UMLS:C0002871 - FACTA Search

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Query: UMLS:C0002871 (anemia)
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The effect of the trypanocidal drug Novidium on elevated ejaculation time and deteriorated semen characteristics was studied in Zebu cattle infected with T. vivax and T. congolense. Two groups, comprising six bulls per group, were infected with Trypanosoma vivax or Trypanosoma congolense while three bulls served as controls. Chemotherapy was carried out 12 weeks post-infection on three bulls from each group, leaving three bulls untreated while three bulls served as uninfected controls. Blood samples from treated bulls were all negative for trypanosomes 3 days post-chemotherapy. The animals also had normal body temperature. As the study progressed, clinical signs associated with trypanosomiasis, such as anaemia and cachexia, disappeared gradually in treated bulls. There was some improvement in semen characteristics of some of the bulls at 10 weeks post-chemotherapy with Novidium. However, all bulls infected with T. vivax or T. congolense irrespective of Novidium chemotherapy still had poor semen characteristics manifested by all or some of the following: decreased volume of semen, oligospermia, azoospermia and elevated incidence of spermatozoa morphological abnormalities. They were thus unsuitable for breeding.
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PMID:Effect of chemotherapy on elevated ejaculation time and deteriorated semen characteristics consequent to bovine trypanosomiasis. 239 78

Progestagen-releasing IUDs were developed to diminish the problems of bleeding and pain with inert and copper-containing IUDs. The intrauterine release of the progestagen causes endometrial atrophy, resulting in impairment of nidation, and interferes with transport of the ovum and the spermatozoa. 2 available types, Progestasert, Biograviplan (Alza Corporation, California; Grunenthal) and Levonorgestrel Nova-T (Leiras Pharmaceuticals, Finland), have been sufficiently tested in multinational trials. Compared with Progestasert, LNG Nova-T showed lower pregnancy rates (Pearl Index 0.30), less risk for ectopic pregnancy, and a longer effective lifetime (7 years). With both IUDs, the amount and duration of menstrual blood loss is decreased. Amenorrhea is a frequently occurring side effect of LNG Nova-T, caused by endometrial atrophy. Intermenstrual blood loss and spotting incidences are not uniformly reduced and are still a frequent reason for removal. Preinsertion counseling may improve the acceptance of these nonhealth threatening side effects. With both IUDs, a decrease in menstrual cramps during periods is perceived and a low incidence of PID is found. Basically, the progestagen-releasing IUD can be recommended to all women who wish an IUD for contraception and to women with contraindications for OCs, especially to those with menorrhagia, anemia, or risk for anemia. (author's)
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PMID:Intrauterine steroid contraceptives. 313 66

The c-KIT proto-oncogene encodes for a transmembrane receptor and is associated with maturation of several cell types, including germ cells. The ligand of the receptor has been identified as stem cell factor (SCF). Loss or alteration of the expression of either of these factors leads to anemia, albinism, and/or sterility in mice. We examined the expression of c-KIT and SCF by immunohistochemistry in specimens from normal and infertile human testis. All specimens were obtained in the evaluation of male subfertility. We were able to demonstrate staining for c-KIT in Leydig cells in all specimens. Normal testis stained for c-KIT in the cytoplasm of early spermatogenic cells, as well as the acrosomal granules of the round spermatids and the acrosome of testicular spermatozoa. However, staining in testis demonstrating maturation arrest failed to demonstrate acrosomal staining, and Sertoli-only specimens demonstrated staining for c-KIT in Leydig cells only. The results for SCF demonstrated an overall uniform staining of Leydig cells in all specimens. The intensity of staining of Sertoli cells increased from normal to maturation arrest to Sertoli-only specimens. Germ cell staining was consistently negative. We hypothesize that these staining patterns for SCF are due to either lack of staining of the receptor-ligand complex or overexpression of the kit ligand in tissue that does not express the kit receptor. It appears that the c-kit receptor is expressed in the acrosome of developing germ cells, as well as in Leydig cells and early spermatogenic cells, suggesting a role in the acrosome reaction, as well as germ cell maturation and differentiation.
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PMID:Expression of c-KIT and its ligand, stem cell factor, in normal and subfertile human testicular tissue. 888 3

A total of 34 kidney transplant recipients (18 infertile and 16 fertile) and 31 nontransplant persons (15 infertile and 16 fertile) were included in this study. All subjects were assessed clinically and by measurement of basal concentrations of total testosterone, FSH, cyclosporine whole blood trough levels, serum creatinine, haemoglobin and semen analysis using computer-aided sperm analysis (CASA) as well as scrotal ultrasonography to evaluate testicular dimensions. Our results demonstrate a significant decrease (p < 0.05) in sperm concentration, the percentage of motile spermatozoa, straight line velocity (VSL), linearity (LIN) and velocity of average path (VAP) among infertile transplant patients in comparison with the fertile transplant group. Serum testosterone, FSH levels and testicular dimensions did not differ significantly (p > 0.05) between fertile and infertile transplant recipients. Both sperm concentration and VSL were inversely correlated to the cyclosporine whole blood trough levels (p < 0.05). The time spent on haemodialysis was inversely correlated (p < 0.05) with the percentage of motile spermatozoa and the amplitude of lateral head displacement (ALH). In conclusion, CASA is valuable in evaluation of sperm motility in infertile renal transplant patients. Stabilization of the cyclosporine whole blood trough level within the target therapeutic level and correction of anaemia (if any) could improve the fertility potential in kidney transplant recipients.
