Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As little information is available on the adverse effects of polychlorinated biphenyls (PCBs) on the reproductive system of the male rat, the current study was conducted to evaluate the effects of subchronic administration of the PCB mixture Aroclor 1254 on testicular gamete production and endocrine function. The thyroid hormone thyroxine (T4), which is critical for reproduction and development, was also measured because of the well-documented effects of PCBs on this hormone. Weanling (31-day-old) male Fischer rats were administered 0, 0.1, 1, 10, or 25 mg/kg/day Aroclor 1254 by gavage for 5, 10, or 15 weeks and necropsied. The hormones testosterone (T) and thyroxine were measured in the serum, and body weight and weights of the liver, kidney, testes, seminal vesicle plus coagulating gland, cauda epididymides, and pituitary were taken. At 10 and 15 weeks, testicular interstitial fluid (IF) was collected and T concentration in the IF was measured. Sperm motility was measured from a caudal sperm sample and sperm numbers in the testis and cauda epididymis were determined. In addition, tissues were examined microscopically for histopathological alterations. In the high-dose group, body, seminal vesicle, cauda epididymal, and pituitary weights were depressed at 10 and 15 weeks and cauda epididymal sperm numbers were reduced after 15 weeks of dosing. In contrast, testes weights, testicular sperm numbers, sperm motility, and serum and testicular testosterone levels were unaffected, even in the highest dose group (25 mg/kg/day). Aroclor 1254 administration produced histological alterations in the liver and kidney at doses of 1.0 mg/kg/day and above.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reproductive and thyroid effects of low-level polychlorinated biphenyl (Aroclor 1254) exposure. 850 2

Fasting and thyroid hormone have been reported to modulate the beta-adrenergic pathway of lipolysis in rat, but their effects on the alpha 2-adrenergic response are not well known. The purpose of the present study was to investigate this point. Male Wistar rats, 3 weeks old, were thyroidectomized surgically, kept for 1 month at 25 degrees C and then fasted or not fasted for 3 days with or without daily intraperitoneal injection of 3,5,3'-tri-iodo-L-thyronine (T3; 4.6 nmol/100 g body weight). Age-matched, sham-operated, fed and fasted euthyroid rats were used as controls. The experiments were carried out using isolated epididymal adipocytes. The alpha 2-adrenergic agonist UK 14304 (UK) inhibited the stimulated lipolysis more in fed than in fasted euthyroid rats whereas it had no effect in hypothyroid or T3-treated hypothyroid rats. The alpha 2-adrenergic antagonist idazoxan reversed the antilipolytic effect of UK more in fasted than in fed euthyroid rats. The alpha 2-adrenergic antagonist RX 821002 (RX) did so, but at lower concentrations than those of idazoxan. Idazoxan slightly increased the glycerol release in hypothyroid and especially T3-treated hypothyroid rats. RX had practically no effect on the production of glycerol in these animals. The findings suggest that (a) fasting and probably hypothyroidism decrease the alpha 2-adrenergic response in adipocytes from rats, (b) T3 treatment of hypothyroid rats has no effect on the alpha 2 response, and (c) thyroid hormone does not directly modulate the alpha 2-adrenergic response in rat adipocytes.
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PMID:Influence of prolonged fasting and thyroid hormone on the alpha 2-adrenergic response in isolated epididymal adipocytes of Wistar rats. 911 19

The effect of fasting on hormonal and metabolic variables was evaluated in normal rats and in rats with obesity induced by neonatal treatment with monosodium glutamate (MSG). The hyperinsulinemia of the fed obese rats was reversed by fasting. Plasma corticosterone was also high in the fed obese and decreased to levels similar to fed controls, while it increased in the latter group during fasting. In contrast, thyroid hormone levels decreased in controls but increased in the obese rats in response to fasting. The fed obese group had lower carcass protein and higher carcass lipid contents than controls. In response to fasting, the decrements of the initial amount of both protein and fat were lower in MSG than in controls. Fasting induced a sustained increase in plasma free fatty acids only in the obese rats, although a single 100 mumol.l-1 dose of norepinephrine stimulated in vitro glycerol release more pronouncedly in epididymal adipocytes from control than obese rats. The results indicate that MSG-obese rats were able to mobilize fat stores during prolonged fasting. The high availability of lipid fuels and the sharp and sustained decrease in circulating corticosterone in the MSG group were probably important in diminishing body protein consumption during fasting.
