Nutritional animal studies

Animal studies indicate that nutritional deficiencies in a number of essential elements (e.g., calcium, iron, zinc, copper, phosphorus) may impact the toxicokinetic and toxicological behavior of lead (ATSDR 1993 Chaney et al. 1989). In infants and children, lead retention has been shown to be inversely correlated with calcium intake (Johnson and Tenuta 1979 Sorrell et al. 1977 Ziegler et al. 1978). Zinc has been shown to have a protective effect against lead toxicity in a number of animal species (Goyer 1986 Haeger-Aronsen et al. 1976 Brewer et al. 1985 Cerklewski and Forbes 1976). 

Numerous physiological and environmental factors such as age, stress, nutritional deficiency, and infections may affect the immune system (Sullivan, 1989). Thus, adverse findings in animal studies may reflect these indirect immunotoxic effects rather than the direct immunotoxic potential of a chemical or drug. Indirect immunotoxic effects may be assessed through histopathologic evaluations of endocrine organs such as the adrenals and pituitary. 

The gold standard for human studies is called the randomized, controlled clinical trial. Such trials are close to experimental animal studies, but for obvious ethical reasons, they cannot be conducted to identify toxicity. They are, instead, designed to determine whether certain pharmaceutical or nutritional regimens, for example, reduce the risks of disease. They may provide information about adverse side effects, but they are not designed for studying toxicity. 

In animal studies of cellulose derivatives, the only consistent effect of very high doses in the feed appears to be a reduction in the nutritional value of the feed, which manifests itself as a decrease in body weight gain or an increase in food consumption. Doses up to 5000mg/kg/body weight/day or 10% in the diet, have been found to be nontoxic. 

Nutritional status can also influence the toxic potency of carbon tetrachloride. Animal studies have clearly demonstrated that brief fasting or consumption of diets low in antioxidants (vitamin E, selenium, methionine) can lead to increased carbon tetrachloride hepatotoxicity. The same may be true for humans, although this is not known for certain. Another aspect of nutritional status affecting carbon tetrachloride toxicity is hepatic energy status. Hepatic ATP levels might influence the ultimate outcome of toxicity (low levels may inhibit recovery mechanisms). 

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