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PMID:Assessment of sperm motion characteristics in infertile renal transplant recipients using computerized analysis. 905 19

beta-Bromo-beta-nitrostyrene is a wide-spectrum biocide most frequently used as a fungicide to combat the formation of slime in paper and pulp mill operations. Toxicity studies were conducted by administering beta-bromo-beta-nitrostyrene (99% pure, trans isomer) to groups of 10 male and 10 female F344/N rats and B6C3F1 mice by gavage, 5 days per week for 4 weeks. Doses of 0, 37, 75, 150, 300, or 600 mg/kg were administered in a corn oil vehicle. The parameters evaluated included hematology, clinical chemistry (rats only), and histopathology. The genetic toxicity of b-bromo-b- nitrostyrene was evaluated in Salmonella typhimurium and in peripheral blood erythrocytes of mice. In addition, the absorption, distribution, metabolism, and excretion of b-bromo-b- nitrostyrene were studied in male F344 rats following intravenous, dermal, or oral administration. In the 4-week study in rats, two males in the 150 mg/kg group, one male and one female in the 300 mg/kg groups, and all rats in the 600 mg/kg groups died or were killed moribund before the end of the study. The mean body weight gains and absolute and relative thymus weights of male and female rats in the 300 mg/kg groups were lower than those of the controls. Hematology evaluations in rats indicated the development of a mild anemia and monocytosis consistent with and likely related to inflammatory and ulcerative lesions that occurred in the gastrointestinal tract. Clinical chemistry evaluations indicated lower alkaline phosphatase activities and serum total protein and albumin concentrations in treated rats than in the controls. Treatment-related lesions in rats were observed in the forestomach, glandular stomach, cecum, nasal passages, and testis. Males were generally affected at lower doses than females. The most prominent lesions were in the forestomach and were characterized by inflammation, hemorrhage, and necrosis in rats dying early. In rats surviving to the end of the study, forestomach lesions included necrosis, ulceration, and regenerative epithelial hyperplasia and hyperkeratosis. Inflammation of the glandular stomach and cecum also occurred in rats dying early. Inflammation and degeneration of the nasal passage in treated rats were attributed to reflux of the irritant chemical in the gavage fluid. Testicular degeneration was seen in rats dying early and was characterized by necrotic germ cells and a decreased number of spermatozoa in the epididymal tubules and by multinucleated syncytial cells in the seminiferous tubules. In the 4-week study in mice, one male in the 300 mg/kg group and all mice in the 600 mg/kg groups died or were killed moribund before the end of the study. No significant changes in final mean body weights or mean body weight gains were observed in males or females. Hematologic changes consistent with inflammatory lesions occurred in male and female mice in the 300 mg/kg groups. Treatment-related lesions in mice occurred in the forestomach, gallbladder, and testis. Forestomach lesions were similar to those described in rats and were only present in male and female mice given doses of 300 mg/kg or greater. At these dose levels, inflammation and degeneration/necrosis of the gallbladder mucosa also occurred in male and female mice, but these lesions were absent in the bile ducts or liver. Testicular degeneration occurred in mice dying early and was similar to that observed in rats. In comparative disposition and metabolism studies in male F344 rats, clear differences were found between the fate of b-bromo- b-nitrostyrene following oral administration and the fate of radiolabeled beta-bromo-beta-nitrostyrene following intravenous or dermal administration. Oral exposure resulted in significant absorption of nonhydrolyzed beta-bromo-beta-nitrostyrene and the formation of parent compound metabolites, primarily 1-phenyl-2-nitroethyl-1-sulfonic acid (PNSA), a product of a sulfation reaction at the alpha carbon. Following dermal exposure, a limited amount of beta-bromo-beta-nitrostyrene entered the systemic circulation (approximately 10% per 24 hours from a 10 mg/cm2 dose) although lower doses were more completely absorbed. Once beta-bromo-beta-nitrostyrene entered the circulation, significant amounts of the dose were hydrolyzed or bound to macromolecules. PNSA was not a major metabolite in dermal or intravenous studies. Regardless of the route of administration, only low levels of radioactive label from beta-bromo-beta-nitrostyrene were retained in tissues following exposure, and most beta-bromo-beta-nitrostyrene metabolites were excreted in the urine and feces within 24 to 48 hours. beta-bromo-beta-nitrostyrene was mutagenic in S. typhimurium strains TA98 and TA100 in the absence of exogenous metabolic activation (S9). No mutagenic activity was observed with S9 in either of these strains, and no mutagenic activity was observed in strains TA97 or TA1535, with or without S9. The frequency of micronucleated normochromatic erythrocytes was significantly increased in the peripheral blood of male mice, but not female mice, following 4 weeks of exposure to beta-bromo-beta-nitrostyrene by corn oil gavage. In summary, under the conditions of these 4-week gavage studies, rats were more sensitive to the toxic and irritant effects of beta-bromo-beta-nitrostyrene than mice, and males were more affected by beta-bromo-beta-nitrostyrene than females. Although the specific cause of the early deaths could not be determined, significant inflammation and necrosis developed in the forestomach of rats and mice, in the glandular stomach and cecum of rats, and in the gallbladder of mice. Similar lesions in the nasal passages of rats were attributed to reflux of gavage materials. The no-observed- adverse-effect level (NOAEL) for histopathologic lesions was 37 mg/kg per day for rats and 150 mg/kg per day for mice.
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PMID:NTP Toxicity Studies of beta-Bromo-beta-Nitrostyrene (CAS No. 7166-19-0) Administered by Gavage to F344/N Rats and B6C3F1 Mice. 1196 39

Dibutyl phthalate is a phthalate ester with extensive use in industry in such products as plastic (PVC) piping, various varnishes and lacquers, safety glass, nail polishes, paper coatings, dental materials, pharmaceuticals, and plastic food wrap. Concomitant with this extensive worldwide use is the high potential for human exposure to dibutyl phthalate in the workplace and the home environment through direct sources as well as indirectly, through contamination of water, air, and foodstuffs. Because existing toxicity information was considered inadequate, the effects of exposure to dibutyl phthalate were examined in male and female F344/N rats and B6C3F1 mice in 13-week feed studies. Furthermore, due to concern over the potential for pervasive exposure of humans to dibutyl phthalate, additional perinatal studies examined rats and mice exposed as pups in utero, for the 4 weeks of lactation, and for an additional 4 weeks postweaning. Additional studies examined the effects on rats of combining perinatal and adult subchronic exposure. Due to the recognized biologic activity of this and other phthalates, hepatic peroxisome proliferation during the in utero and lactational phases and testicular toxicity during the perinatal period were also examined. Finally, reproductive assessment by continuous breeding (including crossover mating trials and offspring assessment) and genetic toxicity studies were also conducted. In the maximum perinatal exposure (MPE) determination study in rats, dibutyl phthalate was administered in the diet to dams during gestation and lactation, and to the pups postweaning for four additional weeks, at concentrations of 0, 1,250, 2,500, 5,000, 7,500, 10,000, and 20,000 ppm. Decreased weight gains were noted in dams exposed to 20,000 ppm during gestation and to dams exposed to 10,000 ppm during lactation. The