Ingestion of Soil Contaminated with 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Alters Hepatic Enzyme Activities in Rats

Ingestion of Soil Contaminated with 2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD) Alters Hepatic Enzyme Activities in Rats. LUCIER, G.W., RUMBAUGH, R. C., MCCOY, Z., HASS, R., HARVAN, D., AND ALBRO,P. (1986). Fundam. Appl. Toxicol. 6, 36.4–371. Femalerats were treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)in either corn oil or contaminated soil from the Minker sitein Missouri. Eight doses ranging from 0.015 to 5 µg TCDD/kgwere used in the corn oil group; the range was 0.015 to 5.5TCDD/kg in the TCDD-contaminated soil group. Rats in a thirdgroup were given equal amounts of soil uncontaminated with TCDD.No acute toxicity or effects on body weight gain were observedat these doses. In general, equivalent doses of TCDD in cornoil or TCDD in soil produced similar increases in hepatic arylhydrocarbon hydroxylase activity (AHH) and UDP glucuronyltransferaseactivity although effects were slightly greater in the TCDD–cornoil groups. In the corn oil groups, the induction of AHH rangedfrom about 30-fold at the highest dose to twofold at the lowestdose studied. TCDD also caused an increase in cytochrome P-450concentration and a shift in spectral peak from 450 to 448 nm.There was no effect of TCDD on ethylmorphine N-demethylase,consistent with previous reports. Liver concentrations of TCDD(mean ± SD) in the 5-µg/kg groups were 40.8 ±6.3 ppb in the TCDD- corn oil group and 20.3 ± 12.9 ppbin the TCDD-contaminated soil group. Our results suggest thatthe bioavailability of TCDD in soil in rats is approximately50%. Therefore, ingestional exposure to TCDD-contaminated soilmay constitute a significant health hazard in view of its extremelyhigh toxicity and relatively high bioavailability.     

Benzene Hemoglobin Adducts in Mice and Rats: Characterization of Formation and Physiological Modeling

Benzene Hemoglobin Adducts in Mice and Rats: Characterizationof Formation and Physiological Modeling. SUN, J. D., MEDINSKY,M. A., BIRNBAUM, L. S., LUCIER, G., AND HENDERSON, R. F. (1990).Fundam. Appl. Toxicol 15, 468–475. Benzene is a myelotoxinand a human leukemogen. Humans are exposed to this compound,both occupationally and environmentally. This study was conductedto determine whether formation of benzene-derived adducts withblood hemoglobin (Hb) can be used as a biomarker of exposureto benzene. B6C3F₁ mice and F344/N rats were given 0.1 to 10,000µmol [¹⁴C]benzene/kg body wt, orally. Twenty-four hourslater, animals were euthanized, and globin was isolated fromblood samples. The globin was analyzed by liquid scintillationspectrometry for the presence of [¹⁴C]benzene-de-rived adducts.Hb adduct formation was linear with respect to dose for amountsof up to 500 µmol [¹⁴C]benzene/kg body wt, for both rodentspecies. Within this linear dose-response range, mice formedadducts from [¹⁴C]benzene approximately 3.5 times less efficiently[0.022 ± 0.010 (pmol adducts/mg globin)/(µmol/kgbody wt dose)] than did rats [0.076 ± 0.014 (pmol adducts)/µmol/kg body wt dose)]. Benzene-derived Hb adducts alsoaccumulated linearly when mice and rats were given up to threedaily doses of 500 µmol [¹⁴C]benzene/kg body wt. Thesedata were used to develop a physiological model for benzene-derivedHb adduct formation. Both first-order and saturable pathwaysfor adduct formation were incorporated. The results showed thatthe model simulated the levels of Hb adducts in both mice andrats after oral exposures to benzene and predicted the levelsof Hb adducts present after inhalation exposure. These studiessuggest that Hb adducts might be useful biomarkers for humanexposures to benzene.     

National Toxicology Program Studies: Principles of Dose Selection and Applications to Mechanistic Based Risk Assessment

A workshop entitled "NTP Studies: Principles of Dose Selectionand Applications to Mechanistic Based Risk Assessment" was heldat the 34th Annual Meeting of the Society of Toxicology in Baltimore,Maryland. The purpose of the workshop was to provide an overviewof factors currently considered important in the selection ofdoses for NTP studies, to describe some of the confounding factorsthat can result from the indiscriminate use of bioassay datain quantitative risk assessment, and to suggest ways in whichinformation from mechanistic studies or studies of biomarkersof exposure or effect might be used to better advantage in riskassessment.     

The dorsal vagal complex of the ferret: anatomical and immunohistochemical studies

To further the understanding of gastrointestinal function in this species, and in particular to advance our own work concerning central emetic pathways, the cytoarchitecture and the distribution of eight neurochemicals were studied in the ferret dorsal vagal complex (DVC; area postrema, nucleus of the solitary tract [nTS] and dorsal motor nucleus of the vagus). The cytoarchitectural features of this region in the ferret were similar to those seen in other species; however, the ferret possesses a particularly large and distinct subnucleus gelatinosus of the nTS. Dense calcitonin gene-related peptide-immunoreactivity was found in the gelatinous, interstitial and commissural subnuclei of the nTS, with lesser amounts in other regions of the DVC. Enkephalin-immunoreactivity of varying densities was found throughout the DVC. Moderate to dense galanin-immunoreactivity was observed throughout the DVC, with the exception of the subnucleus gelatinosus of the nTS, from which it was virtually absent. Dense neuropeptide Y-immunoreactivity was observed in the subnucleus gelatinosus and interstitial subnucleus, with moderate staining in other regions of the DVC. Neurotensin immunoreactivity was very sparse or absent. Immunoreactivity for serotonin was sparsely distributed throughout the DVC. Moderate somatostatin-immunoreactivity was observed over a large portion of the DVC, but was virtually absent from the gelatinosus and interstitial subnuclei. Substance P immunoreactivity was observed throughout the DVC and was particularly dense in the dorsal/dorsolateral subnucleus and the dorsal aspects of the medial and commissural subnuclei. In terms of its cytoarchitecture the DVC of the ferret is more similar to the cat than the rat, especially with regard to the area postrema and the subnucleus gelatinosus of the nTS. The distribution of neuroactive substances was largely similar to other species; however, differences were present particularly in patterns of immunoreactivity for enkephalin, serotonin, neuropeptide Y and somatostatin.