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PMID:Hormonal and metabolic adaptations to fasting in monosodium glutamate-obese rats. 928 91

The toxicity of 3,3',4,4'-tetrachloroazobenzene (TCAB) was evaluated in 13-week gavage studies in male and female F344/N rats and B6C3F1 mice. In addition to histopathology, evaluations included clinical chemistry, hematology, thyroid hormone analyses, and reproductive parameters. Groups of 10 rats and 10 mice of each sex were exposed to TCAB at dose levels of 0, 0.1, 1, 3, 10, or 30 mg/kg for 5 days a week for 13 weeks. In the rat studies, the major effects for both males and females included a 10% decrease in terminal body weight at 30 mg/kg/day, an increase in hematopoietic cell proliferation in the spleen at 10 and 30 mg/kg/day, and a responsive anemia at 10 and 30 mg/kg/day. A 15 to 30% decrease in platelet counts and a 20 to 40% decrease in thymus weights was observed at 10 and 30 mg/kg/day. An increase in liver weight up to 15% was found at 3 mg/kg/day and higher doses in males and at 10 and 30 mg/kg/day in females, respectively. An increase in spleen weights up to 15% was observed at 10 and 30 mg/kg/day in males and at 30 mg/kg/day in females. A marked decrease in circulating total thyroxine (TT4) was found in both males and females at all dose levels tested. TT4 could hardly be detected at 10 and 30 mg TCAB/kg/day. In addition, hyperplasia of the forestomach was increased at 3 mg/kg/day and higher doses in males and at 30 mg/kg/day in females. In the mouse studies, an increase in liver and spleen weight was observed up to approximately 25% in both males and females at 10 and 30 mg/kg/day. Hyperplasia of the forestomach was observed at 1 mg/kg/day and higher doses in both males and females. In males, a 30% decrease in thymus weights at 30 mg/kg/day and a 60% decrease in epididymal sperm density at 3 and 30 mg/kg/day was observed. Also in males, centrilobular hypertrophy of hepatocytes and an increase in hematopoietic cell proliferation in the spleen was observed at 3 mg/kg/day and higher doses. Based on the current study and information in the literature, TCAB has dioxin-like properties. Comparison of the effects of TCAB in the present study and in the literature to those with 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) indicates that TCAB is from two to six orders of magnitude less potent than TCDD depending on the end point.
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PMID:Toxicity of 3,3',4,4'-tetrachloroazobenzene in rats and mice. 1019 80

The effect of centrally administered rat leptin on selection of 5 and 30% protein diets was investigated in male Sprague-Dawley rats with indwelling i.c.v. cannulas. Leptin (0 vs 2.5 microg/day) was administered for 4 consecutive days, followed by an 8-day withdrawal period. Total intake was reduced to approximately 50% of that in the vehicle injected group during each day following leptin administration. Intake of both the 5 and 30% diets was reduced. Vehicle-treated rats selected a 13-15% CP diet. Diet selection in leptin-treated rats was not different during the first day, but on Days 2-4, leptin-treated rats selected a 10% CP diet. Intake began to normalize within 24-48 h after the last treatment, and was not different by Day 3 of the withdrawal period. Body weight was reduced by leptin treatment, and despite the normalization of food intake, did not recover during the withdrawal period. Rats were sacrificed at the end of the 8-day withdrawal period. Despite the reduction in body and carcass weights, liver, kidney, heart, and soleus muscle weights were not different between control and leptin-treated groups when expressed on an absolute or relative basis. However, epididymal and retroperitoneal fat pad weights were still reduced 56 and 78%, respectively, in rats that had been previously treated with leptin for 4 days and then not treated for 8 days. In addition, circulating T3 levels remained elevated in rats that had been treated with leptin. Centrally administered leptin has little effect on muscle mass, but had potent effects on intake of nonobese rats and a sustained effect on adipose tissue mass, thyroid hormone status, and body weight after withdrawal. Results from rats selecting between diets varying in protein content suggest that leptin may cause avoidance of protein.