gestation index (number of live pups per breeding female) was significantly lower in the 20,000 ppm group than in the controls, and pup mortality in this group was marked (100% by Day 1 of lactation); however, survival was 89% or greater in all other treatment groups. The mean body weight of pups in the 10,000 ppm group at Day 28 of lactation was approximately 90% of the mean weight of control pups. Pups were weaned onto diets containing dibutyl phthalate at the same concentrations fed to dams. After an additional 4 weeks of dietary administration, final mean body weights of pups in the 10,000 ppm groups were 92% of the control value for males and 95% of the control value for females. Hepatomegaly (increased relative liver weight) was observed in males in all exposed groups and in females receiving 2,500 ppm or greater. No gross lesions were observed at necropsy. Moderate hypospermia of the epididymis was diagnosed in all male rats in the 7,500 and 10,000 ppm groups; mild hypospermia of the epididymis was diagnosed in 2 of 10 males in the 5,000 ppm group. No degeneration of the germinal epithelium was detected in the testis of these rats. Thus, although toxicologically important, the epididymal hypospermia was not considered to be life threatening, and 10,000 ppm was recommended as the MPE concentration for male and female rats. In the subsequent subchronic toxicity study of dibutyl phthalate with perinatal exposure, dams were administered diets containing 0 or the MPE concentration (10,000 ppm) during gestation and lactation, and weaned pups were administered the same diets as their dams received for an additional 4 weeks, until the beginning of the 13-week exposure phase. Male and female rats then received diets containing dibutyl phthalate at concentrations of 0, 2,500, 5,000, 10,000, 20,000, and 40,000 ppm for 13 weeks. No mortality or toxicity was observed in dams during the perinatal phase of the study; however, before pups were culled at 4 days postpartum, the percentage of live pups per litter was 86% to 93% that of the controls. Through weaning, litter weights of exposed pups ranged from 89% to 92% of the control values. Ten control and ten exposed pups per sex were examined at the time of trol and ten exposed pups per sex were examined at the time of weaning; hepatomegaly and markedly increased peroxisomal enzyme activities (approximately 9-fold greater than the control values) were observed in exposed pups. Body weights of the perinatally exposed pups remained lower than those of the controls throughout the 4-week period before the 13-week adult exposures began. During the 13-week adult exposure phase, the final mean body weight of males in the MPE: 0 ppm control group (MPE rats, returned to the base diet for 13 weeks), was 95&percnt; that of the controls. The body weight gain of females in the MPE:0 ppm group was greater than that of the unexposed controls, and the final body weights of these two groups were similar. Body weight gains of rats treated with dibutyl phthalate as adults decreased with increasing exposure concentration; for rats that received the MPE concentration followed by 40,000 ppm for 13 weeks, final body weights were 51&percnt; of the control value for males and 74&percnt; of the control value for females. Hepatomegaly apparently regressed in rats in the MPE:0 ppm groups but was observed in male rats receiving 5,000 ppm or greater and in females receiving 2,500 ppm or greater. In males that received 20,000 ppm as adults, testis and epididymal weights were less than in the controls; males in the 40,000 ppm group also had a lower testis weight than the controls. Results of hematologic analyses conducted at the end of the 13-week exposure period suggested a mild anemia in male rats administered 10,000 ppm or greater as adults and female rats administered 40,000 ppm as adults. Hypocholesterolemia and hypotriglyceridemia were observed in male and female rats at the higher exposure concentrations. Hypotriglyceridemia was detected in females receiving 20,000 or 40,000 ppm and in males receiving 10,000 ppm or greater. Elevations in alkaline phosphatase activities and bile acid concentrations in male and female rats receiving 20,000 or 40,000 ppm as adults were indicative of cholestasis. Microscopic examination revealed hepatocellular cytoplasmic alteration, consistent with glycogen depletion, in male and female rats receiving a concentration of 10,000 ppm or greater. In the liver of rats receiving 40,000 ppm, small, fine, eosinophilic granules were also observed in the cytoplasm of hepatocytes. Ultrastructural examination suggested the presence of increased numbers of peroxisomes. Lipofuscin accumulation was detected in rats that received 10,000 ppm or greater. Consistent with the regression of the hepatomegaly in rats in the MPE:0 and MPE:2,500 ppm groups, peroxisomal enzyme activity was not elevated in these groups. Marked elevations of peroxisomal enzyme activity were detected, however, in males receiving 5,000 ppm or greater and in females receiving 10,000 ppm or greater; at the 40,000 ppm concentration, the highest concentration tested, enzyme activities were approximately 20 fold greater than the control values. Histopathologic examination of the testes revealed degeneration of the germinal epithelium, a mild to moderate focal lesion in rats in the 10,000 and 20,000 ppm groups and a marked, diffuse lesion in all males receiving 40,000 ppm; at 40,000 ppm, an almost complete loss of the germinal epithelium resulted. Testicular zinc concentrations were lower in the 40,000 ppm group than in the controls, a finding consistent with the marked loss of germinal epithelium at this exposure concentration. Spermatogenesis was evaluated in rats in the 0, 2,500, 10,000, and 20,000 ppm groups; rats administered 20,000 ppm had fewer spermatid heads per testis than the unexposed controls, and epididymal spermatozoal concentration was less than that in the MPE:0 ppm group. For comparison with the perinatal subchronic study, a standard 13-week evaluation of the toxicity of dibutyl phthalate in male and female rats was also conducted. In this study, rats received dibutyl phthalate at the same dietary concentrations used in the 13-week exposure phase of the study with perinatal exposure: 0, 2,500, 5,000, 10,000, 20,000, and 40,000 ppm. No deaths occurred in the standard study. Markedly reduced final mean body weights were observed in males and females in the 40,000 ppm groups (45&percnt; and 73&percnt; of control body weights, respectively); final mean body weights of males receiving 10,000 ppm or greater and females receiving 20,000 ppm or greater were lower than those of the controls. Hepatomegaly was observed in males that received 5,000 ppm or greater and in females that received 10,000 ppm or greater. Testis and epididymal weights of males in the 20,000 and 40,000 ppm groups were lower than those of the controls. A minimal anemia was detected in male rats receiving 5,000 ppm or greater. Hypocholesterolemia was observed in male and female rats receiving 20,000 or 40,000 ppm, and hypotriglyceridemia was detected in males in all exposed groups and in females receiving 10,000 ppm or greater. Elevations in alkaline phosphatase activity and bile acid concentration in male and female rats were considered indicative of cholestasis. Morphologic evaluation again confirmed the toxicity of dibutyl phthalate to the liver and testes of rats. Microscopic examination of the liver revealed hepatocellular cytoplasmic alterations, consistent with glycogen depletion, in male and female rats receiving 10,000 ppm or greater. In the liver of rats in the 40,000 ppm groups, small, fine, eosinophilic granules were also observed in the cytoplasm of hepatocytes. Ultrastructural examination suggested the presence of increased numbers of peroxisomes, and peroxisomal enzyme activity was elevated in the livers of male and female rats administered 5,000 ppm or greater; the enzyme activities in the 40,000 ppm groups were approximately 13-fold greater than