PREVENTION OF MATERNAL AND DEVELOPMENTAL TOXICITY IN RATS VIA DIETARYINCLUSION OF COMMON AFLATOXIN SORBENTS - POTENTIAL FOR HIDDEN RISKS

In earlier work, we have reported that a phyllosilicate clay (HSCAS or NovaSil) can tightly and selectively bind the aflatoxins in vitro and in vivo. Since then, a variety of untested clay and zeolitic minerals have been added to poultry and livestock feeds as potential ''aflatox in binders.'' However, the efficacy and safety of these products have not been determined. A common zeolite that has been frequently added t o animal feed is clinoptilolite. Our objectives in this study were two fold: (1) to utilize the pregnant rat as an in vivo model to compare t he potential of HSCAS and clinoptilolite to prevent the developmental toxicity of aflatoxin B-2 (AfB(1)), and (2) to determine the effect of these two sorbents on the metabolism and bioavailability of AfB(1). C lay and zeolitic minerals (HSCAS or clinoptilolite) were added to the diet at a level of 0.5% (w/w) and fed to pregnant Sprague-Dawley rats throughout pregnancy (i.e., day 0 to 20). Treatment groups (HSCAS or c linoptilolite) alone and in combination with AfB(1) were exposed to so rbents in the feed as well as by gavage. Untreated and AfB(1) control animals were fed the basal diet without added sorbent. Between gestati on days 6 and 13, animals maintained on diets containing sorbent were gavaged with corn oil in combination with an amount of the respective sorbent equivalent to 0.5% of the estimated maximum daily intake of fe ed. Animals receiving AfB(1) were dosed orally (between days 6 and 13) with AfB(1) (2 mg/kg body wt) either alone or concomitantly with a si milar quantity of the respective sorbent. Evaluations of toxicity were performed on day 20. These included: maternal (mortality, body weight s, feed intake, and litter weights), developmental (embryonic resorpti ons and fetal body weights), and histological (maternal livers and kid neys). Sorbents alone were not toxic; AfB(1) alone and with clinoptilo lite resulted in significant maternal and developmental toxicity. Anim als treated with HSCAS (plus AfB(1)) were comparable to controls. Impo rtantly, clinoptilolite (plus AfB(1)) resulted in severe maternal live r lesions (more severe than AfB(1) alone), suggesting that this zeolit e may interact with dietary components that modulate aflatoxicosis. In metabolism studies, adult male Sprague-Dawley rats, maintained on die ts containing 0.5% (w/w) HSCAS or clinoptilolite, were dosed orally wi th 2.0 mg AfB(1)/kg body wt. The concentration of the major urinary me tabolite (AfM(1)) was considerably decreased in the presence of HSCAS. These results suggest that the mechanism of protection of AfB(1)-indu ced maternal and developmental toxicities in the rat may involve adsor ption and reduction of AfB(1) bioavailability in vivo. Importantly, th is study demonstrates the potential for significant hidden risks assoc iated with the inclusion of nonselective aflatoxin binders in feeds. A flatoxin sorbents should be rigorously tested individually and thoroug hly characterized in vivo, paying particular attention to their effect iveness and safety in sensitive animal models and their potential for deleterious interactions. (C) 1998 Society of Toxicology.