Risk assessments of polycyclic aromatic hydrocarbon mixtures are hindered by a lack of reliable information on the potency of both mixtures and their individual components. This paper examines methods for approximating the toxicity of polycyclic aromatic hydrocarbon (PAH) mixtures. PAHs were isolated from a coal tar and then separated by ring number using HPLC. Five fractions (A-E) were generated, each possessing a unique composition and expected potency. The toxicity of each fraction was measured in the Salmonella/mutagenicity assay and the Chick Embryo Screening Test (CHEST). Their abilities to induce ethoxyresorufin-O-deethylase and to inhibit gap junction intercellular communication in rat liver Clone 9 cells were also measured. In the Salmonella/mutagenicity assay, fractions were predicted to have potencies in the order C > D > E > B > A. Toxic equivalency factors (TEFs) for fractions A-E were in the order E > or = D > C > B > A. TEF values were 20,652, 20,929, 441, 306, and 74.1 micrograms of BaP equiv/g, respectively. A lack of agreement between assay-predicted potencies and chemical analysis-predicted potencies was observed with other assays and other methods of calculation. The results demonstrate the limitations of using a single method to predict the toxicity of a complex PAH mixture.
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 "aflatoxin binders." However, the efficacy and safety of these products have not been determined. A common zeolite that has been frequently added to animal feed is clinoptilolite. Our objectives in this study were twofold: (1) to utilize the pregnant rat as an in vivo model to compare the potential of HSCAS and clinoptilolite to prevent the developmental toxicity of aflatoxin B1 (AfB1), and (2) to determine the effect of these two sorbents on the metabolism and bioavailability of AfB1. Clay 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 clinoptilolite) alone and in combination with AfB1 were exposed to sorbents in the feed as well as by gavage. Untreated and AfB1 control animals were fed the basal diet without added sorbent. Between gestation 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 feed. Animals receiving AfB1 were dosed orally (between days 6 and 13) with AfB1 (2 mg/kg body wt) either alone or concomitantly with a similar quantity of the respective sorbent. Evaluations of toxicity were performed on day 20. These included: maternal (mortality, body weights, feed intake, and litter weights), developmental (embryonic resorptions and fetal body weights), and histological (maternal livers and kidneys). Sorbents alone were not toxic; AfB1 alone and with clinoptilolite resulted in significant maternal and developmental toxicity. Animals treated with HSCAS (plus AfB1) were comparable to controls. Importantly, clinoptilolite (plus AfB1) resulted in severe maternal liver lesions (more severe than AfB1 alone), suggesting that this zeolite may interact with dietary components that modulate aflatoxicosis. In metabolism studies, adult male Sprague-Dawley rats, maintained on diets containing 0.5% (w/w) HSCAS or clinoptilolite, were dosed orally with 2.0 mg AfB1/kg body wt. The concentration of the major urinary metabolite (AfM1) was considerably decreased in the presence of HSCAS. These results suggest that the mechanism of protection of AfB1-induced maternal and developmental toxicities in the rat may involve adsorption and reduction of AfB1 bioavailability in vivo. Importantly, this study demonstrates the potential for significant hidden risks associated with the inclusion of nonselective aflatoxin binders in feeds. Aflatoxin sorbents should be rigorously tested individually and thoroughly characterized in vivo, paying particular attention to their effectiveness and safety in sensitive animal models and their potential for deleterious interac...
Previous studies with low-pH montmorillonite (LPHM) clay exchanged with alkylammonium compounds showed that these organo clays were quite effective in sorbing the estrogenic mycotoxin zearalenone (ZEN) from aqueous solution. The potential toxicity of these types of clays, in particular hexadecyltrimethylammonium (HDTMA) LPHM, led to the investigation of the sorption efficacy of clay exchanged with a less toxic primary amine analog, hexadecylamine (HDA). Isothermal analysis studies showed that HDA LPHM was able to bind ZEN, but less effectively than HDTMA LPHM as evidenced by a significantly lower Freundlich K (63,900 vs. 845). The in vivo effectiveness of these two clays to bind ZEN was tested utilizing the mouse uterine weight bioassay. At a dietary inclusion level of 0.25%, the clays did not have a negative impact on overall animal health as measured by final body weight; however, they did not protect the animals from the estrogenic effects induced by 35 mg ZEN/kg in the feed (i.e., the uterine weights were not reduced in comparison to ZEN alone). In fact, the HDTMA LPHM group showed an increase in uterine weight that was more than the ZEN treatment group. When the animals were fed 0.5% clay, both exchanged clays (i.e., HDTMA LPHM and HDA LPHM) resulted in decreased body weight gain. The uterine weights of ZEN-fed animals (either alone or in combination with clays) were not significantly different from each other. In contrast, the uterine:body weight ratio showed a dramatic increase in the groups fed exchanged clay + ZEN compared to ZEN alone. These results suggest that alkylamine groups may assist the transport or uptake of ZEN and result in an enhanced toxicity from contaminated feed. The findings from this study clearly demonstrate the need for careful testing of all mycotoxin-binding agents before their inclusion in the diet.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.