the control value for males and 32-fold greater than the control value for females. Lipofuscin accumulation was detected in rats receiving 10,000 ppm or greater. Histopathologic examination of the testes revealed degeneration of the germinal epithelium, a mild to marked focal lesion in the 10,000 and 20,000 ppm groups and a marked, diffuse lesion in all males in the 40,000 ppm group; at 40,000 ppm, an almost complete loss of the germinal epithelium resulted. Testicular zinc concentrations were lower in the 20,000 and 40,000 ppm groups than in the controls. Serum testosterone values were also lower at these concentrations than in the controls. Spermatogenesis was evaluated in males in the 0, 2,500, 10,000, and 20,000 ppm groups; at 20,000 ppm, spermatid heads per testis and per gram testis, epididymal spermatozoal motility, and the number of epididymal spermatozoa per gram epididymis were lower than in the controls. All of these findings are consistent with the marked loss of germinal epithelium at these exposure concentrations. In the continuous breeding study, Sprague-Dawley rats received 0, 1,000, 5,000, or 10,000 ppm dibutyl phthalate in feed. Mean body weights of exposed dams at delivery and during lactation generally decreased with increasing exposure concentration. The mean pup weight at birth in the 10,000 ppm group was significantly lower than the control pup weight. The average number of live pups per litter in all exposed groups was lower than in the controls. Crossover mating trials in the F(0) generation revealed no effects on the fertility of male or female rats receiving 10,000 ppm. In contrast to the F(0) rats, mating, pregnancy, and fertility indices of F(1) rats were lower in the 10,000 ppm group than in the controls. Germinal epithelial degeneration of the testes and absence or under development of the epididymides were noted in F(1) males in the 10,000 ppm group. Interstitial cell hyperplasia was noted in 7 of 10 males in the 10,000 ppm group. These effects document the male and female reproductive toxicity of dibutyl phthalate in F(1) rats receiving 10,000 ppm and do not exclude the possibility of developmental toxicity to F2 offspring. In the MPE determination study in mice, dams received 0, 1,250, 2,500, 5,000, 7,500, 10,000, or 20,000 ppm dibutyl phthalate in feed during gestation and lactation; pups were weaned onto the same diets as the dams received and were exposed for an additional 4 weeks. The gestation period was longer in dams that received 2,500 ppm or greater than in the controls, and gestational body weight gain depressions were noted in dams receiving 7,500 ppm or greater. Only 5 of 20 females in the 10,000 ppm group delivered live pups, and none of the 20 females receiving 20,000 ppm delivered live pups. Only one pup in the 10,000 ppm group survived past Lactation Day 1; the number of live pups per litter in the 7,500 ppm group also remained low throughout lactation. No deaths of either male or female pups occurred after weaning. Initial (postweaning) and final body weights of male pups receiving 2,500 ppm or greater were significantly less than those of the control group. The mean body weights of exposed female pups were similar to the control body weight at weaning and remained similar throughout the 4 weeks postweaning. Hepatomegaly was present in male mice in all exposed groups, and the absolute liver weight of males administered 7,500 ppm was greater than that of the controls; although a similar change was apparent in females, no statistical differences between the liver weights of exposed and control females were detected. No treatment-related gross lesions were identified at necropsy, and no histopathologic lesions definitively associated with treatment were observed in male or female mice in the 7,500 ppm groups. The one surviving male pup in the 10,000 ppm group had cytoplasmic alteration in the liver, consistent with peroxisome proliferation. Developmental toxicity and fetal and pup mortality were suggested at concentrations as low as 7,500 ppm. No subchronic toxicity study with prior MPE exposure was conducted with mice, although an MPE concentration of 5,000 ppm was suggested by the data. In a standard 13-week toxicity study, mice received 0, 1,250, 2,500, 5,000, 10,000, or 20,000 ppm dibutyl phthalate in feed. No deaths occurred during this study. Mean body weights and weight gains of male and female mice decreased with increasing exposure concentration, and the decreases were significant for males and females that received 5,000 ppm or greater. Relative liver weights were greater in males and females receiving 5,000 ppm or greater than in the controls. A minimal anemia was suggested in female mice in the 20,000 ppm group. Although no gross lesions were observed at necropsy, microscopic examination revealed hepatocellular cytoplasmic alterations, consistent with glycogen depletion, in male mice receiving 10,000 or 20,000 ppm and female mice receiving 20,000 ppm. Small, fine, eosinophilic granules, consistent with peroxisome proliferation, were also observed in the cytoplasm of hepatocytes in males and females in the 20,000 ppm groups. Lipofuscin accumulation in the liver was detected in mice receiving 10,000 ppm or greater. In a continuous breeding study using Swiss (CD-1®) mice, animals received 0, 300, 3,000, or 10,000 ppm dibutyl phthalate in feed. The fertility index, average number of litters per breeding pair, and average number of live pups per litter in the 10,000 ppm group were lower than in the controls. Crossover mating trials of mice receiving 10,000 ppm revealed effects on dams in the F(0) generation, with a lower fertility index, number of live pups per litter, and pup weight than in the controls. Liver weights were greater in males and females, and the uterine weight was less in exposed dams than in the controls. No other changes were observed at necropsy or on histopathologic examination. These data document the female reproductive toxicity of dibutyl phthalate in F(0) mice. Dibutyl phthalate was not mutagenic in Salmonella typhimurium strain TA98, TA100, TA1535, or TA1537 with or without exogenous metabolic activation but did induce mutations in L5178Y mouse lymphoma cells treated without metabolic activation. In peripheral blood samples obtained from male and female mice at the end of the 13-week study, frequencies of micronucleated normochromatic erythrocytes were similar between exposed and control mice. Together, the studies in rodents suggest that young rodents (in utero and perinatal) respond in a manner qualitatively similar to that of adult rats and mice. Dibutyl phthalate induced toxic effects in rodents as pups in utero and during the lactational phases of development and also affected young adults, as evidenced by fetotoxicity and lethality, body weight gain decrements, increased liver weights, hepatic peroxisome proliferation, testicular toxicity, and female reproductive toxicity. Dibutyl phthalate was lethal to rat fetuses and rat and mouse neonates at dietary concentrations that were not toxic to dams. Otherwise, there was no teratogenic or morphologic evidence that rodent young were uniquely sensitive to the effects of short-term dibutyl phthalate treatment. Synonyms: 1,2-Benzenedicarboxylic acid dibutyl ester; benzene-o-dicarboxylic acid di-n-butyl ester; o-benzenedicarboxylic acid dibutyl ester; butyl phthalate; n-butyl phthalate; DBP; dibutyl 1,2-benzene dicarboxylate; dibutylphthalate; di-n-butylphthalate; di(n-butyl) phthalate; dibutyl-o-phthalate; phthalic acid dibutyl ester. Trade Names: Celluflex DBP; Elaol; Ergoplast FDB; Ersoplast FDA; Genoplast B; Hexaplas M/B; Palatinol C; Polycizer DBP; PX 104; RC Plasticizer DBP; Staflex DBP; Uniflex DBP; Unimoll DB; Witcizer 300; Witicizer 300. (NOTE: These studies were supported in part by funds from the Comprehensive Environmental Response, Compensation, and Liability Act trust fund (Superfund) by an interagency agreement with the Agency for Toxic Substances and Disease Registry, U.S. Public Health Service.)
