Retrospective analysis of relative parameter sensitivity in multi-Retrospective analysis ogeneration reproductive toxicity studies
Dang, Z; Rorije, E; Esch, T; Muller, A; Hakkert, B; Piersma, A
| HERO ID | 697706 |
|---|---|
| In Press | No |
| Year | 2009 |
| Title | Retrospective analysis of relative parameter sensitivity in multi-Retrospective analysis ogeneration reproductive toxicity studies |
| Authors | Dang, Z; Rorije, E; Esch, T; Muller, A; Hakkert, B; Piersma, A |
| Journal | Reproductive Toxicology |
| Volume | 28 |
| Issue | 2 |
| Page Numbers | 196-202 |
| Abstract | Current suggestions towards amending the OECD two-generation protocol include omission of the second generation and inclusion of additional parameters. This study analysed the relative parameter sensitivity in 18 individually published multi-generation studies with substances toxic to fertility. Among parameters that most often determined the reproductive LOAEL were weight of testis, dam and pup as well as litter size. Several other parameters were found to be unaffected in all studies evaluated. Some substances affected a specific set of parameters, indicating that rarely affected parameters may prove crucial in individual situations. This argues for the inclusion of a wide spectrum of parameters to cover all possible effects. Less sensitive parameters, mechanistically related to more sensitive ones, may be omitted as they will unlikely contribute to the overall LOAEL. This study gives first insights and needs follow-up by more extensive analyses before firm conclusions on the design of the two-generation study protocol can be drawn. |
| Doi | 10.1016/j.reprotox.2009.04.009 |
| Pmid | 19393313 |
| Wosid | WOS:000268849700010 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Source: Web of Science WOS:000268849700010 |
| Is Public | Yes |
| Language Text | English |
| Keyword | OECD416; Continuous breeding; Sensitive reproductive endpoints; LOAELs; Risk assessment; Classification and labelling; Fertility; Offspring |
| Is Qa | No |
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