Toxicity report series最新文献

{"title":"NTP Technical Report on the metabolism, toxicity and predicted carcinogenicity of diazoaminobenzene (CAS No. 136-35-6).","authors":"Nancy B Ress","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Diazoaminobenzene is used as an intermediate, complexing agent, and polymer additive. It is also an impurity in certain color additives used in cosmetics, food products, and pharmaceuticals. Diazoaminobenzene was selected for metabolism and toxicity studies based on the potential for worker exposure from its use in laboratories, positive Salmonella typhimurium gene mutation data, its presence as an impurity in foods and cosmetics, and the lack of adequate toxicity data. Several structural analogues and presumed metabolites of diazoaminobenzene are carcinogenic, providing evidence for the possible carcinogenicity of diazoaminobenzene. The chemical structure of diazoaminobenzene suggested that it would be metabolized into aniline and benzene; therefore, metabolism and disposition studies were performed in male and female F344/N rats and male B6C3F1 mice administered a single oral, dermal, or intravenous dose of diazoaminobenzene. Electron spin resonance (ESR) studies were conducted to assess the possible formation of a phenyl radical from the reduction of diazoaminobenzene by components of the cytochrome P450 mixed-function oxidase (P450) system in microsomes or by gut microflora in anaerobic cecal incubations. Bile duct-cannulated male F344/N rats were administered diazoaminobenzene and 5,5-dimethyl-1- pyrroline-N-oxide (DMPO) for in vivo determination of the DMPO-phenyl radical. 16-Day toxicity studies were performed to identify target organs of diazoaminobenzene following dermal application to male and female F344/N rats and B6C3F1 mice. In the disposition and metabolism studies, oral doses of 20 mg/kg to male and female rats and male mice were readily absorbed and excreted mainly in the urine, with exhalation of volatile organics accounting for about 1% of the dose. The only volatile metabolite detected in the breath was benzene, and all the metabolites in the urine were those previously shown to result from the metabolism of benzene and aniline in rats and mice. While dermal doses to rats and mice (2 and 20 mg/cm2) were only slightly absorbed, benzene and aniline metabolites were nonetheless detected in the urine. High circulating levels of benzene, aniline, and their metabolites were detected in the blood of rats administered 20 mg/kg diazoaminobenzene as early as 15 minutes after exposure. At 24 hours after dosing, diazoaminobenzene was detected at low levels (<1%) in the adipose tissue, blood, kidney, liver, muscle, skin, and spleen. Metabolites of benzene and aniline were also formed in an in vitro study using human liver slices. In the ESR spin-trapping experiments, the ESR spectrum of the DMPO-phenyl radical was detected when diazoaminobenzene was incubated with microsomes or P450 reductase, DMPO, and NADPH, or when incubated with cecal contents and DMPO. The DMPO-phenyl radical spectrum was not attenuated by the P450 inhibitor, 1-aminobenzotriazole, or carbon monoxide suggesting that P450s were not required. In in vivo experiments","PeriodicalId":23116,"journal":{"name":"Toxicity report series","volume":" 73","pages":"1-23, A1-C6"},"PeriodicalIF":0.0,"publicationDate":"2002-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22057923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NTP technical report on the toxicity studies of 1-Nitropyrene (CAS No. 5522-43-0) Administered by Inhalation to F344/N Rats.","authors":"Po Chan","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>1-Nitropyrene is a by-product of combustion. It is the predominant nitrated polycyclic aromatic hydrocarbon emitted in diesel engine exhaust and has been found at concentrations of up to 57 pg/m(3) in the air over urban and suburban areas. 1-Nitropyrene is detoxified mainly to 1-aminopyrene by nitro reduction. 1-Nitropyrene can also undergo ring oxidation, depending on the concentration of oxygen. Aryl nitrenium ions generated by nitro reduction or K-region nitropyrene epoxides generated by ring oxidation can react with DNA, forming adducts. 