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ABSTRACT: A pilot study using female cynomolgus (Macaca fascicularis) and female rhesus (Macaca mulatta) monkeys was conducted to study the effects of chronic ingestion of polychlorinated biphenyls (PCBs). Four control and four treated monkeys of each species received an apple juice-gelatin mixture containing 0 and 280 micrograms Aroclor 1254/kg body weight/day, respectively, 5 days/wk. The cynomolgus monkeys, which were mature monkeys with a poor breeding history, were treated for approximately 55 wk, while the rhesus monkeys, which were just attaining sexual maturity, were treated for approximately 120 wk. After 38 wk on test, the treated and control rhesus monkeys were mated with untreated males. The clinical signs resulting from the Aroclor 1254 ingestion were similar for both species, and the time of onset after initiation of treatment was not appreciably different between the two species. Several treatment and interspecies differences were found with regard to the haematological and serum biochemistry parameters monitored, but age differences between the two species may have contributed to these findings. Periodic analysis of adipose tissue, blood and faecal specimens for PCBs suggested that the rhesus monkey retained more of the ingested PCB than did the cynomolgus monkey. Following mating, all of the treated rhesus monkeys aborted within 30-60 days after becoming pregnant, while all of the control monkeys had viable offspring.
Food and Chemical Toxicology 01/1991; 28(12):847-57. · 3.00 Impact Factor
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ABSTRACT: The result of feeding Aroclor 1254 to female Rhesus monkeys at doses of 0, 5, 20, 40 and 80 micrograms/kg body weight/day for a period of 37 months was measured in terms of polychlorinated biphenyl (PCB) levels in blood, adipose tissue, and feces. PCB concentrations in whole blood increased more rapidly during the first 10 months of the study than in the remaining 27 months for all dose groups. On a blood-lipid basis, however, another rapid increase in PCB levels was observed after 27 months of dosing, which could not be explained on the basis of an overall decrease in blood-lipid levels. Concentrations in adipose tissue and adipose fat increased continuously during the 37 months of dosing. These observations were reflected in the ratio profiles of PCB levels in blood/PCB levels in adipose tissue, which remained relatively static between the 2nd and 27th month of continuous feeding. Expressing the data in terms of relative concentrations (concentration/dose) suggests that bio-accumulation or retention of PCBs may be dose-dependent, particularly for adipose tissue, with the higher relative concentrations of the lowest dose group significantly (p less than 0.001) different from all other dose groups. Similarly, the limited feces data available suggests a dose-dependent PCB absorption. The distribution of PCB peaks in the gas chromatographic elution pattern of all analyzed substrates showed considerable deviation from that of administered Aroclor 1254. Only minor changes in the percent distribution pattern were observed between dose groups.
Archives of Environmental Contamination and Toxicology 12/1989; 18(6):858-65. · 1.93 Impact Factor
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Bulletin of Environmental Contamination and Toxicology 12/1989; 43(5):667-9. · 1.02 Impact Factor
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Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 10/1989; 221(2):69-132. · 2.85 Impact Factor
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ABSTRACT: The effects of PCB (Aroclor 1254) on the immune system of adult female rhesus monkeys were investigated in a chronic study wherein five groups of monkeys (16/group) were administered (orally) PCB at levels of 0.0, 5.0, 20.0, 40.0 or 80.0 micrograms/kg body wt daily. Tests for immunotoxicity were initiated at 23 months of exposure to PCB, at which time the monkeys had achieved an apparent pharmacokinetic steady state based on the PCB concentration in fat and/or blood. A statistically significant (P less than 0.05) dose response reduction in antibody levels (IgG and IgM) to sheep red blood cells (SRBC) was observed following i.v. administration of three immunizing doses of SRBC at weekly intervals. A statistically significant decrease in the percent TH and an increase in the percent and absolute TS lymphocyte levels was found in the 80 micrograms/kg body wt group compared to the control. The TH/TS ratio was also significantly lower in the 80 micrograms/kg body wt group compared to the control. Other parameters investigated including percent of B-lymphocytes and total T-lymphocytes, total serum immunoglobulin levels (IgG, IgM and IgA), other serum proteins, glucocorticosteroid levels and lymphocyte transformation results following stimulation with the mitogens PHA-P and Con A were not affected significantly by PCB treatment. Additional immunologic parameters are currently being investigated to further elucidate the mechanism by which PCB induces immunotoxicity.