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PMID:NTP technical report on the toxicity studies of Dibutyl Phthalate (CAS No. 84-74-2) Administered in Feed to F344/N Rats and B6C3F1 Mice. 1220 94

Gallium arsenide is used primarily to make light- emitting diodes, lasers, laser windows, and photodetectors and in the photoelectronic transmission of data through optical fibers. Gallium arsenide was nominated for study because of its widespread use in the microelectronics industry, the potential for worker exposure, and the absence of chronic toxicity data. Male and female F344/N rats and B6C3F1 mice were exposed to gallium arsenide particles (greater than 98% pure; mass median aerodynamic diameter = 0.8 to 1.0 &mgr;m) by inhalation for 16 days, 14 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, and the frequency of micronuclei was determined in the peripheral blood of mice exposed to gallium arsenide for 14 weeks. 16-DAY STUDY IN RATS: Groups of five male and five female rats were exposed to particulate aerosols of gallium arsenide with a mass median aerodynamic diameter of approximately 1 &mgr;m at concentrations of 0, 1, 10, 37, 75, or 150 mg/m(3) by inhalation, 6 hours per day, 5 days per week, for 16 days. All rats survived to the end of the study. The final mean body weights of all exposed groups of males and females were similar to those of the chamber controls. Compared to chamber controls, the liver and lung weights of males exposed to 1 mg/m(3) or greater and females exposed to 10 mg/m(3) or greater were increased; the thymus weights of all exposed groups of males were decreased. Gallium arsenide particles were visible in the alveolar spaces and, to a lesser extent, within alveolar macrophages of exposed rats. Moderate proteinosis (surfactant mixed with small amounts of fibrin) and minimal histiocytic cellular infiltrate were observed in the alveoli of exposed males and females. Epithelial hyperplasia and squamous metaplasia of the larynx were observed primarily in males exposed to 150 mg/m(3). 16-DAY STUDY IN MICE: Groups of five male and four or five female mice were exposed to particulate aerosols of gallium arsenide with a mass median aerodynamic diameter of approximately 1 &mgr;m at concentrations of 0, 1, 10, 37, 75, or 150 mg/m(3) by inhalation, 6 hours per day, 5 days per week, for 16 days. The final mean body weights were similar among exposed and chamber control groups. Compared to chamber controls, the lung weights of males and females exposed to 10 mg/m(3) or greater were increased. Gallium ar senide particles were visible in alveolar spaces and macrophages in some mice exposed to 150 mg/m(3). Moderate proteinosis, mild epithelial hyperplasia, and histiocytic infiltration of the lung were observed in males and females exposed to 10 mg/m(3) or greater. In the larynx, mild squamous metaplasia was seen in mice exposed to 10 mg/m(3) or greater, and mild chronic inflammation occurred in mice exposed to 75 or 150 mg/m(3). 14-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were exposed by inhalation to gallium arsenide particulate at concentrations of 0, 0.1, 1, 10, 37, or 75 mg/m(3), 6 hours per day, 5 days per week, for 14 weeks. All rats survived until the end of the study. The final mean body weight and body weight gain of males exposed to 75 mg/m(3) were significantly less than those of the chamber controls. Hematology and clinical chemistry results indicated that exposure to gallium arsenide induced a microcytic responsive anemia with an erythrocytosis and increased zinc protoporphyrin/heme ratios in exposed groups of rats. There were also increases in platelet and neutrophil counts, a transient decrease in leukocyte counts, and increases in the serum activities of alanine aminotransferase and sorbitol dehydrogenase. These changes were of greater magnitude in male rats. The lung weights of all exposed groups of rats were increased, while testis, cauda epididymis, and epididymis weights of males exposed to 37 or 75 mg/m(3) were generally less than those of chamber controls. Total spermatid heads and spermatid counts were significantly decreased in males exposed to 75 mg/m(3), while epididymal spermatozoa motility was significantly reduced in males ees exposed to 10 mg/m(3) or greater. Gallium arsenide particles were visible in alveolar spaces and macrophages in the lungs of exposed rats. Minimal to marked proteinosis and minimal histiocytic cellular infiltration of the alveoli were observed in all exposed groups; minimal squamous metaplasia in the larynx and lymphoid cell hyperplasia of the mediastinal lymph node were observed in some males and females exposed to 37 or 75 mg/m(3). Exposure-related increases in the incidences of plasma cell hyperplasia of the mandibular lymph node, testicular atrophy, epididymal hypospermia, bone marrow hyperplasia (males), and hemosiderosis in the liver were observed in the 37 and 75 mg/m(3) groups. 14-WEEK STUDY IN MICE: Groups of 10 male and 10 female mice were exposed by inhalation to gallium arsenide particulate at concentrations of 0, 0.1, 1, 10, 37, or 75 mg/m(3), 6 hours per day, 5 days per week, for 14 weeks. One female mouse exposed to 75 mg/m(3) died before the end of the study. Final mean body weights and body weight gains of males in the 75 mg/m(3) group were signifi cantly less than the chamber controls. Hematology and clinical chemistry results indicated that exposure to gallium arsenide affected the circulating erythroid mass and induced a microcytic responsive anemia with an erythrocytosis and increased zinc protoporphyrin/heme ratios in male and female mice. There were also increases in platelet and neutrophil counts. Compared to the chamber controls, the lung weights of males exposed to 1 mg/m(3) or greater and females exposed to 10 mg/m(3) or greater were increased. Testis, cauda epididymis, and epididymis weights, total spermatid heads, spermatid counts, and concentration and motility of epididymal spermatozoa were generally decreased. Gallium arsenide particles were visible in alveolar spaces and macrophages in the lungs of mice exposed to 1 mg/m(3) or greater. Mild to marked proteinosis, histiocytic infiltration, and epithelial hyperplasia were observed in the alveoli of males and females exposed to 1 mg/m(3) or greater. Minimal to mild suppurative inflammation and granuloma in the lung and squamous metaplasia in the larynx were present in males and females exposed to 10 mg/m(3) or greater. Min imal hyperplasia was observed in the tracheobronchial lymph node of males exposed to 10 mg/m(3) or greater and females exposed to 37 or 75 mg/m(3). Exposure- related increases in the incidences of testicular atrophy, epididymal hypospermia, hematopoietic cell proliferation of the spleen, and hemosiderosis of the liver and spleen were observed in groups of male and female mice exposed to 10 mg/m(3) or greater. