Rodent carcinogenicity tests need be no longer than 18 months: an analysis based on 210 chemicals in the IARC monographs.
The IARC Monographs (Vols 1-70) were studied to determine the time of onset of treatment-related tumorigenicity in long-term rodent studies for chemicals classified by IARC as having sufficient evidence of carcinogenicity in animals. The analysis excluded studies on metals and their salts, studies on particulates, studies by parenteral routes of administration that resulted in tumours only at the site of exposure, and studies that did not approximate to the current standard long-term rodent carcinogenicity bioassay, for instance transplacental or multigeneration studies, initiator-promoter studies, lung tumour assays in Strain A mice and studies in newborn animals. Data from a total of 210 chemicals revealed that, overall, evidence of treatment-related tumorigenicity was first apparent within 12 months for 66% of the chemicals and for only 7% were studies of longer than 18 months necessary. All IARC Group 1 chemicals were detected in animals within 18 months, and most within 12 months. Most of the tumour types that required more than 18 months for detection were of dubious relevance to human risk assessment. Termination of rodent carcinogenicity studies at 18 months or earlier would greatly reduce the complications that arise in interpreting the findings in aged animals which often have defective hepatic or renal function and would also markedly reduce the time required for histopathological examination of dozens of tissues taken from the approximately 500 animals routinely employed in these studies.
Davies
T S
TS
Pfizer Central Research, Groton, CT 06340, USA.
Lynch
B S
BS
Monro
A M
AM
Munro
I C
IC
Nestmann
E R
ER
D000818:Animals; D015197:Carcinogenicity Tests / Q000592:standards*; D002273:Carcinogens / Q000633:toxicity*; D006801:Humans; D051379:Mice; D011786:Quality Control; D051381:Rats; D015203:Reproducibility of Results; D012107:Research Design; D018570:Risk Assessment; D013997:Time Factors
D002273:Carcinogens