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A M Monro

Publications and source records attributed to A M Monro.

40 records · Page 3Linked to original sources
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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.

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PubMedDate not supplied

Evaluation of the toxicity of drug residues in food: the case for 'relay' toxicity studies.

The tissue residues of veterinary drugs given to food-producing animals are an ill-defined mosaic of parent drug and metabolites. Consumers are only ever exposed to this mixture in the presence of a vast excess of the excipient, food. Given the modifying effects of food on the absorption and disposition of co-administered xenobiotics, it follows that the toxicity of these residues can only be properly evaluated in the presence of a large excess of food. Adoption of a relay toxicity strategy addresses these two points. The proposed relay toxicity testing approach is as follows. The target species receives a recommended dosage regimen of the drug, but a dose level three- to five-fold higher than normal and the animals are then killed several days earlier than the projected withdrawal period. The tissues from these animals, containing the residue mixture at artificially high concentrations, are then administered to laboratory animals for conventional toxicological evaluation. In this approach the residues do not require individual identification and their potential toxicity is evaluated in the presence of the inescapable excipient, food. Determination of an 'exposure' level without observerable toxicity provides, in principle, the means of relating human safety to a No-Observed Effect Level in laboratory animals in the traditional manner.

Animals↗