ABSTRACT
The results of a 90-day rat feeding study with grain from MON 810 corn (YieldGard Cornborer -- YieldGard Cornborer is a registered trademark of Monsanto Technology, LLC) that is protected against feeding damage from corn and stalk boring lepidopteran insects are presented. Corn borer protection was accomplished through the introduction of cry1Ab coding sequences into the corn genome for in planta production of a bioactive form of Cry1Ab protein. Grain from MON 810 and its near-isogenic control was separately formulated into rodent diets at levels of 11% and 33% (w/w) by Purina Mills, Inc. (PMI). All diets were nutritionally balanced and conformed to PMI specifications for Certified LabDiet (PMI Certified LabDiet 5002 is a registered trademark of Purina Mills, Inc.) 5002. There were a total of 400 rats in the study divided into 10 groups of 20 rats/sex/group. The responses of rats fed diets containing MON 810 were compared to those of rats fed grain from conventional corn varieties. Overall health, body weight, food consumption, clinical pathology parameters (hematology, blood chemistry, urinalysis), organ weights, and gross and microscopic appearance of tissues were comparable between groups fed diets containing MON 810 and conventional corn varieties. This study complements extensive agronomic, compositional and farm animal feeding studies with MON 810 grain, confirming that it is as safe and nutritious as grain from existing commercial corn varieties.
Subject(s)
Plants, Genetically Modified/toxicity , Zea mays/toxicity , Animals , Blood Cell Count , Blood Chemical Analysis , Body Weight/drug effects , Diet , Eating/drug effects , Female , Insect Control , Male , Organ Size/drug effects , Rats , Sex CharacteristicsABSTRACT
The ability of frog embryo teratogenesis assay - Xenopus (FETAX) to identify the potential developmental toxicity of a group of diverse chemicals was evaluated by comparison with results from in vivo studies in rats. A total of 12 chemicals, three of which were shown to be teratogenic in vivo, four of which were embryolethal (but not teratogenic) in vivo, and five which did not produce any developmental toxicity in vivo in the rat were evaluated using FETAX. Results of the FETAX test with these 12 blind-coded compounds correctly predicted that three chemicals had strong teratogenic potential, four had low teratogenic hazard potential but were embryolethal, and five posed little if any developmental toxicity hazard. In addition, this study concluded that within a family of chemistry analogs could be ranked according to relative teratogenic hazard and that for the teratogenic compounds the types of malformations induced in Xenopus mimicked the abnormalities induced in vivo in rats. In summary, these results confirmed that the FETAX assay is predictive and can be useful in an integrated biological hazard assessment for the preliminary screening of chemicals. Teratogenesis Carcinog. Mutagen. 20:87-98, 2000.
Subject(s)
Abnormalities, Drug-Induced , Embryo, Nonmammalian/drug effects , Embryonic and Fetal Development/drug effects , Teratogens/toxicity , Toxicity Tests/methods , Xenopus laevis/embryology , Abnormalities, Drug-Induced/embryology , Abnormalities, Drug-Induced/mortality , Abnormalities, Drug-Induced/pathology , Animals , Embryo, Nonmammalian/abnormalities , Evaluation Studies as Topic , Female , Male , Maternal-Fetal Exchange , Predictive Value of Tests , Pregnancy , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Risk Assessment , Toxicity Tests/standardsABSTRACT
Dibutyl phenyl phosphate (DBPP) was administered to male and female Sprague-Dawley rats in their diets in separate subchronic (91-day) and two-generation reproduction studies. Dose levels of DBPP were 5, 50, and 250 mg/kg/day in both studies. In the reproduction study, cross-fostering was performed between some high-exposure and control litter offspring and dams following a second mating of F0 animals. Compared to control animals, body weights were consistently lower in high-exposure adult animals in both studies; this observation was less consistent in mid-exposure adult rats. High-exposure rats in the subchronic study had decreased erythrocyte counts and hematocrit and hemoglobin levels. They also had increased absolute and/or relative liver weights with concomitant decreased hepatocytic vacuolation and increased fatty accumulation. In the reproduction study, mating and fertility indices were comparable among the parental animals in both generations, but survivability among high-exposure pups reared by control dams appeared to be decreased. Urinary bladder histopathologic changes, consisting of mononuclear cell infiltration and transitional epithelial hyperplasia, were noted in mid- and high-exposure rats from both studies. The no observable adverse effect level in both of these studies was 5 mg/kg/day.
Subject(s)
Organophosphates/toxicity , Reproduction/drug effects , Animals , Blood Cell Count , Body Weight/drug effects , Diet , Female , Fertility/drug effects , Hematocrit , Kidney/drug effects , Liver/drug effects , Male , Organ Size/drug effects , Pregnancy , Rats , Rats, Inbred Strains , Sex FactorsABSTRACT
The benzidine congener 3,3'-dimethoxybenzidine (DMOB), and C.I. Direct Blue 15 (Blue 15), a prototypical compound of the DMOB-derived class of dyes, were evaluated in 13-week studies to characterize the toxicity and establish dose levels for subsequent chronic studies. Groups of 10 Fischer 344 rats of each sex were administered either DMOB, or Blue 15, at 1 of 5 concentrations in drinking water for 13 weeks. DMBO concentrations were 0, 0.017, 0.033, 0.063, 0.125, and 0.25% for males and females. For Blue 15, the concentrations were 0.063, 0.125, 0.25, 0.50, and 1.0% for females and 0, 0.125, 0.25, 0.50, 1.0, and 3.0% for male rats. Rats showed dose-related decreases in water consumption and weight gains. All DMOB-treated rats and their controls survived the 13-week treatment. There were 7 deaths in the 3% level of male rats treated with Blue 15. Liver and kidney weights were increased in rats treated with both compounds. Target organs for DMOB-treated rats were the kidney and thyroid. These lesions were characterized by chronic nephropathy, and increased pigment in the follicular cells of the thyroid. The kidney and liver were identified as target organs for Blue 15-treated rats. In the high-dose rats that died before termination of the study, renal effects were characterized by degeneration and focal necrosis of proximal tubular epithelial cells. Liver lesions in this group consisted of degeneration and necrosis of hepatocytes, fatty metamorphosis, and minimal megalocytosis. Mild chronic nephropathy was the principal histological effect in Blue 15-treated rats surviving to study termination.
Subject(s)
Azo Compounds/toxicity , Benzidines/toxicity , Coloring Agents/toxicity , Dianisidine/toxicity , Animals , Chemical Phenomena , Chemistry , Dose-Response Relationship, Drug , Drinking/drug effects , Female , Kidney/drug effects , Liver/drug effects , Male , Organ Size/drug effects , Rats , Rats, Inbred F344 , Thyroid Gland/drug effects , Weight Gain/drug effectsABSTRACT
Neoplasms of preputial gland and skin were obtained from Fischer 344 male rats on lifetime drinking water studies of the benzidine congener 3,3'-dimethoxybenzidine, C.I. Direct Blue 15 or C.I. Acid Red 114, bisazobiphenyl dyes derived from 3,3'-dimethoxybenzidine and 3,3'-dimethylbenzidine. Portions of these well differentiated neoplasms were implanted into the left mammary fat pad of Fischer 344 male recipients. The rate of growth, presence of local invasion and distant metastases, and morphologic features were observed following 4 serial transplantations. All implants appeared early, grew rapidly, and were histomorphologically similar to the original neoplasms. Metastases from transplants were observed with both preputial gland and skin tumor lines in serial passages. The transplantation results confirm the malignant nature of these neoplasms.