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PMID:Effects of intracerebroventricularly administered leptin on protein selection in the rat. 1035 46

The physiological consequences and mechanism(s) for thyroid hormone-induced alterations in serum leptin are not known. To address this, leptin expression in rats was evaluated in relationship to food intake, fat mass, and body temperature in rats with pharmacologically altered thyroid status. Total body weight, food intake, and temperature were decreased in hypothyroid rats. Fat weight was decreased in both chronically hypothyroid and hyperthyroid rats (n = 6/group). Serum leptin was linearly correlated with fat weight, epididymal and retroperitoneal fat leptin mRNA concentration, but not total body weight. Serum leptin was decreased in the chronically hyperthyroid rats. When fat weight was used as a covariant, serum leptin was not different between the three groups. Epididymal fat leptin mRNA was higher in euthyroid (n = 7) than in hypothyroid and hyperthyroid rats. Retroperitoneal fat leptin mRNA was not affected by thyroid status. A positive linear relationship between food intake and free triiodothyronine (FT3) index was observed, but not between food intake and serum leptin alone. In a time course study, serum leptin, epididymal fat leptin mRNA content, and fat weight did not change within 24 hours of high-dose triiodothyronine (T3) (n = 6/group), but both temperature and epididymal fat S14 mRNA content rapidly increased. These findings demonstrate that thyroid state influences circulating leptin levels, but primarily does so indirectly through the regulation of fat mass. Leptin does not influence core body temperature across thyroidal state. Finally, thyroid state is more important to regulate food intake, through an as yet undefined mechanism, than are thyroid state-associated changes in serum leptin.
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PMID:The effect of thyroid hormone on size of fat depots accounts for most of the changes in leptin mRNA and serum levels in the rat. 1036 83

To determine whether resistance to insulin or to thyroid hormones rather than an inherent defect in enzyme activity expression account for the age-related changes in lipogenic enzymes, the activities of malic enzymes (ME), fatty acid synthase (FAS), glucose-6-phosphate dehydrogenase (G-6PD) and 6-phosphogluconate dehydrogenase (6-PGD) were assayed in hepatic, retroperitoneal fat and epididymal fat cytosol of male Fischer 344 rats at 3.5, 12 and 25 months of age. The rats were maintained on either regular rat chow with 62% of calories as complex carbohydrates or were given either high glucose or fructose diet with 65.7% of calories provided by glucose or fructose respectively. Additional groups of young and aged rats were treated with L-triiodothyronine (T3) (15 microg/100 g body weight) for 10 days. Treatment with T3 resulted in higher levels of hepatic ME activity regardless of the diet consumed or the age of the rats. T3 had no consistent effect on FAS, G-6PD or 6-PGD activities. ME response to T3 in young rats was significantly greater than that found in aged rats regardless of diet. The age-related decrease in basal hepatic ME activity was not apparent in rats maintained on the high glucose or the high fructose diets, yet the T3 responsiveness of ME in rats maintained on these diets was not normalized. In adipose tissue, with the exception of the age-related changes in basal activity of the lipogenic enzymes, neither T3 nor the feeding of the test diets had any consistent effects. Since insulin resistance induced by high fructose feeding did not reduce hepatic lipogenic enzymes, it is unlikely that the age-related increase in insulin resistance explains the reduced lipogenic enzyme activity in aged rats. However, resistance to thyroid hormone action found in aged rats may partly account for the reduced hepatic lipogenic enzyme activity.
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PMID:The age-related changes in lipogenic enzymes: the role of dietary factors and thyroid hormone responsiveness. 1040 Mar 7

The impact of hyperthyroidism on epididymal glycosidases was studied in albino rats. Hyperthyroidism was induced in Wistar rats aged 30 days by daily injection of T4 (25 microg/100 g body weight/day intramuscularly) for 30 or 60 days; control rats were injected with vehicle (alkaline saline, pH 7.8). One set of hyperthyroid rats was reverted to euthyroid status by withdrawing T4 treatment after 30 days of hyperthyroidism. To asses the direct effect of thyroid hormone on epididymal hexosaminidases, caput, corpus and cauda tissues were stimulated with 25, 50 or 100 ng/mL T3 for 24 h, after an initial culture of 24 h. The activity of beta-glucosidase decreased in caput, corpus and cauda epididymis of hyperthyroid rats. beta-Galactosidase activity increased in the caput epididymis irrespective of the duration of hyperthyroidism. While a similar decrease occurred in the corpus and cauda epididymis in the 30 day hyperthyroid group, an opposite trend was observed in 60 day hyperthyroid rats. Caput beta-N-acetylglucosaminidase activities increased at both time points, whereas activity decreased in the corpus and cauda in 30 day, but increased in 60 day hyperthyroid rats. Hyperthyroidism consistently increased caput and corpus beta-N-acetylgalactosaminidase activity irrespective of the duration. Cauda epididymal beta-N-acetylgalactosaminidase activity was decreased in 30 day and increased in 60 day hyperthyroid rats. Hyperthyroidism induced changes in caput beta-galactosidase, beta-N-acetylgalactosaminidases, corpus beta-N-acetylglucosaminidase and cauda beta-N-acetylgalactosaminidase which were irreversible while the remaining actvities were brought back to normal when T4 treatment was withdrawn. In vitro studies showed that T3 stimulates epididymal hexosaminidases (beta-N-acetylglucosaminidase and beta-N-acetylgalactosaminidase) irrespective of the dose. These data suggest that thyroid hormones have a specific and direct influence on glycosidases in specific regions of the epididymis.
