Influence of Distribution of Animals between Dose Groups on Estimated Benchmark Dose and Animal Distress for Quantal Responses

Increasingly, dose‐response data are being evaluated with the benchmark dose (BMD) approach rather than by the less precise no‐observed‐adverse‐effect‐level (NOAEL) approach. However, the basis for designing animal experiments, using equally sized dose groups, is still primed for the NOAEL approach....

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Bibliographic Details
Published in:Risk analysis 2017-09, Vol.37 (9), p.1716-1728
Main Authors: Kalantari, Fereshteh, Ringblom, Joakim, Sand, Salomon, Öberg, Mattias
Format: Article
Language:English
Subjects:
Animal distress
animal distribution
Animal research
Animals
benchmark dose
Benchmarks
Bone mineral density
Computer simulation
Design
Design standards
Distributing
Dosage
Monte Carlo simulation
Psychological distress
Risk assessment
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Summary:Increasingly, dose‐response data are being evaluated with the benchmark dose (BMD) approach rather than by the less precise no‐observed‐adverse‐effect‐level (NOAEL) approach. However, the basis for designing animal experiments, using equally sized dose groups, is still primed for the NOAEL approach. The major objective here was to assess the impact of using dose groups of unequal size on both the quality of the BMD and overall animal distress. We examined study designs with a total number of 200 animals distributed in four dose groups employing quantal data generated by Monte Carlo simulations. Placing more animals at doses close to the targeted BMD provided an estimate of BMD that was slightly better than the standard design with equally sized dose groups. In situations involving a clear dose‐response, this translates into fewer animals receiving high doses and thus less overall animal distress. Accordingly, in connection with risk and safety assessment, animal distress can potentially be reduced by distributing the animals appropriately between dose groups without decreasing the quality of the information obtained.
ISSN:0272-4332
1539-6924
DOI:10.1111/risa.12741