International Journal of Immunopharmacology 02/1989; 11(2):199-206.
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ABSTRACT: Two studies were conducted with weanling male rodents in an attempt to ascertain more precisely the toxic effects of deoxynivalenol (DON). In a feeding study of approximately 18-wk duration, groups of 90 Swiss-Webster derived mice and 50 Sprague-Dawley rats were fed a commercial chow (118 ppb DON), and groups of 80 mice and 50 rats were fed either an 'uncontaminated' diet (53 ppb DON) or a contaminated diet (6250 ppb DON), both based on wheat. A 5-wk gavage study was also performed, in which 24 litters of 5 Swiss-Webster-derived mice were divided among the following groups: an untreated control group, a solvent control group, and three treated groups receiving 0.75, 2.5 or 7.5 mg DON/kg body weight. While there were interim kills in the feeding study, most of the animals given 7.5 or 2.5 mg/kg in the gavage study died during the test period. Effects on body weight and haematological parameters in both studies indicate that DON elicited some degree of toxicity at all levels tested. The histopathological findings from the gavage study suggest that DON had effects on the immune system as well as being a gastro-intestinal irritant.
Food and Chemical Toxicology 10/1986; 24(9):935-41. · 3.00 Impact Factor
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ABSTRACT: Groups of 25 male and 25 female Sprague-Dawley rats were fed diets containing 0, 0.25, 0.5, or 1.0 mg of deoxynivalenol (DON)/kg body wt for approximately 9 weeks. Each animal's body weight and feed consumption were measured weekly. Upon termination of the study, each animal's body, heart, liver, spleen, thymus, and kidneys were weighted. A hematological assessment and a 16-parameter serum evaluation were conducted and 8 animals from each group were randomly selected to receive tritiated thymidine iv to assess mitotic activity in the esophagus, jejunum, and spleen. A statistically significant, dose-related decrease in body weight gain was observed for all treated females, but only the males dosed at 1.0 mg/kg were found to have a treatment-related weight gain suppression. The reduced body weight was attributed to a reduced feed consumption. Reductions that were observed in absolute organ weights, were not apparent after adjusting for body weight suppression. No dose-related hematological findings were found. Serum chemistry changes included increased concentrations of chloride and decreased concentrations of CO2 and albumin, but only in the females. No histopathological lesions were attributed to DON treatment, but significant decreases in thymidine labeling occurred in the spleens and jejunums from the males dosed at 1.0 mg/kg.
Fundamental and Applied Toxicology 06/1986; 6(4):691-6.
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ABSTRACT: The toxicological effects of analytical grade hexachlorobenzene (HCB) were examined in a two-generation feeding study in which 40 male and 40 female weanling Sprague-Dawley rats, except where noted, were fed diets containing 0.0 (64 males, 64 females), 0.32, 1.6, 8.0 or 40.0 (66 males, 66 females) ppm HCB. After 3 months on test, the F0 rats were bred and 50 pups (F1) of each sex were randomly selected from every group. At weaning the F0 animals were killed, and the F1 animals were fed their parents' diet for the remainder of their lifetimes (130 weeks). There were no treatment-related effects on growth, feed consumption, haematological parameters or survival in either generation. Increased heart and liver weights were found in the F0 generation males fed 8.0 and 40 ppm HCB. HCB had no effect on fertility, but did significantly reduce pup viability in the 40.0-ppm group. Histopathological changes in the F1 generation included significant linear trends for the incidence of parathyroid adenomas and phaeochromocytomas in both sexes, neoplastic liver nodules in females, centrolobular basophilic chromogenesis of the liver in both sexes, peliosis of the liver in females, peribiliary lymphocytosis of the liver in males and chronic nephrosis of the kidney in males.