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PMID:Differential effect of hyperthyroidism on rat epididymal glycosidases. 1145 72

3,3',4,4'-Tetrachloroazobenzene is not commercially manufactured but is formed as an unwanted byproduct in the manufacture of 3,4-dichloroaniline and its herbicidal derivatives Propanil(R), Linuron(R), and Diuron(R). In addition, environmental contamination by 3,3',4,4'-tetrachloroazobenzene occurs from the degradation of chloranilide herbicides and the photolysis and biolysis of 3,4-dichloroaniline. 3,3',4,4'-Tetrachloroazobenzene was nominated by the United States Environmental Protection Agency for toxicity testing based on concerns over the potential for human exposure, the structural resemblance to 2,3,7,8-tetrachlorodibenzo-p-dioxin, and the reported dioxin-like effects of 3,3',4,4'-tetrachloroazobenzene. The toxicity of 3,3',4,4'- tetrachloroazobenzene was evaluated in 16-day and 13-week gavage studies in male and female F344/N rats and B6C3F1 mice. In addition to histopathology, evaluations included hematology (rats only), clinical chemistry, thyroid hormone analyses (rats only), cytochrome P(450)1A immunohistochemical staining in the liver (rats only), and assessments of male reproductive endpoints and estrous cycle length. Genetic toxicology studies included mutagenicity tests in Salmonella typhimurium and the determination of micronuclei in mouse bone marrow and peripheral blood erythrocytes. In the 16-day studies, groups of five male and five female rats received 3,3',4,4'-Tetrachloroazobenzene in corn oil by gavage 5 days a week at doses of 0, 12.5, 32, 80, 200, or 500 mg per kg body weight. Groups of five male and five female mice received 3,3',4,4'-Tetrachloroazobenzene in corn oil by gavage 5 days a week at doses of 0, 1, 3.2, 10, 32, or 100 mg/kg. Major effects included increases in liver, lung, and spleen weights of rats and liver and heart weights of mice and decreases in thymus weights of rats and mice. No effects were found on survival or mean body weight gains of rats or mice. Incidences of hematopoietic cell proliferation in the spleen were increased in all groups of dosed male rats, in female rats that received 32 mg/kg or greater, and in 100 mg/kg male and female mice. Renal tubule hyaline droplet accumulation in the cytoplasm of renal cortical epithelial cells and chronic nephropathy were observed microscopically in male rats in the 80, 200, and 500 mg/kg groups. Female mice in the 100 mg/kg group had atrophy of the thymus. In the 13-week studies, groups of 10 male and 10 female rats and mice received 3,3',4,4'-Tetrachloroazobenzene in corn oil by gavage 5 days a week at doses of 0, 0.1, 1, 3, 10, or 30 mg/kg. In the 13-week rat study, the major effects included a decrease in the mean body weight gain of 30 mg/kg females and final mean body weights of 30 mg/kg males and females, decreased thymus weights of males and females in the 10 and 30 mg/kg groups accompanied by thymic atrophy observed microscopically, increased incidences of hematopoietic cell proliferation in the spleen in 10 and 30 mg/kg males and females, a responsive anemia in 10 and 30 mg/kg males and females at week 13, and decreased platelet counts in 10 and 30 mg/kg males and females on day 21 and at week 13. Spleen weights were increased in 10 and 30 mg/kg males and females. Liver weights were increased in males that received 1 mg/kg or greater and in 10 and 30 mg/kg females. Furthermore, hepatic cytochrome P(450)1A staining presence and intensity were increased in 30 mg/kg males and females. Sharp decreases in circulating thyroxine concentrations were observed in males and females at all doses. In spite of this sharp decrease, thyroid-stimulating hormone concentrations were marginally increased. Incidences of hyperplasia of the forestomach were increased in males administered 3 mg/kg or greater and females administered 30 mg/kg. In the 13-week mouse study, the major effects included increases in liver and spleen weights of 10 and 30 mg/kg males and females and increased incidences of hyperplasia of the forestomach in males and females that received 1 mg/kg or greater. Furthermore, a decrease in thymus weight of 30 mg/kg males, an increase in centrilobular hypertrophy of hepatocytes in males that received 3 mg/kg or greater, and an increase in the incidences of hematopoietic cell proliferation in the spleen in males that received 3 mg/kg or greater were observed. A significant decrease in epididymal spermatozoal concentration was observed in 3 and 30 mg/kg males. 