Genotoxicity and glucose tolerance induction by acetyltriethylcitrate, substitute plasticizer compared to di(2-ethylhexyl)phthalate

Sci Rep. 2019 Aug 22;9(1):12237. doi: 10.1038/s41598-019-48599-y.


As di(2-ethylhexyl) phthalate (DEHP), one of phthalates, is classified as probable human carcinogens in EPA, acetyltriethyl citrate(ATEC), one of aliphatic esters, could be applied to DEHP substitute. ATEC is used as plasticizers in cosmetics and nail products. Here, we studied whether ATEC might have genotoxic potential and induce glucose tolerance as compared to DEHP. Genotoxicity was determined by Ames test with histidine-requiring Salmonella typhimurium (TA98, TA100, TA1535 and TA1537) and tryptophan-requiring Escherichia coli (WP2uvrA(pKM101)) strains, chromosomal aberration assay with Chinese hamster lung(CHL/IU) cells, and micronucleus test with bone marrow cells of CD-1 mice. The number of revertants was not significantly changed in Ames test. The frequency of cells with chromosome aberrations was less than 5% in ATEC- or DEHP-treated cells for 6 or 24 h. In addition, no statistically significant increase was observed for the incidence of micronucleated polychromatic erythrocytes (MNPCE) in polychromatic erythrocytes (PCE) and for the ratio of PCE among total erythrocytes at 24 or 48 h after the treatment of mice with ATEC or DEHP. In the meanwhile, blood glucose level (BGL) was increased by the treatment of mice with DEHP or ATEC for 5 consecutive days. Additional 7 days later, BGL by DEHP was recovered to normal level, but not that by ATEC. Then, taken together, our results suggest that ATEC could disrupt glucose metabolism under our experimental conditions. Therefore, although DEHP and ATEC may not be genotoxic, our data should be helpful for persons with the problem in glucose metabolism to choose products containing DEHP or ATEC.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cricetinae
  • Cricetulus
  • DNA Damage / drug effects*
  • Diethylhexyl Phthalate / toxicity*
  • Escherichia coli / drug effects*
  • Escherichia coli / genetics
  • Glucose / metabolism*
  • Glucose Tolerance Test
  • Mice
  • Mutagenicity Tests
  • Mutagens
  • Plasticizers / toxicity*
  • Salmonella typhimurium / drug effects*
  • Salmonella typhimurium / genetics


  • Mutagens
  • Plasticizers
  • Diethylhexyl Phthalate
  • Glucose