Application of benchmark dose risk assessment methodology to developmental toxicity: an industrial view.


:The U.S. EPA first signalled its intention to use benchmark dose risk techniques in 1991. Subsequently, publication of draft Guidelines for the Risk Assessment of Reproductive Toxicity data indicated the Agency's intention for wide use of the technique. In developmental toxicity experiments, a number of factors need to be considered before attempting benchmark dose calculations, as compared to the conventional NOAEL approach. For example, care in the assessment of potential litter effects (the litter is the unit of such a study) on the data and whether the data are continuous (e.g. foetal body weight) or discontinuous (e.g. specific or grouped developmental defects where the abnormality is present or absent). Two examples of the use of the benchmark dose approach will be made. First, in the analysis of foetal body weight, where a benchmark dose estimate for an agent producing a 5% decrease in mean foetal weight may be calculated from a shift in the distribution of foetal weights between groups, or by conversion of data to reflect changes in the incidence of 'small' pups (i.e. those towards the extreme of the normal range). The second example involves studies conducted on the developmental toxicity of a triazole antifungal. In the first study, the agent was clearly teratogenic, but a NOAEL was not established and thus necessitated a second study. Analysis of benchmark does estimates (e.g. for % foetuses malformed) from the first study indicated that these were not significantly changed when the data from the second study were combined (i.e. the second study did not aid the risk assessment). The benchmark dose approach has significant scientific and practical advantages over the conventional NOAEL methodology in risk assessments derived from developmental toxicity studies.


Toxicol Lett


Toxicology letters


Foster PM,Auton TR




Has Abstract


1995-12-01 00:00:00












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    journal_title:Toxicology letters

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  • Furocoumarins affect hepatic cytochrome P450 and renal organic ion transporters in mice.

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    journal_title:Toxicology letters

    pub_type: 杂志文章


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    pub_type: 杂志文章


    authors: Yoon S,Han S,Jeon KJ,Kwon S

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    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Saibara T,Toda K,Wakatsuki A,Ogawa Y,Ono M,Onishi S

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    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Hugo P,Bernier J,Krzystyniak K,Potworowski EF,Fournier M

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