Effects in Animals

The effects of drugs in animals are usually concentration dependent and are also often animal species and site-of-action dependent thus the compounds may be present naturally in diets at low levels and produce no obvious adverse effects, either on the animal, gut microflora, meat, milk or eggs. The main purpose of the use of drugs in animal feeds is to improve the animal health and welfare and often to improve growth at minimum cost to the producer.In the case of naturally produced compounds that may occur in the feedstuff s of animals, these compounds may impair animal health and performance as well as cause im- 

Compounds in animal diets can exert their effects in the gastrointestinal tract or after absorption through the gut epithelial tissue into the bloodstream, or both. On some occasions the administered compounds may be applied topically (Table 1). 

A wide variety of animal species are subjected to the administration of drugs during their lifetime.The various animal species can encounter drugs and other dietary additives by different routes and this is dependent on the environment in which they are kept. Intensively reared animals tend to have considerable consistency in the components of their diets and thus are much less likely to encounter the range of naturally produced compounds that extensively produced animals encounter. The desire for less expensive dietary constituents and increased efficiency of use has induced feed manufacturers and producers to add enzyme supplements to diets of most farmed animals to reduce the negative effects of indigestible dietary carbohydrates, refactory proteins and unavailable minerals such as phosphorus. This use of dietary additives to improve nutrient utilization and environmental consequences of feeding animals intensively has been the subject of intense research activity in the last five years. The 

Classen and M. R. Bedford, in Recent Advances in Animal Nutrition, ed. W. Haresign and D.J.A. Cole, Butterworth-Heinemann, Oxford, 1991, p. 95. 

Drugs and Dietary Additives, Their Use in Animal Production 

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The term nootropic has been used to describe a class of compounds defined by the abibty of its members to facibtate learning (36). The compounds are most effective in animals that have had their cognitive abihties compromised in some way. The molecular mechanism undedying the cognitive-enhancing... 

There appear also to be toxic effects. In animals, nitrous oxide has been shown to inactivate methionine synthetase which prevents the conversion of deoxyuridine to thymidine and thus has the potential for inducing megaloblastic anemia, leukopenia, and teratogenicity (44—46). A variety of epidemiologic surveys suggest positive correlations between exposure to nitrous oxide and spontaneous abortion in dental assistants (47). 

Value is toxic dose low. TD q, the lowest dose of a substance introduced by any route other than inhalation, over any given period of time to which humans or animals have been exposed and reported to produce any nonsignificant toxic effect in humans or to produce nonsignificant tiimorigenic or reproductive effects in animals or humans. 

Effects in Animals. The LD ia rats for all light chlorophenols, irrespective of the administration route, ties between 130 and 4000 mg/kg body weight. The toxicity of these compounds ia order of increasing strength is tetrachlorophenols > monochloropheno1 s > dichlorophenols > trichlorophenols when the chlorophenol is administered either orally or by subcutaneous iajection. 

Within the constraints of this article it is impossible to be comprehensive in the coverage of the subject matter, in terms of the chemicals involved and in the widely varying practices and areas of the world in which the title compounds are ingested by farmed animals. This account is, however, intended to give an overview, citing some relevant examples, of the beneficial and adverse effects, in animals and on the environment, of man-made compounds and naturally produced compounds in extensive and commercial production systems. 

In the aitways, inhibition of PDE4 is much more antiinflammatory than bronchodilatory. Although effective in animal experiments, the neuronal and gastric side effects of PDE4-inhibitors have so far impeded their use in humans. Two new orally active PDE4-inhibitors (roflumilast, cilomilast) have shown some effectiveness in advanced clinical trials, but have not yet been approved. 

No studies were located regarding hepatic effects in animals atter inhalation exposure to methyl parathion. 

In summary, based on these studies, the evidence for endosulfan-induced adverse developmental effects in animals is inconclusive. The highest NOAEL value and all reliable LOAEL values for developmental effects in rats and rabbits for the acute- and intermediate-duration categories are recorded in Table 2-2 and plotted in Figure 2-2. 

No studies were located regarding immunological or lymphoreticular effects in animals following dermal exposure to trichloroethylene. 

Assessment of whether a chemical has the potential to cause adverse effects in humans arises usually from direct observation of an effect in animals or humans, such as the acute poisoning episodes that have occurred when potatoes contain high levels of glycoalkaloids. Epidemiological studies have also been used to infer a possible relationship between intake of a particular type of food, or constituent of that food, and the potential to cause an adverse effect. Such observations led to the characterisation of the aflatoxins as human carcinogens. However, natural toxic substances that occur in plant foods have often been identified through observations in animals, particularly farm animals. It was observations of adverse effects in farm animals that led to the further characterisation of the phytoestrogens and the mycotoxins. In other instances, the concern arises from the chemical similarity to other known toxins. 

Phencyclidine (1 -[1-phenylcyclohexyl]pi peridine HC1 PCP) and its active derivatives produce unique behavioral effects in animals and psychotomimetic effects in humans. Drugs of this class have been demonstrated to bind saturably, reversibly, and with high affinity to specific binding sites in brain (Hampton et al. 1982 Quirion et al. 1981 Sircar and Zukin 1983 Vincent et al. 1979 Zukin and Zukin 1979). These sites have been shown to exhibit a characteristic heterogeneous regional distribution pattern (Quirion et al. 1981 Sircar et al., submitted for publication Zukin and Zukin 1979) distinct from that of any other receptor type. 

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