Details

Autor(en) / Beteiligte

• Rorije, Emiel
• Muller, André
• Beekhuijzen, Manon E.W.
• Hass, Ulla
• Heinrich-Hirsch, Barbara
• Paparella, Martin
• Schenk, Erna
• Ulbrich, Beate
• Hakkert, Betty C.
• Piersma, Aldert H.

Titel

On the impact of second generation mating and offspring in multi-generation reproductive toxicity studies on classification and labelling of substances in Europe

Ist Teil von

• Regulatory toxicology and pharmacology, 2011-11, Vol.61 (2), p.251-260

Ort / Verlag

Netherlands: Elsevier Inc

Erscheinungsjahr

2011

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• ► The impact of second generation effects on classification and labelling was analysed. ► The second generation was not decisive for 50 classified substances except fenarimol. ► Fenarimol provided endocrine and developmental neurotoxicity alerts. ► In the EOGRTS fenarimol would thus be detected as a developmental neurotoxicant. ► These results support replacement of the 2-generation reprotox study by the EOGRTS. The possible impact on classification and labelling decisions of effects observed in second generation parental (P1) and offspring (F2) parameters in multi-generation studies was investigated. This was done for 50 substances classified as reproductive toxicants in Europe, for which a multi-generation study was available. The P1 and F2 effects were compared to parental (P0) and first generation offspring (F1) effects with regard to type of effect as well as incidence, magnitude and severity (IMS), at any dose level. For every study with unique P1/F2 effects, or differences in IMS, the influence of the P1/F2 findings on the classification decision was investigated. Unique P1/F2 generation findings did not play a crucial role in the classification decision of any of the 50 classified substances, except for fenarimol. This substance however provided abundant alerts on the basis of its endocrine activity and developmental neurotoxicity and would therefore also be expected to be identified as a developmental neurotoxicant in an Extended One Generation Reproductive Toxicity Study (EOGRTS). These findings, in addition to the increased number of parameters analysed, increased statistical power and reduced animal use, provide strong further support for replacement of the classical two-generation reproductive toxicity study by the EOGRTS in regulatory reproductive toxicity assessment.