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were exposed by inhalation to gallium arsenide particulate at concentrations of 0, 0.01, 0.1, or 1.0 mg/m(3), 6 hours per day, 5 days per week, for 105 weeks. Survival and Body Weights: Survival of exposed male and female rats was similar to the chamber controls. Mean body weights of males exposed to 1.0 mg/m(3) were generally less than those of the chamber controls throughout the study; females exposed to 1.0 mg/m(3) had slightly lower mean body weights during the second year. Pathology Findings: Compared to the chamber controls, the incidences of alveolar/bronchiolar neoplasms were significantly increased in females exposed to 1.0 mg/m(3) and exceeded the historical control ranges. Exposure-related nonneoplastic lesions in the lungs of male and female rats included atypical hyperplasia, alveolar epithelial hyperplasia, chronic active inflammation, proteinosis, and alveolar epithelial metaplasia. In the larynx of males exposed to 1.0 mg/m(3), the incidences of hyperplasia, chronic active inflammation, squamous metaplasia, and hyperplasia of the epiglottis were significantly increased. The incidences of benign pheochromocytoma of the adrenal medulla occurred with a positive trend in female rats, and the incidence was significantly increased in the 1.0 mg/m(3) group and exceeded the historical control range. The incidence of mononuclear cell leukemia was significantly increased in females exposed to 1.0 mg/m(3) and exceeded the historical control range. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were exposed by inhalation to gallium arsenide particulate at concentrations of 0, 0.1, 0.5, or 1.0 mg/m(3), 6 hours per day, 5 days per week, for 105 (males) or 106 (females) weeks. Survival and Body Weights: Survival of male and female mice was similar to the chamber controls. Mean body weights of exposed groups of males were similar to those of the chamber controls throughout the study; mean body weights of exposed groups of females were greater than those of the chamber controls from week 13 until the end of the study. Pathology Findings: Exposure-related nonneoplastic lesions in the lung of all groups of exposed mice included suppurative focal inflammation, chronic focal inflammation, histiocyte cellular infiltration, alveolar epithelial hyperplasia, and proteinosis. Increased incidences of minimal lymphoid hyperplasia of the tracheobronchial lymph node occurred in mice exposed to 1.0 mg/m(3) and in 0.5 mg/m(3)mg/m(3) males. GENETIC TOXICOLOGY: Gallium arsenide was not mutagenic in several strains of Salmonella typhimurium, with or without S9 metabolic activation enzymes, and no increase in the frequency of micronucleated erythrocytes was observed in peripheral blood of male or female mice exposed to gallium arsenide by inhalation for 14 weeks. CONCLUSIONS: Under the conditions of these 2-year inhalation studies, there was no evidence of carcinogenic activity of gallium arsenide in male F344/N rats exposed to 0.01, 0.1, or 1.0 mg/m(3). There was clear evidence of carcinogenic activity in female F344/N rats based on increased incidences of benign and malignant neoplasms in the lung. Increased incidences of benign neoplasms of the adrenal medulla and increased incidences of mononuclear cell leukemia were also considered to be exposure related. There was no evidence of carcinogenic activity in male or female B6C3F1 mice exposed to 0.1, 0.5, or 1.0 mg/m(3). Exposure to gallium arsenide caused a spectrum of nonneoplastic lesions in the lung of rats and mice, the larynx of male rats and hyperplasia of the tracheobronchial lymph node in mice. Synonym: Gallium monoarsenide.
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PMID:NTP Toxicology and Carcinogenesis Studies of Gallium Arsenide (CAS No. 1303-00-0) in F344/N Rats and B6C3F1 Mice (Inhalation Studies). 1256 48

o-Nitroanisole is used as an intermediate for the preparation of o-anisidine and in the manufacture of azo dyes. Toxicology and carcinogenesis studies were conducted by administering o-nitroanisole (>99% pure) in the diet to groups of male and female F344 rats and B6C3F1 mice for 14 days, 13 weeks, and 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, Chinese hamster ovary cells, and mouse lymphoma cells. 14-DAY STUDIES: Groups of five male and five female F344 rats received diets containing 0, 583, 1,166, 2,332, 4,665, or 9,330 ppm o-nitroanisole. Mean body weight gains and final mean body weights of males in the 4,665 and 9,330 ppm groups were lower than those of the controls. Absolute liver weights were significantly increased in males receiving 1,166 ppm or more and in females receiving 583 ppm or more. Groups of five male and five female B6C3F1 mice received diets containing 0, 250, 500, 1,000, 2,000, or 4,000 ppm o-nitroanisole. Mean body weight gains and final mean body weights of males that received 250 ppm and females that received 4,000 ppm were significantly lower than those of the controls. No other chemical-associated effects were observed. 13-WEEK STUDIES: Groups of 10 male and 10 female F344 rats received diets containing 0, 200, 600, 2,000, 6,000, or 18,000 ppm o-nitroanisole. Final mean body weights and feed consumption by male and female rats receiving 6,000 and 18,000 ppm were lower than those of the controls. Hemoglobin and hematocrit values were significantly lower and methemoglobin levels significantly higher in males in the 6,000 and 18,000 ppm groups than in controls. Absolute liver weights were significantly increased in females that received 200, 600, 2,000, and 6,000 ppm, absolute kidney weights were significantly increased in males that received 600, 2,000, and 6,000 ppm, and absolute spleen weights were significantly increased in males and females that received 6,000 and 18,000 ppm. Groups of 10 male and 10 female B6C3F1 mice received diets containing 0, 60, 200, 600, 2,000, or 6,000 ppm o-nitroanisole. Final mean body weight gains, final mean body weights, and feed consumption by male and female mice receiving 6,000 ppm were lower than those of the controls. Hemoglobin and hematocrit values in males and females that received 2,000 or 6,000 ppm were significantly lower than those in the controls. The absolute and relative liver weights of females in the 600 ppm group and relative liver weights of males and females in the 2,000 and 6,000 ppm groups were significantly greater than those of controls. Lesions associated with exposure to o-nitroanisole were present in the urinary bladder, spleen, kidney, liver, testis, and uterus of rats. Diffuse hyperplasia of the transitional epithelium of the urinary bladder occurred in all male and female rats that received 6,000 and 18,000 ppm. A transitional cell papilloma occurred in one male and transitional cell carcinomas occurred in two males and three females receiving 18,000 ppm. Congestion of the red pulp and capsular hyperplasia of the spleen and hepatocellular hypertrophy of the liver were present in males and females from the 18,000 ppm groups. Multifocal degeneration and necrosis of the renal tubule epithelium with infiltration of mononuclear inflammatory cells were present in male rats that received 600, 2,000, and 6,000 ppm. At the 18,000 ppm level, degeneration of the seminiferous epithelium accompanied by loss of spermatogenic cells and decreased numbers of spermatozoa were observed in the testes of male rats, while uterine atrophy was observed in female rats. Hepatocyte hypertrophy of the centrilobular and midzonal regions of liver lobules was present in mice that received 200 ppm and increased in severity at higher exposure levels. 