IARC scientific publications 02/1986;
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ABSTRACT: Aroclor 1254, at a dose level of 280 micrograms/kg body weight equivalent to 200 micrograms/kg/day, was given 5 days per week to rhesus monkeys over a 27 to 28 month period. Terminal clinical signs of varying severity included fingernail detachment, exuberant nail beds, weight loss, stomatitis and normocytic anemia. At necropsy the bone marrow was hypocellular with increased M:E ratio and cytoplasmic vacuoles in erythroid precursor cells. Histopathologic lesions included dilatation of the tarsal gland ducts, atrophy or absence of splenic and lymph node germinal centers, bone marrow depletion, gingival erosion and ulceration, moderate mucinous hypertrophic gastropathy with cystic dilatation of occasional gastric glands, hepatocellular enlargement and necrosis, hypertrophy of biliary duct epithelium, hyperplasia of biliary ducts, hypertrophy of the gall bladder epithelium, and an equivocal increase in the number of lysosomes in thyroid follicular epithelial cells. PCB tissue concentrations were lowest in brain and highest in blood. The results suggest that severe potentially fatal PCB toxicity can develop in rhesus monkeys following ingestion of Aroclor 1254 at 200 micrograms/kg/day for a period of 27 months or longer.
Toxicologic Pathology 02/1986; 14(1):1-10. · 1.91 Impact Factor
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ABSTRACT: The toxicological effects of analytical-grade hexachlorobenzene (HCB) were examined in two chronic studies. Study I was an in utero exposure carcinogenicity feeding experiment in which Sprague-Dawley rats, in groups of 40 males and 40 females except where noted, were fed from weaning on diets containing 0.0 (64 M/64 F), 0.32, 1.6, 8.0 or 40.0 (66 M/66 F) ppm HCB. After 3 months on test, the F0 rats were bred and 50 pups (F1) of each sex were randomly selected from every group. From weaning, when the F0 animals were killed, the F1 animals were fed their parents' diet for the rest of their life (130 wk). There were no treatment-related effects on growth, feed consumption, haematological parameters or survival in either generation. Increased heart and liver weights were found in the 8.0 and 40 ppm F0 males. HCB had no effect on fertility but pup viability was significantly reduced in the 40 ppm group. Histopathological changes in the F1 generation included significant linear trends in the incidence of parathyroid adenomas and phaeochromocytomas in both sexes, neoplastic liver nodules in females, centrilobular basophilic chromogenesis of the liver in both sexes, peliosis of the liver in females, peribiliary lymphocytosis of the liver in males and chronic nephrosis of the kidney in males. In Study II, the toxicological effects of HCB were examined as a consequence of varying the dietary levels of vitamin A. In this single generation lifetime (119 wk) feeding study, groups of 50 weanling Sprague-Dawley male rats were randomly assigned to each of the following dietary groups: control, control + 40 ppm HCB, 1/10 the vitamin A content of the control diet, 1/10 vitamin A + 40 ppm HCB, 10 times the vitamin A content of the control diet and 10 times vitamin A + 40 ppm HCB. After 25 and 49 wk on test, five animals from each group were killed and subjected to haematological and histological examinations. All other aspects of evaluation were similar to those for the F1 generation in Study I. No consistent differences were observed in the haematological parameters and there were no significant differences in the incidence of pathological lesions between the test groups. The animals in the 1/10 vitamin A groups, with or without HCB, had significantly lower body weights and poorer survival than did their corresponding control (normal vitamin A) groups.
Food and Chemical Toxicology 10/1985; 23(9):779-93. · 3.00 Impact Factor
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ABSTRACT: The effects of vomitoxin (deoxynivalenol; DON) on the immune system were studied in groups of weanling male Swiss Webster mice administered by gavage 0.75, 2.5, and 7.5 mg of vomitoxin per kg body weight. Untreated controls and solvent controls (propylene glycol, ethanol, and distilled water in a ratio of 4:1:5) were also included in this study. Serum antibody (IgM) levels to sheep red blood cells (SRBC) were significantly reduced in the treatment groups compared to the control groups. Plaque-forming cell (PFC) numbers were also lower in the treated groups compared to the control groups. Furthermore, vomitoxin at a dose of 0.75 mg/kg resulted in a significant increase in the albumin, albumin/globulin ratio and a decrease in the alpha-2 globulin fraction compared to the control groups. Administration of 7.5 mg/kg of vomitoxin resulted in deaths, due to toxicity, in all animals of this group within 3 weeks. These preliminary findings are indicative of a potential effect of vomitoxin on the immune system which could have serious implications to man.
