Scientific issues associated with the validation of in vitro and in vivo methods for assessing endocrine disrupting chemicals.
The assays required to assess the potential of chemicals to act as endocrine disrupting (ED) agents are either in place or are under current development. However, the validation and utilisation of these assays is currently being hampered by uncertainties regarding their purpose and required sensitivity, and uncertainties as to the intrinsic variability of the parameters being measured. This article discusses these several sources of uncertainty and the intrinsic variability of many of the key assay parameters. It is concluded that current uncertainties regarding the use of ED assays, and the extrapolation of rodent effects to humans, are due to the absence of an extensive agreed rodent control database for the developmental parameters under study, coupled to the established intrinsic variability of these parameters between strains/species of test animals and test protocols. Only when these factors are generally accepted, well studied and controlled for, will it be possible to employ ED assays with confidence and to relate assay data to effects likely to be seen in humans.
Ashby
John
J
Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield, SK10 4TJ Cheshire, UK. john.ashby@syngenta.com
D000818:Animals; D001559:Benzhydryl Compounds; D001681:Biological Assay; D004032:Diet; D004054:Diethylstilbestrol / Q000633:toxicity; D004702:Endocrine Glands / Q000187:drug effects* / Q000473:pathology; D004700:Endocrine System Diseases / Q000139:chemically induced* / Q000473:pathology; D004968:Estrogens, Non-Steroidal / Q000633:toxicity; D006801:Humans; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010636:Phenols / Q000633:toxicity; D051381:Rats; D015203:Reproducibility of Results; D015262:Xenobiotics / Q000633:toxicity*; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004054:Diethylstilbestrol; D004968:Estrogens, Non-Steroidal; D010636:Phenols; D015262:Xenobiotics; C006780:bisphenol A; D000098826:Bisphenol A Compounds