1988; Kingsbury, 1964). In addition, there are five volumes of proceedings of international symposia on poisonous plants, with particular emphasis on livestock poisonings (Colegate and Dorling, 1994; Garland and Barr, 1998; James et al., 1992; Keeler et al., 1978; Seawright et al., 1985).
Most of the available veterinary toxicology reports are observational and not experimental, and the relevance of various species of livestock to human toxicity is not well established. Nevertheless, veterinary toxicology information may be quite useful when it corroborates concerns raised by other types of data. Independent of other types of data, evidence of harm in livestock and other veterinary toxicology information is appropriate to consider as a signal prompting an initial review of an ingredient. In addition, the veterinary toxicology literature is also useful for generating hypotheses in need of testing in well-established animal models. A careful mechanism for ensuring continuing awareness by FDA of this important data source is suggested.
The degree of potential human risk is a function of the nature and seriousness of the observed toxicity and the dose at which it occurs in animals relative to the expected human intake of the substance. One of the unique and powerful approaches of animal testing is the administration of high amounts of a substance over a short time period. This allows the detection of effects with small groups of animals, the prediction of possible effects following prolonged human exposure, and the prediction of possible effects on particularly sensitive human subpopulations. Many animal studies focused on toxicity evaluate increasing dosages until signs of toxicity are seen. While the amount administered may not appear relevant to the non-scientist, organ toxicities at elevated intake in acute or subchronic studies can be indicative of toxicities that may develop at lower doses during chronic use of the ingredient and should therefore not be disregarded simply because the dose administered is higher than that taken by humans. On the other hand, in certain instances, data will indicate that positive animal studies conducted at high doses may falsely predict human outcomes because the excessive doses used in animals overwhelm normal detoxification mechanisms that would protect against toxicity at actual levels of human exposure.
While the assumption should be that any effects observed in animals are relevant to humans, under some circumstances known differences between humans and animals with respect to the pharmacokinetics and metabolism of a substance, interspecies differences in pharmacodynamics, or