1-Nitropyrene was nominated for toxicity study because it is mutagenic, it is found in the environment, and it has potential for human exposure. Administration by inhalation was chosen because humans are exposed to 1-nitropyrene mainly by inhalation. Nose-only inhalation was chosen because whole-body inhalation exposure would require a large quantity of purified 1-nitropyrene that is expensive and difficult to procure. The study was performed in rats because of technical problems with conducting nose-only inhalation studies in mice and because mice are known to be more resistant to 1-nitropyrene toxicity. In the base study, groups of 10 male and 10 female 7-week-old F344/N rats were exposed to 0, 0.5, 2, 8, 20, or 50 mg/m(3) 1-nitropyrene aerosol, 6 hours per day, 5 days per week, for 13 weeks. At 13 weeks, rats were evaluated for histopathology, clinical pathology, and reproductive system effects. In a supplemental evaluation, toxicokinetic effects were assessed in male F344/N rats exposed to 1-nitropyrene for 13 weeks. All rats survived to the end of the 13-week exposure. For all groups, body weight gains of exposed rats were similar to those of concurrent controls (but lower than those of historical whole body inhalation study control rats); however, liver weights of exposed male rats were higher than those of the controls. There were slight variations in certain hematology and clinical chemistry parameters for some groups, but these were not considered related to 1-nitropyrene exposure. Squamous metaplasia of the respiratory mucosa was observed in the larynx of male rats exposed to 1-nitropyrene at a concentration of 2 mg/m(3) or greater and of female rats at all exposure concentrations. Squamous metaplasia of the bronchial epithelium also occurred in male and female rats in the higher exposure groups. Cytoplasmic alteration of the nasal respiratory epithelium was observed in both sexes exposed to 1-nitropyrene at a concentration of 8 mg/m(3)or greater. No treatment-related effects on sperm motility or vaginal cytology were noted. However, testicular atrophy was observed in all male rats and was considered a secondary effect resulting from the daily confinement within the exposure tubes. The elimination half-life of 1-nitropyrene in the lungs was about 1 hour for rats exposed to 8 mg/m(3)and 6 hours for rats exposed to 50 mg/m(3). Lung burdens of 1-nitropyrene in rats exposed to 8 mg/m(3) remained t","PeriodicalId":23116,"journal":{"name":"Toxicity report series","volume":"34 ","pages":"1-D2"},"PeriodicalIF":0.0,"publicationDate":"1996-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21971453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"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.","authors":"Daniel Marsman","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>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 tes","PeriodicalId":23116,"journal":{"name":"Toxicity report series","volume":"30 ","pages":"1-G5"},"PeriodicalIF":0.0,"publicationDate":"1995-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21971457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NTP technical report on the toxicity studies of Isoprene (CAS No. 78-79-5) Administered by Inhalation to F344/N Rats and B6C3F1 Mice.","authors":"Ronald Melnick","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Isoprene, the 2-methyl analogue of 1,3-butadiene, has a high production volume and is used largely in the manufacture of synthetic rubber. Isoprene is also the major endogenous hydrocarbon exhaled in human breath. Two-week and 13-week inhalation toxicology studies were conducted in male and female F344/N rats and B6C3F1 mice to characterize potential adverse effects of isoprene. Male rats and male mice were also exposed to isoprene vapors for 6 months followed by a 6-month recovery period (stop- exposure protocol) to determine if isoprene produces a carcinogenic response similar to that of 1,3-butadiene after intermediate exposure durations. In addition to histopathology, evaluations included clinical pathology, tissue glutathione analyses, forelimb and hindlimb grip strength analyses, and sperm motility and vaginal cytology. Data from inhalation teratology studies of isoprene in rats and mice are also reported. In vitro genetic toxicity studies included assessments of mutagenicity in Salmonella typhimurium and sister chromatid exchanges and chromosomal aberrations in Chinese hamster ovary cells. In conjunction with the inhalation studies in mice, evaluations were also made of sister chromatid exchanges and chromosomal aberrations in bone marrow cells and micronuclei in peripheral blood of male mice exposed to isoprene for 12 days or 13 weeks. Target concentrations of isoprene