Cytochrome P450-inhibitory activity of parabens and phthalates used in consumer products

J Toxicol Sci. 2016;41(4):551-60. doi: 10.2131/jts.41.551.


The in vitro cytochrome P450 (CYP)-inhibitory effects of 11 parabens and 7 phthalates used in consumer products, as well as their hydrolytic metabolites, were investigated, using rat liver microsomes as an enzyme source. The effects on individual CYP isozymes were evaluated by assaying inhibition of activities towards specific substrates, i.e., ethoxyresorufin O-dealkylase (EROD), methoxyresorufin O-dealkylase (MROD), pentoxyresorufin O-dealkylase (PROD), 7-benzyloxy-4-trifluoromethylcoumarin dealkylase (BFCD), 7-methoxy-4-trifluoromethylcoumarin dealkylase (MFCD) and 7-ethoxy-4-trifluoromethylcoumarin dealkylase (EFCD) activities. These activities were dose-dependently inhibited, most potently by medium-side-chain parabens (C6-9) and phthalates (C4-6), and less potently by shorter- and longer-side-chain esters. The hydrolytic product of parabens, 4-hydroxybenzoic acid, was not inhibitory, while those of phthalates, phthalic acid monoesters, showed lower inhibitory activity than the parent phthalates. Parabens showed relatively potent inhibition of MFCD activity, considered to be mainly due to CYP2C, and phthalates showed relatively potent inhibition of PROD activity, considered to be mainly due to CYP2B.

MeSH terms

  • Animals
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Biotransformation
  • Consumer Product Safety
  • Cytochrome P-450 Enzyme Inhibitors / metabolism
  • Cytochrome P-450 Enzyme Inhibitors / toxicity*
  • Cytochrome P-450 Enzyme System / metabolism*
  • Dose-Response Relationship, Drug
  • Humans
  • Hydrolysis
  • Isoenzymes
  • Liver / drug effects*
  • Liver / enzymology
  • Male
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology
  • Parabens / metabolism
  • Parabens / toxicity*
  • Phthalic Acids / metabolism
  • Phthalic Acids / toxicity*
  • Rats, Sprague-Dawley
  • Risk Assessment


  • Cytochrome P-450 Enzyme Inhibitors
  • Isoenzymes
  • Parabens
  • Phthalic Acids
  • cytochrome P-450 CYP2C subfamily
  • phthalic acid
  • Cytochrome P-450 Enzyme System
  • Aryl Hydrocarbon Hydroxylases