3,3',4,4'-Tetrachloroazobenzene was mutagenic in S. typhimurium strain TA97 in the presence of rat liver S9 activation enzymes; no mutagenic activity was detected in strain TA98, TA100, TA1535, or TA1537 with or without S9. In vivo, the frequency of micronucleated erythrocytes was significantly increased in peripheral blood samples from male and female mice given 3,3',4,4'-Tetrachloroazobenzene by gavage for 13 weeks. However, results of a 3-day exposure of up to 200 mg/kg by intraperitoneal injection did not demonstrate induction of micronuclei in bone marrow erythrocytes of male mice. In summary, 3,3',4,4'-Tetrachloroazobenzene caused typical dioxin-like effects, such as thymic atrophy, an increase in liver weights, induction of hepatic cytochrome P(450)1A, and decreased mean body weight gains. Furthermore, in the 13-week studies, a sharp decrease in circulating thyroxine concentrations was observed even at the lowest dose (0.1 mg/kg) tested in rats. Other effects included a decrease in epididymal spermatozoal concentration in mice, major effects on the hematopoietic system, and increased incidences of hyperplasia of the forestomach in 3 and 30 mg/kg males and 30 mg/kg females. A no-observable-adverse-effect-level (NOAEL) was not reached in rats. The NOAEL in mice was 0.1 mg/kg. Comparison of various dioxin-like effects in these studies with those reported in the literature indicate that 3,3',4,4'-Tetrachloroazobenzene is six to two orders of magnitude less potent than 2,3,7,8-tetrachlorodibenzo-p-dioxin.
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PMID:NTP Technical Report on the Toxicity Studies of 3,3',4,4'-Tetrachloroazobenzene (CAS No. 14047-09-7) Administered by Gavage to F344/N Rats and B6C3F1 Mice. 1198 82

3,3',4,4'-Tetrachloroazoxybenzene is not commercially manufactured but is present as a contaminant of 3,4-dichloroaniline and its herbicidal derivative Diuron(R). In addition, environmental contamination occurs when 3,3',4,4'-tetrachloroazoxybenzene is formed by the photolysis and biolysis of 3,4-dichloroaniline. 3,3',4,4'-Tetrachloroazoxybenzene was nominated by the United States Environmental Protection Agency for toxicity testing based on concerns over the potential for human exposure, the structural resemblance to 2,3,7,8-tetrachlorodibenzo-p-dioxin, and the reported dioxin-like effects of 3,3',4,4'-tetrachloroazoxybenzene. The toxicity of 3,3',4,4'-tetrachloroazoxybenzene was evaluated in 16-day and 13-week gavage studies in male and female F344/N rats and B6C3F1 mice. In addition to histopathology, evaluations included hematology (rats only), clinical chemistry, thyroid hormone analyses (rats only), hepatic cell proliferation (rats only), cytochrome P(450)1A immunohistological staining in the liver (rats only), and assessments of male reproductive endpoints and estrous cycle length. Additional genetic toxicology studies included mutagenicity tests in Salmonella typhimurium and the determination of micronuclei in mouse bone marrow and peripheral blood erythrocytes. In the 16-day studies, groups of five male and five female rats received 3,3',4,4'-tetrachloroazoxybenzene in corn oil by gavage at doses of 0, 12.5, 32, 80, 200, or 500 mg per kg body weight, 5 days a week. Groups of five male and five female mice received 0, 1, 3.2, 10, 32, or 100 mg/kg in corn oil by gavage, 5 days a week. Major effects in rats included increases in liver and lung weights, and decreases in mean body weights and body weight gains, heart weights, and thymus weights. Effects in mice included increases in liver weights and decreases in thymus weights. No effects on survival were observed. Treatment-related lesions included cytoplasmic alteration of hepatocytes, splenic hematopoietic cell proliferation, thymic atrophy, and nephropathy in rats and thymic atrophy, splenic hematopoietic cell proliferation, and hepatic foci of inflammation and necrosis in mice. In the 13-week studies, groups of 10 male and 10 female rats and mice received 3,3',4,4'- tetrachloroazoxybenzene in corn oil by gavage at doses of 0, 0.1, 1, 3, 10, or 30 mg/kg, 5 days a week. In the 13-week rat study, all males and seven females in the 30 mg/kg groups died. Decreases in final mean body weights and body weight gains were observed in 3 and 10 mg/kg males