in the inhalation chambers were 0, 438, 875, 1,750, 3,500, and 7,000 ppm in the 2-week studies; 0, 70, 220, 700, 2,200, and 7,000 ppm in the 13-week and stop-exposure studies; and 0, 280, 1,400, and 7,000 ppm in the teratology studies. In the 2-week studies, no changes related to chemical administration were observed in survival, body weight gain, clinical signs, hematologic or clinical chemistry parameters, or the incidence of gross or microscopic lesions in rats. In mice, there were no effects on survival; the mean body weight of males in the 7,000 ppm group was less than that of the controls. In mice, exposure to isoprene caused decreases in hematocrit values, hemoglobin concentrations, and erythrocyte counts, atrophy of the testis and thymus, cytoplasmic vacuolization of the liver, olfactory epithelial degeneration in the nasal cavity, and epithelial hyperplasia in the forestomach. Exposure to isoprene for 13 weeks produced no discernible toxicologic effects in rats. In the stop-exposure study, interstitial cell hyperplasia of the testis was observed in all male rats in the 7,000 ppm group after 6 months of exposure. Following the 6-month recovery period, male rats exposed to 700, 2,200, or 7,000 ppm isoprene had slightly greater incidences of interstitial cell adenomas of the testes than the controls. Exposure to isoprene for 13 weeks or 6 months produced no clear exposure-related effects on body weight gain in male or female mice; however, survival was decreased for male mice exposed to 7,000 ppm isoprene for 6 months. More notably, toxic and carcinogenic effect","PeriodicalId":23116,"journal":{"name":"Toxicity report series","volume":"31 ","pages":"1-G5"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21971456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NTP technical report on the toxicity studies of Methylene Bis(thiocyanate) (CAS No. 6317-18-6) Administered by Gavage to F344/N Rats and B6C3F1 Mice.","authors":"L.T. Burka","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Methylene bis(thiocyanate) is used as a biocide in a number of applications. Its major use is in water cooling systems and paper mills as an inhibitor of algae, fungi, and bacteria. Methylene bis(thiocyanate) was selected for study because of the potential for human exposure to the compound and because of the interest in organothiocyanates as a chemical class. Toxicity studies of methylene bis(thiocyanate) (approximately 98% pure) were conducted with male and female F344/N rats and B6C3F1 mice; the compound was administered to the animals by gavage in an aqueous methyl cellulose vehicle for 2 weeks or 13 weeks. In addition to these studies, the genetic toxicity of methylene bis(thiocyanate) was evaluated by determining mutagenicity in Salmonella typhimurium with and without S9 activation and frequency of micronucleated normochromatic erythrocytes in the peripheral blood of mice. In the 2-week studies, groups of five rats and five mice per sex were administered methylene bis(thiocyanate) at concentrations of 0, 10, 20, 40, 80, and 160 mg/kg body weight. All animals in the two highest dose groups (80 and 160 mg/kg) died by Day 2 of the studies. Except for one female rat, all animals receiving 40 mg/kg methylene bis(thiocyanate) also died before the end of the studies. Few significant gross lesions were observed in the 80 and 160 mg/kg groups. Clinical observations were similar to those reported for cyanide toxicity and included dyspnea, tremors. and ataxia. The stomach, which was identified as the target organ in rats and mice surviving for at least 24 hours, had necrotic inflammatory lesions of the mucosal surface of both the glandular and nonglandular portions. In the 13-week studies, groups of 10 rats and 10 mice per sex were administered methylene bis(thiocyanate) at concentrations of 0, 1, 2, 4, 8, and 16 mg/kg body weight. In the rat study, deaths occurred in the 2, 4, 8, and 16 mg/kg groups, while in the mouse study, deaths occurred only in the 8 and 16 mg/kg groups. As in the 2-week studies, the stomach was identified as the primary target organ. However, the lower doses administered in the 13-week studies resulted in gastric effects that were limited to the forestomach and consisted primarily of squamous mucosal hyperplasia and hyperkeratosis. Rats receiving the higher doses of methylene bis(thiocyanate) developed a mild anemia, and sperm motility was decreased in male rats receiving 4 or 8 mg/kg. Methylene