HL1-hT1. The hazard index (HI) was evaluated by comparing the reference dose (RfD, mgkg^-1bwday^-1) obtained from our experimental data with the chronic daily intake (CDI) of the female population. Using comet assay experimental data with the more sensitive TK-6 cells, HI_cis-EHMC was 7 times higher than HI_trans-EHMC. In terms of CDI, relative contributions were; dermal exposure route>oral>inhalation. According to our results we recommend the RfD_trans-EHMC=0.20 and RfD_cis-EHMC=0.02 for trans-EHMC and cis-EHMC, respectively, to use for human health risk assessment. The significant difference in trans-EHMC and cis-EHMC response points to the need for toxicological reevaluation and application reassessment of both isomers in PCPs.

Keywords: Adult human liver stem cells; Genotoxicity; High-throughput comet assay; Human risk assessment; Isomerization; trans/cis-EHMC.

MeSH terms

Cell Line
Cinnamates / adverse effects*
Cosmetics / adverse effects
DNA Damage*
Female
Humans
Liver / cytology
Lymphocytes / drug effects*
Risk Assessment
Stem Cells / drug effects*
Sunlight
Sunscreening Agents / adverse effects*

Substances

Cinnamates
Cosmetics
Sunscreening Agents
ethyl 4-methoxycinnamate