2-YEAR STUDIES: The doses selected for the 2-year study of o-nitroanisole in rats were based on lower mean body weights, reduced feed consumption, and increased severity of regenerative anemia in male and female rats receiving 6,000 and 18,000 ppm during the 13-week study. Groups of 6roups of 60 male and 60 female F344 rats received diets containing 0, 222, 666, or 2,000 ppm o-nitroanisole. Groups of 60 male and 60 female B6C3F1 mice received diets containing 0, 666, 2,000, or 6,000 ppm o-nitroanisole. After 15 months, up to 10 animals from each group were evaluated for chemical-related lesions. Survival, Body Weights, Feed Consumption, and Clinical Findings: Survival of male rats receiving 2,000 ppm was significantly lower than that of the controls due to increased severity of nephropathy. Survival of 222 and 666 ppm male rats and all exposed female rats was similar to that of the controls. Survival of groups of exposed male and female mice was similar to that of the controls. The final mean body weight of male rats receiving 2,000 ppm was lower than that of the controls. Final mean body weights of male and female mice that received 2,000 and 6,000 ppm were lower than those of the controls. Feed consumption by male and female rats was similar to that by the controls. The only clinical finding in male or female mice attributable to chemical administration was discolored urine. Neoplasms and Nonneoplastic Lesions: The incidence of mononuclear cell leukemia was significantly increased in male rats that received 666 and 2,000 ppm and in female rats that received 2,000 ppm (males: 0 ppm, 26/50; 222 ppm, 25/50; 666 ppm, 42/50; 2,000 ppm, 34/50; females: 14/50, 11/50, 14/50, 26/50). Nephropathy occurred in all male rats; the severity increased with exposure level. Focal hyperplasia of the renal tubule epithelium was present in three males receiving 222 ppm and two males receiving 2,000 ppm. Renal tubule adenomas occurred in one male from each of the 222, 666, and 2,000 ppm groups, and renal tubule carcinomas occurred in two males from the 2,000 ppm group. Focal hyperplasia of the transitional epithelium of the urinary bladder was present in one female rat that received 222 ppm and two male rats and six female rats that received 2,000 ppm. A transitional cell papilloma occurred in the urinary bladder of one female rat from the 2,000 ppm group, and a transitional cell carcinoma occurred in another female from the 2,000 ppm group. The incidence of forestomach ulcers increased in male rats that received 2,000 ppm, and the incidence of focal hyperplasia of the forestomach increased with exposure level in male and female rats. In addition, squamous cell papillomas of the forestomach were present in one female receiving 222 ppm, one male receiving 666 ppm, and one male and one female receiving 2,000 ppm, while squamous cell carcinomas were present in one male receiving 666 ppm and one male and one female receiving 2,000 ppm. The incidences of pituitary gland adenomas in male rats and mammary gland fibroadenomas in female rats decreased with exposure level. The incidence of cellular alteration in the liver was significantly increased in exposed groups of male and female mice. The incidences of hepatocellular adenoma, hepatocellular adenoma or carcinoma (combined), and hepatocellular carcinoma or hepatoblastoma (combined) were significantly increased in male mice receiving 2,000 and 6,000 ppm. The incidences of hepatocellular adenoma or carcinoma were significantly increased in female mice that received 2,000 ppm. STOP-EXPOSURE STUDY: Groups of 60 male and 60 female F344 rats received diets containing 0, 6,000, or 18,000 ppm o-nitroanisole for 27 weeks and were then maintained on control feed without further chemical exposure for up to an additional 77 weeks. Up to 10 rats from each group were evaluated for the presence of chemical-related lesions at 3, 6, 9, and 15 months. Survival and Body Weights: Survival of exposed male and female rats was significantly lower than that of the controls as a result of moribund deaths associated with significantly increased incidences of urinary bladder neoplasms, primarily transitional cell carcinomas. All male rats that received 18,000 ppm were dead by week 48 and all females that received 18,000 ppm were dead by week 61. Mean body weights of exposed male and female rats were lower than those of the controls throughout the study. Neoplasms and Nonneoplastic Lesions: Hyperplasia of the transitional epithelium of the urinary bladder was present in nearly all exposed male and female rats examined at the interim evaluations. A transitional cell carcinoma was first observed at the 3-month interim evaluation in a male rat that received 18,000 ppm. At the 6- and 9-month interim evaluations, transitional cell papillomas or carcinomas were observed in both exposed groups of male rats. Transitional cell carcinomas were observed at the 6-month interim evaluation in females receiving 18,000 ppm and at the 9-month interim evaluation in females receiving 6,000 and 18,000 ppm. Adenomatous polyps of the large intestine were observed in a small number of exposed rats at the 6-, 9-, and 15-month interim evaluations. At the end of the study, the incidence of adenomatous polyps of the large intestine was significantly increased in all exposed groups and carcinomas of the large intestine were present in four males and two females from the 18,000 ppm groups. The incidence of hyperplasia of the transitional epithelium of the kidney pelvis was significantly increased in exposed male and female rats and transitional cell papillomas were present in three males and one female that received 18,000 ppm. Transitional cell carcinomas of the kidney were present in one male receiving 6,000 ppm and six males and one female receiving 18,000 ppm. Transitional cell carcinomas of the urinary bladder were seen in nearly all exposed male and female rats. Of the males and females receiving 6,000 ppm which were without carcinomas, three males and one female had transitional cell papillomas. Generalized centrilobular hypertrophy, focal hepatocellular necrosis, multifocal hepatocellular cytoplasmic vacuolation, and Kupffer cell pigmentation were observed in the livers of male and female rats at the 3- and 6-month interim evaluations; however, only Kupffer cell pigmentation was observed at the end of the study. Congestion of the red pulp of the spleen was observed in nearly all exposed male and female rats at the 3-, 6-, and 9-month interim evaluations