and 10 and 30 mg/kg females. Decreased thymus weights, accompanied by thymic atrophy observed microscopically, were observed at doses of 1 mg/kg or greater in males and females. Increased liver weights were observed in males and females administered 1 mg/kg or greater, and hepatic cytochrome P(450)1A staining was increased in 1 and 3 mg/kg males and 3, 10, and 30 mg/kg females. In addition, a responsive anemia and decreases in platelet counts were observed in dosed male and female rats. A marked decrease in circulating thyroxine concentrations was observed in dosed males and females. In spite of this sharp decrease, thyroid-stimulating hormone concentrations were marginally increased. A decrease in epididymal spermatozoal motility was observed in all dosed groups tested. In 10 mg/kg females, the estrous cycle length was increased. Major effects included increased incidences of hyperplasia of the forestomach in 3, 10, and 30 mg/kg males and 10 and 30 mg/kg females. Increased incidences of centrilobular degeneration and hematopoietic cell proliferation were observed in the liver of dosed males and females. Furthermore, chronic active inflammation of the lung vasculature and hematopoietic cell proliferation in the spleen were observed in dosed males and females. The increased severities of cardiomyopathy and nephropathy in males and the incidences of cardiomyopathy and nephropathy and severity of cardiomyopathy in females were 3,3',4,4'-tetrachloroazoxybenzene related. In the 13-week mouse study, the major effects included increases in liver weights in males administered 3 mg/kg or greater and females administered 1 mg/kg or greater. Hyperplasia of the forestomach and dilatation of hair follicles were observed in 10 and 30 mg/kg males and 30 mg/kg females. Furthermore, thymus weights were decreased in males administered 3 mg/kg or greater and in 10 and 30 mg/kg females. Increased incidences of centrilobular hypertrophy of hepatocytes were observed in 10 and 30 mg/kg males and females. Increased incidences of hematopoietic cell proliferation in the spleen were observed in 30 mg/kg males and in 10 and 30 mg/kg females. Increases in the incidences of thymocyte necrosis were observed in 10 mg/kg males and in 10 and 30 mg/kg females. The incidences of splenic pigmentation were increased in all dosed groups of males, and the severity of pigmentation increased with increasing dose in males and females. 3,3',4,4'-Tetrachloroazoxybenzene was not mutagenic in S. typhimurium strain TA97, TA98, TA100, or TA1535 with or without induced S9 metabolic activation enzymes. It did not induce significant increases in micronucleated erythrocytes in a three-exposure male mouse bone marrow micronucleus test up to dose levels of 200 mg/kg, but results of a 13-week peripheral blood micronucleus test conducted in male and female mice were positive. In summary, 3,3',4,4'-tetrachloroazoxybenzene caused typical dioxin-like effects, including thymic atrophy, increased liver weights, induction of hepatic cytochrome P(450)1A, and decreased mean body weight gains. Furthermore, a marked decrease in circulating thyroxine concentrations was observed in male and female rats, even at the lowest dose (0.1 mg/kg) in female rats. A decrease in epididymal sperm motility was observed at all doses in rats. Effects on the hematopoietic system occurred at doses including and lower than those that caused histopathologic alterations in the liver. A no-observable-adverse-effect-level (NOAEL) was not reached in rats. In male and female mice, the NOAEL was 1 and 0.1 mg/kg, respectively. Furthermore, treatment-related effects included increased incidences of hyperplasia of the forestomach epithelium in rats and mice, chronic active inflammation of the vasculature of the lung in rats, increased incidences and/or severities of cardiomyopathy and nephropathy in rats, and dilatation of the hair follicles in mice. Comparison of various dioxin-like effects in these studies with those reported in the literature indicate that 3,3',4,4'- tetrachloroazoxybenzene is six to two orders of magnitude less potent than 2,3,7,8-tetrachlorodibenzo-p-dioxin.
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PMID:NTP Technical Report on the Toxicity Studies of 3,3',4,4'-Tetrachloroazoxybenzene (CAS No. 21232-47-3) Administered by Gavage to F344/N Rats and B6C3F1 Mice. 1198 83


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