bis(thiocyanate) was not mutagenic in S. typhimurium, with or without S9 activation. The frequencies of micronucleated normochromatic erythrocytes in the peripheral blood of dosed and control mice were similar. Chemical disposition studies of [14C]-labeled methylene bis(thiocyanate) were conducted in male F344 rats. In these studies, more than 90% of the administered radioactivity was eliminated in 48 hours. However, as the dose was increased from 0.2 to 1 to 10 mg/kg, greater percentages of the administered radioactivity remained","PeriodicalId":23116,"journal":{"name":"Toxicity report series","volume":"32 ","pages":"1-E7"},"PeriodicalIF":0.0,"publicationDate":"1993-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21971455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NTP technical report on the toxicity studies of Riddelliine (CAS No. 23246-96-0) Administered by Gavage to F344 Rats and B6C3F1 Mice.","authors":"Po Chan","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Riddelliine is a naturally occurring pyrrolizidine alkaloid, a class of compounds occurring in rangeland plants of the genera Crotalaria, Amsinckia, and Senecio. Two-week and 13-week rodent toxicity studies of riddelliine were conducted because riddelliine can be a contaminant of foodstuffs, such as meat, grains, seeds, milk, herbal tea, and honey. In addition to histopathology, evaluations included clinical pathology and reproductive toxicity. In vitro genetic toxicity studies included assessments of mutagenicity in Salmonella typhimurium and of the induction of chromosomal aberrations and sister chromatid exchanges in Chinese hamster ovary cells. Riddelliine was also evaluated in vivo for the induction of micronuclei in mouse bone marrow and in peripheral blood and for the induction of S-phase synthesis and unscheduled DNA synthesis in the liver of rats and mice. In the 2-week studies, groups of five male and five female F344/N rats and B6C3F1 mice were administered riddelliine in 0.1 M phosphate buffer by gavage at dose levels of 0, 0. 33, 1.0, 3.3, 10, or 25 mg/kg body weight five times per week, for a total of 12 doses. Four of five male rats in the 25 mg/kg group died or were killed moribund before the end of the study. Mean body weight gains of male rats in the 10 and 25 mg/kg groups were depressed. No deaths or body weight effects were observed in female rats. Male rats had dose-related hemorrhagic centrilobular hepatic necrosis, hepatocytic karyomegaly and cytologic alterations, pulmonary hemorrhage and/or edema, splenic extramedullary hematopoiesis, and pancreatic edema. Female rats exhibited fewer and less severe lesions than identically treated male rats. Heart weights of treated male and female rats were lower than those of the controls. No deaths or effects on body weight were observed in treated mice. Dose-related increases in absolute and relative liver weights and increased incidences of hepatic cytomegaly were the only treatment-related findings in male and female mice administered riddelliine. In the 13-week studies, groups of 20 male and 20 female F344/N rats and B6C3FI mice were administered riddelliine in 0.1 M phosphate buffer by gavage five times per week for 13 weeks. Rats received 0, 0.1, 0.33, 1.0, 3.3, or 10 mg/kg and mice received 0, 0.33, 1.0, 3.3, 10, or 25 mg/kg. Ten animals from each dose group were killed after 13 weeks of treatment. The remaining 10 animals in each dose group were observed without further treatment for up to 14 weeks; five animals from each dose group were killed after 7 weeks of recovery, and the remaining five animals per dose group were killed at the end of the 14-week recovery period. During the 13-week treatment period, 19 of 20 male rats in the high-dose group died; all others survived. Body weight gains were decreased with increasing dose at Week 13. During the 14-week recovery period, all male rats survived, but five high-dose females died. Mean body weight gains of dosed and contr","PeriodicalId":23116,"journal":{"name":"Toxicity report series","volume":"27 ","pages":"1-D9"},"PeriodicalIF":0.0,"publicationDate":"1993-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21971442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NTP technical report on the toxicity studies of a Chemical Mixture of 25 Groundwater Contaminants Administered in Drinking Water to F344/N Rats and B6C3F(1) Mice.","authors":"R. Yang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Toxicity studies were performed