Toxicity of compounds with endocrine activity in the OECD 421 reproductive toxicity screening test
Toxiciteit van hormoonontregelaars in de OECD 421 screeningstest voor reproductietoxiciteit
26 May 2012, PDF |
26 pages |
Piersma AH, Verhoef A, Elvers LH, Wester PW
RIVM Report 650030002
The issue of endocrine disruption has, in view of human risk assessment, raised the question on whether more sensitive test methods are needed to detect the reproductive toxic properties of xenobiotic compounds with endocrine properties. We studied six known and alleged endocrine disruptors in an existing reproductive toxicology screening test to see if this test would score these compounds as reproductive toxicants. The protocol involves parental dosage from two weeks prenatally to 6 days postnatally for dams, and a total of 28 days exposure in sires. Compounds tested were the contraceptive Ethynylestradiol, the phytoestrogen Coumestrol, the surfactant 4-Tert-octylphenol, the plastic monomer Bisphenol A, the fungicide Vinclozolin, and the plasticizer Butylbenzylphthalate. Compound dosage was chosen on the basis of relative potency at the estrogen receptor level. Therefore, apart from ethynylestradiol all compounds were tested at dosages much higher than any likely exposure to be expected in humans. Five compounds were clearly scored as reproductive toxicants, affecting one or more parameters such as fertility, luteinization, spermatogenesis and fetal development. 4-Tert-octylphenol appeared lethal at the dosage selected and had little effect at a tenfold lower dosage. These data suggest that endocrine disruptors are likely to be effective in existing reproductive toxicity test systems used for human risk evaluation. Endocrine properties of xenobiotic compounds, assessed at the hormone receptor level, should be combined with in vivo data on their reproductive and general toxicity for proper risk evaluation and risk management of these compounds.