Toxicology Letters 11/1984; 23(1):17-24. · 3.23 Impact Factor
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ABSTRACT: Weanling male and female mice (F0) were fed daily diets containing 4-deoxynivalenol (DON) at concentrations that resulted in a dose of 0 or 2.0 mg/kg body wt in Experiment I and 0, 0.375, 0.75, or 1.5 mg/kg body wt in Experiment II. The test diets were continuously fed to the F0 parents and their progeny for the entire duration of these two experiments, which were similar in design. After 30 days of dietary feeding, the mice were allowed to mate within experimental groups for a maximum of three 5-day trials. Females found to have mated successfully were allowed to litter normally. The F1a progeny from 10 dams of each control and 1.5-mg DON/kg groups were cross-fostered at birth, whereas all of the remaining F1a progeny were reared by their natural dams. The progeny were examined until 21 days of age and discarded. The F0 mice were rebred. The females bred to produce the F1b litters were killed on Day 19 of gestation and their fetuses were examined for gross, visceral, and skeletal malformations. Reductions were observed in feed and water intakes and body weight of F0 male and female mice, the number of live pups and postnatal survivors, postnatal body weight of F1a progeny, number of live fetuses, and mean fetal weight of F1b fetuses. No adverse effects on fertility of F0 male and female mice and no major malformations in F1b were found. Cross-fostering offspring between control dams and 1.5-mg DON/kg-treated dams revealed that both postnatal survival and body weight were adversely affected by prenatal exposure as well as by a combined pre- and postnatal exposure. Male and female Sprague-Dawley rats were fed diets containing DON so as to deliver daily doses of 0.25, 0.5, or 1.0 mg/kg body wt. After 6 weeks of feeding, the rats were bred within groups and the males were then discarded. The mated females, maintained on their respective diets for the entire period of pregnancy, were killed on the last day of pregnancy and fetuses evaluated for effects on prenatal development. Except for dilation of renal pelvis and urinary bladder, the significance of which remains undetermined, no other adverse effect was observed.
Toxicology and Applied Pharmacology 08/1984; 74(3):345-56. · 4.45 Impact Factor
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ABSTRACT: Groups of 50 male and 50 female Sprague-Dawley rats were fed diets containing 0, 75, 100, or 150 ppm ethylenethiourea (ETU) for 7 weeks, at which time subgroups of 10 animals from each group were killed. Subsequent subgroups of 10, 10, and 20 animals were killed after an additional 2, 3, and 4 weeks, respectively, on the control diet in order to examine whether the toxicological effects induced by ETU were reversible. In both sexes, the mean body weight and feed consumption were significantly decreased in all treated groups, while the mean thyroid weight (absolute as well as relative to both body and brain weight) appeared to increase linearly with dose. Mean T4 blood levels in animals fed 150 ppm ETU were significantly below those in controls. The magnitude of the changes in body weight, thyroid weight, and T4 blood levels observed during the first 7 weeks of the study decreased after ETU was removed from the diet. The statistical procedures developed and applied here may be useful in other experiments designed to assess the reversibility of other toxicological endpoints.
Toxicology and Applied Pharmacology 03/1983; 67(2):264-73. · 4.45 Impact Factor
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Toxicology and Applied Pharmacology 02/1980; 52(1):113-52. · 4.45 Impact Factor
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Food and Cosmetics Toxicology 01/1980; 17(6):661-75.
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Toxicology and Applied Pharmacology 01/1980; 51(3):455-63. · 4.45 Impact Factor
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Progress in experimental tumor research. Fortschritte der experimentellen Tumorforschung. Progrès de la recherche expérimentale des tumeurs 02/1979; 24:222-34. · 0.42 Impact Factor
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Food and Cosmetics Toxicology 11/1978; 16(5):479-84.
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Food and Cosmetics Toxicology 09/1978; 16(4):369-71.
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Science 08/1977; 197(4301):320. · 31.20 Impact Factor