with a chemically defined mixture of 25 groundwater contaminants, using dose levels considered to have environmental relevance. The mixture contained 19 organic compounds and six metals (shown below); the selection of these compounds was based primarily on the frequency of their occurrence in United States Environmental Protection Agency surveys of groundwater contamination in the vicinity of hazardous waste disposal sites. This report focuses primarily on 26-week drinking water toxicity studies with male and female F344/N rats and B6C3F(1) mice. The endpoints evaluated included histopathology, clinical pathology, neurobehavioral studies, and reproductive toxicity. Additional studies using this same chemical mixture are briefly reviewed in this report and include an evaluation of spermatogenesis in B6C3F(1) mice exposed to the chemical mixture for 13 weeks, a continuous breeding study with Sprague-Dawley rats and CD-1(R) Swiss mice, studies of myelotoxicity in B6C3F(1) mice exposed to the chemical mixture for up to 31.5 weeks, studies of immunosuppression in B6C3F(1) mice exposed for up to 13 weeks, in vitro mutagenicity assays in Salmonella typhimurium and Escherichia coli, and measures of genetic damage in bone marrow and peripheral blood of F344/N rats and B6C3F(1) mice in 2-week drinking water studies. In a 26-week drinking water study in which rats were administered the chemical mixture at composite contaminant concentrations of 0, 11, 38, 113, or 378 ppm, no deaths occurred and the body weight gain of high-dose males was slightly less than that of the controls. Water consumption decreased with dose and was 24% to 28% less than that of the controls at the highest concentration. Changes in organ weights occurred primarily in high-dose rats and included increased absolute and relative liver and kidney weights in females, increased relative kidney weight in males, and decreased absolute and relative thymus weights in males and females. Hematologic assessments indicated that rats receiving 378 ppm developed a microcytic anemia consistent with that accompanying iron depletion. Multiple foci of inflammation occurred in the liver of exposed rats. In high-dose females, these liver lesions were especially prominent and included bile duct and oval cell hyperplasia. Inflammation also occurred in the mesenteric lymph nodes, the adrenal gland, and the spleen. The amount of hemosiderin in the spleens of rats receiving the higher concentrations of the chemical mixture was less than normal. Components of a chemical mixture of 25 groundwater contaminants include acetone, aroclor 1260, arsenic, benzene, cadmium, carbon tetrachloride, chlorobenzene, chloroform, chromium, 1,1-dichloroethane, 1,2-dichloroethane, 1,1-dichloroethylene, 1,2-trans-dichloroethylene, di(2-ethylhexyl) phthalate, ethylbenzene, lead, mercury, methylene chloride, nickel, phenol, tetrachloroethylene, toluene, 1,1,1-trichloroethane, trichloroethylene, x","PeriodicalId":23116,"journal":{"name":"Toxicity report series","volume":"35 ","pages":"1-I12"},"PeriodicalIF":0.0,"publicationDate":"1993-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21971452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NTP technical report on the toxicity studies of Pesticide/Fertilizer Mixtures Administered in Drinking Water to F344/N Rats and B6C3F1 Mice.","authors":"R. Yang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Toxicity studies were performed with pesticide and fertilizer mixtures representative of groundwater contamination found in California and Iowa. The California mixture was composed of aldicarb, atrazine, 1,2-dibromo-3-chloropropane, 1,2- dichloropropane, ethylene dibromide, simazine, and ammonium nitrate. The Iowa mixture contained alachlor, atrazine, cyanazine, metolachlor, metribuzin, and ammonium nitrate. The mixtures were administered in drinking water (with 512 ppm propylene glycol) to F344/N rats and B6C3F1 mice of each sex at concentrations ranging from 0.1x to 100x, where 1x represented the median concentrations of the individual chemicals found in studies of groundwater contamination from normal agricultural activities. This report focuses primarily on 26-week toxicity studies describing histopathology, clinical pathology, neurobehavior/neuropathology, and reproductive system effects. The genetic toxicity of the mixtures was assessed by determining the frequency of micronuclei in peripheral blood of mice and evaluating micronuclei and sister