Combined retrospective analysis of 498 rat multi-generation reproductive toxicity studies: on the impact of parameters related to F1 mating and F2 offspring

A.H. Piersma; E. Rorije; MEW Beekhuijzen; R. Cooper; D.J. Dix; B. Heinrich-Hirsch; M. Martin; E. Mendez; A. Muller; M. Paparella; D. Ramsingh; E. Reaves; P. Ridgway; E. Schenk; L. Stachiw; B. Ulbrich; B.C. Hakkert

doi:10.1016/j.reprotox.2010.11.013

Combined retrospective analysis of 498 rat multi-generation reproductive toxicity studies: on the impact of parameters related to F1 mating and F2 offspring

A.H. Piersma
, E. Rorije
, MEW Beekhuijzen
, R. Cooper
, D.J. Dix
, B. Heinrich-Hirsch
, M. Martin
, E. Mendez
, A. Muller
, M. Paparella
, D. Ramsingh
, E. Reaves
, P. Ridgway
, E. Schenk
, L. Stachiw
, B. Ulbrich
, B.C. Hakkert

extern

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

The multi-generation reproductive toxicity study (OECD TG 416 and USEPA 870.3800) has been extensively used internationally to assess the adverse effects of substances on reproduction. Recently the necessity of producing a second generation to assess the potential for human health risks has been questioned. The present standardized retrospective analysis of the impact of the second generation on overall study outcome combines earlier analyses and includes 498 rat multi-generation studies representing 438 different tested substances. Detailed assessment of study reports revealed no critical differences in sensitivities between the generations on the basis of a consideration of all endpoints evaluated. This analysis indicates that the second generation mating and offspring will very rarely provide critical information. These findings are consistent with the conclusions of previous retrospective analyses conducted by RIVM, USEPA and PMRA and support adoption of the proposed OECD extended one-generation reproductive toxicity study protocol in regulatory risk assessment testing strategies.

Original language	Undefined/Unknown
Pages (from-to)	392-401
Number of pages	10
Journal	Reproductive Toxicology
Volume	31
Issue number	4
DOIs	https://doi.org/10.1016/j.reprotox.2010.11.013
Publication status	Published - 2011

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Access to Document

10.1016/j.reprotox.2010.11.013

Cite this

Piersma, A. H., Rorije, E., Beekhuijzen, MEW., Cooper, R., Dix, D. J., Heinrich-Hirsch, B., Martin, M., Mendez, E., Muller, A., Paparella, M., Ramsingh, D., Reaves, E., Ridgway, P., Schenk, E., Stachiw, L., Ulbrich, B., & Hakkert, B. C. (2011). Combined retrospective analysis of 498 rat multi-generation reproductive toxicity studies: on the impact of parameters related to F1 mating and F2 offspring. Reproductive Toxicology, 31(4), 392-401. https://doi.org/10.1016/j.reprotox.2010.11.013

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abstract = "The multi-generation reproductive toxicity study (OECD TG 416 and USEPA 870.3800) has been extensively used internationally to assess the adverse effects of substances on reproduction. Recently the necessity of producing a second generation to assess the potential for human health risks has been questioned. The present standardized retrospective analysis of the impact of the second generation on overall study outcome combines earlier analyses and includes 498 rat multi-generation studies representing 438 different tested substances. Detailed assessment of study reports revealed no critical differences in sensitivities between the generations on the basis of a consideration of all endpoints evaluated. This analysis indicates that the second generation mating and offspring will very rarely provide critical information. These findings are consistent with the conclusions of previous retrospective analyses conducted by RIVM, USEPA and PMRA and support adoption of the proposed OECD extended one-generation reproductive toxicity study protocol in regulatory risk assessment testing strategies.",

author = "A.H. Piersma and E. Rorije and MEW Beekhuijzen and R. Cooper and D.J. Dix and B. Heinrich-Hirsch and M. Martin and E. Mendez and A. Muller and M. Paparella and D. Ramsingh and E. Reaves and P. Ridgway and E. Schenk and L. Stachiw and B. Ulbrich and B.C. Hakkert",

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Piersma, AH, Rorije, E, Beekhuijzen, MEW, Cooper, R, Dix, DJ, Heinrich-Hirsch, B, Martin, M, Mendez, E, Muller, A, Paparella, M, Ramsingh, D, Reaves, E, Ridgway, P, Schenk, E, Stachiw, L, Ulbrich, B & Hakkert, BC 2011, 'Combined retrospective analysis of 498 rat multi-generation reproductive toxicity studies: on the impact of parameters related to F1 mating and F2 offspring', Reproductive Toxicology, vol. 31, no. 4, pp. 392-401. https://doi.org/10.1016/j.reprotox.2010.11.013

TY - JOUR

T1 - Combined retrospective analysis of 498 rat multi-generation reproductive toxicity studies: on the impact of parameters related to F1 mating and F2 offspring

AU - Piersma, A.H.

AU - Rorije, E.

AU - Beekhuijzen, MEW

AU - Cooper, R.

AU - Dix, D.J.

AU - Heinrich-Hirsch, B.

AU - Martin, M.

AU - Mendez, E.

AU - Muller, A.

AU - Paparella, M.

AU - Ramsingh, D.

AU - Reaves, E.

AU - Ridgway, P.

AU - Schenk, E.

AU - Stachiw, L.

AU - Ulbrich, B.

AU - Hakkert, B.C.

PY - 2011

Y1 - 2011

N2 - The multi-generation reproductive toxicity study (OECD TG 416 and USEPA 870.3800) has been extensively used internationally to assess the adverse effects of substances on reproduction. Recently the necessity of producing a second generation to assess the potential for human health risks has been questioned. The present standardized retrospective analysis of the impact of the second generation on overall study outcome combines earlier analyses and includes 498 rat multi-generation studies representing 438 different tested substances. Detailed assessment of study reports revealed no critical differences in sensitivities between the generations on the basis of a consideration of all endpoints evaluated. This analysis indicates that the second generation mating and offspring will very rarely provide critical information. These findings are consistent with the conclusions of previous retrospective analyses conducted by RIVM, USEPA and PMRA and support adoption of the proposed OECD extended one-generation reproductive toxicity study protocol in regulatory risk assessment testing strategies.

AB - The multi-generation reproductive toxicity study (OECD TG 416 and USEPA 870.3800) has been extensively used internationally to assess the adverse effects of substances on reproduction. Recently the necessity of producing a second generation to assess the potential for human health risks has been questioned. The present standardized retrospective analysis of the impact of the second generation on overall study outcome combines earlier analyses and includes 498 rat multi-generation studies representing 438 different tested substances. Detailed assessment of study reports revealed no critical differences in sensitivities between the generations on the basis of a consideration of all endpoints evaluated. This analysis indicates that the second generation mating and offspring will very rarely provide critical information. These findings are consistent with the conclusions of previous retrospective analyses conducted by RIVM, USEPA and PMRA and support adoption of the proposed OECD extended one-generation reproductive toxicity study protocol in regulatory risk assessment testing strategies.

U2 - 10.1016/j.reprotox.2010.11.013

DO - 10.1016/j.reprotox.2010.11.013

M3 - Article

SN - 0890-6238

VL - 31

SP - 392

EP - 401

JO - Reproductive Toxicology

JF - Reproductive Toxicology

IS - 4

ER -