but the incidence was only slightly increased in the 18,000 ppm groups at the end of the study. Degeneration and atrophy of the seminiferous tubule epithelium of the testes were observed at the 3- and 6-month interim evaluations in all male rats receiving 18,000 ppm. GENETIC TOXICOLOGY: o-Nitroanisole was tested in two laboratories for mutagenicity in Salmonella typhimurium strains TA97, TA98, TA100, TA1535, and TA1537 with and without exogenous metabolic activation (S9). Positive responses were observed at both laboratories in TA100 with and without S9 activation. One laboratory found no increase in mutations, while the second laboratory detected a weakly positive response in TA1535 without S9. No mutagenic activity was observed in the other tester strains. o-Nitroanisole was positive in the mouse lymphoma assay for induction of trifluorothymidine resistance in L5178Y cells without S9 activation. In cytogenetic tests with Chinese hamster ovary cells, o-nitroanisole induced a significant increase in chromosomal aberrations at the highest dose tested in the presence of S9 activation; sister chromatid exchanges were induced both with and without S9. CONCLUSIONS: Under the conditions of these feed studies there was clear evidence of carcinogenic activity of o-nitroanisole in male and female F344 rats that received diets containing 6,000 or 18,000 ppm for 6 months based on overall increased incidences of benign and malignant neoplasms of the urinary bladder, transitional cell neoplasms of the kidney, and benign and malignant neoplasms of the large intestine. There was a chemical-related increased incidence of mononuclear cell leukemia in male and female rats receiving diets containing 222, 666, or 2,000 ppm o-nitroanisole for 2 years. Marginally increased incidences of uncommon renal tubule neoplasms in male rats and forestomach neoplasms in male and female rats were considered uncertain findings. There was clear evidence of carcinogenic activity of o-nitroanisole in male B6C3F1 mice based on increased incidences of benign and malignant hepatocellular neoplasms. There was some evidence of carcinogenic activity of o-nitroanisole in female B6C3F1 mice based on increased incidences of hepatocellular adenomas. Increased severity of nephropathy in male rats, and increased incidences of focal hyperplasia of the renal tubule epithelium and forestomach ulcers in male rats, and of transitional cell hyperplasia of the urinary bladder, focal hyperplasia of the forestomach, and hyperplasia of transitional epithelium of the kidney pelvis in male and female rats were associated with exposure to o-nitroanisole. Synonyms: Methoxynitrobenzene, nitrophenyl methyl ether
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PMID:NTP Toxicology and Carcinogenesis Studies of o-Nitroanisole (CAS No. 91-23-6) in F344 Rats and B6C3F1 Mice (Feed Studies). 1261 95

The antithyroid acting drug propylthiouracil (PTU) was administered to male and female Wistar rats at 0, 0.1, 1, or 10mg/kg body weight for 4 weeks according to the draft protocol of the "Enhanced OECD Test Guideline 407" (enhanced TG 407) in order to investigate its suitability to detect endocrine-mediated effects. The study was conducted with two identical subsets of five animals per sex and dose each to provide data on sensitivity. The modified protocol includes the investigation of additional organ weights, pathology, and histopathology, of thyroid hormones, of spermatozoa, and of estrus cycle. At time of sacrifice, all females were in the diestrus stage as prescribed. Adverse effects were observed in the thyroid gland (hypertrophy/ hyperplasia) and the pituitary gland (hyperplasia of basophilic cells, hypoplasia of acidophilic cells) together with dose-related decreased serum triiodothyronine (T3) and thyroxine (T4) levels and increased thyroid stimulating hormone (TSH) levels. Other effects of PTU included decrease of organ weights, anaemia, impaired blood coagulation, and reduced activity of enzymes. Hence, some of the additional examined endpoints of the enhanced TG 407, e.g., examination of pituitary gland and thyroid hormones, were suitable to detect endocrine-modulating effects of propylthiouracil. Treatment of five animals provides sufficient sensitivity to detect the described adverse effects of propylthiouracil. The enhanced TG is currently under investigation in several laboratories, evaluation of all the results will allow determining its practicability as well as the most suitable additional endpoints.
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PMID:Detection of endocrine-modulating effects of the antithyroid acting drug 6-propyl-2-thiouracil in rats, based on the "Enhanced OECD Test Guideline 407". 1462 86

The effect of Trypanosomiasis on concentrations of plasma steroids and semen characteristics was studied in 24 dromedary bulls. Based upon the parasitological and serological diagnosis, 18 bulls were found infected with Trypanosoma evansi (Group 2) and six were found to be free from infection and served as controls (Group 1). The infected animals exhibited signs of anaemia indicated by the decrease of packed cell volume (PCV) and haemoglobin concentration (Hb), pale mucus membranes, weight loss, lethargy, weakness and dullness. However, five animals (27.8%) of the infected group revealed elevated rectal temperatures and three animals (16.7%) revealed testicular degeneration upon palpation of their scrotal contents. Concentrations of plasma oestradiol-17beta (86.5 +/- 8.6 pg/ml versus 232.5 +/- 74.4 pg/ml) and testosterone (4.8 +/- 0.7 ng/ml versus 2.7 +/- 1.5 ng/ml) were significantly different (P < 0.05) between the control and infected bulls. Evaluation of the semen collected by electroejaculation and evaluated by a computerized cell motion analyzer revealed normal semen characteristics in the control animals compared to deteriorated ones in the infected bulls. There were highly significant (P < 0.01) decreases in sperm count (12.2 +/- 1.3/ml versus 6.5 +/- 4.9 x 10(6)/ml), motility percentage (68.2 +/- 6.7% versus 27.4 +/-15.6%), percentage of live spermatozoa (73.2 +/- 8.3% versus 35.8 +/- 8.2%) and increases in percentage of morphological abnormalities (3.3 +/- 0.6% versus 15.9 +/- 1.0%) in the infected group. An examination of the plasma hormonal profiles and semen characteristics in the infected bulls indicated that altered Sertoli cell function due to formation of immune complexes in four bulls (Group 2A), pituitary dysfunction in six bulls (Group 2B), testicular degeneration in three bulls (Group 2C) and finally trypanotolerancy in five bulls (Group 2D) are possible factors responsible for poor semen characteristics and infertility induced by T. evansi infection in dromedary bulls.
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PMID:Trypanosomiasis-induced infertility in dromedary (Camelus dromedarius) bulls: changes in plasma steroids concentration and semen characteristics. 1530 88

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