chromatid exchanges in splenocytes from female mice and male rats. Additional studies with these mixtures that are briefly reviewed in this report include teratology studies with Sprague-Dawley rats and continuous breeding studies with CD-1 Swiss mice. In 26-week drinking water studies of the California and the Iowa mixtures, all rats (10 per sex and group) survived to the end of the studies, and there were no significant effects on body weight gains. Water consumption was not affected by the pesticide/fertilizer contaminants, and there were no clinical signs of toxicity or neurobehavioral effects as measured by a functional observational battery, motor activity evaluations, thermal sensitivity evaluations, and startle response. There were no clear adverse effects noted in clinical pathology (including serum cholinesterase activity), organ weight, reproductive system, or histopathologic evaluations, although absolute and relative liver weights were marginally increased with increasing exposure concentration in both male and female rats consuming the Iowa mixture. In 26-week drinking water studies in mice, one male receiving the California mixture at 100x died during the study, and one control female and one female in the 100x group in the Iowa mixture study also died early. It could not be determined if the death of either of the mice in the 100x groups was related to consumption of the pesticide/fertilizer mixtures. Water consumption and body weight gains were not affected in these studies, and no signs of toxicity were noted in clinical observations or in neurobehavioral assessments. No clear adverse effects were noted in clinical pathology, reproductive system, organ weight, or histopathologic evaluations of exposed mice. The pesticide/fertilizer mixtures, when tested over a concentration range similar to that used in the 26-week studies, were found to have no effects in teratology studies o","PeriodicalId":23116,"journal":{"name":"Toxicity report series","volume":"36 ","pages":"1-G3"},"PeriodicalIF":0.0,"publicationDate":"1993-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21971451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NTP technical report on the toxicity studies of 2-Chloronitrobenzene (CAS No. 88-73-3) and 4-Chloronitrobenzene (CAS No. 100-00-5) Administered by Inhalation to F344/N Rats and B6C3F1 Mice.","authors":"John Bucher","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>2-Chloronitrobenzene and 4-chloronitrobenzene are oily yellow solids that are used primarily as chemical intermediates in the production of dyes, lumber preservatives, drugs, and photographic chemicals. Although these chemicals are solids at room temperature, the vapor pressures of these chemicals are sufficiently high to result in significant inhalation exposure. Toxicity studies of 2-chloronitrobenzene and 4-chloronitrobenzene were performed by exposing male and female F344/N rats and B6C3F1 mice to the chemicals by whole-body inhalation 6 hours per day, 5 days per week, for 2 weeks or 13 weeks. Animals were evaluated for histopathology, clinical chemistry (rats), hematology (rats), and reproductive system effects. In separate studies, the dermal absorption of the chemicals was compared, and the absorption, distribution, metabolism, and excretion were partially characterized following oral administration to male F344/N rats. 2-Chloronitrobenzene and 4-chloronitrobenzene were also administered orally to CD-1(R) Swiss mice for evaluation of reproductive and developmental toxicity. Genetic effects were evaluated in Salmonella typhimurium, in Chinese hamster ovary cells, and in Drosophila melanogaster. The highest exposure concentrations used in the 2 week and 13 week studies were limited by technical factors in vapor generation to 18 ppm (115.2 mg/m(3)) for 2-chloronitrobenzene and 24 ppm (153.6 mg/m(3)) for 4-chloronitrobenzene. Other concentrations were 0, 1.1, 2.3, 4.5, and 9 ppm (0, 7, 14.7, 28.8, and 57.6 mg/m(3)) for 2-chloronitrobenzene and 0, 1.5, 3, 6, and 12 ppm (0, 9.6, 19.2, 38.4, and 76.8 mg/m(3)) for 4-chloronitrobenzene. In 2-week studies with 2-chloronitrobenzene, all rats survived to the end of the study. One of five male mice exposed to 18 ppm died, but weight gains of exposed rats and mice were not affected. Exposed rats and mice had concentration-related increases in liver weights, and spleen weights were increased in rats and mice exposed to 18 ppm. Histopathologic findings in rats were limited to hemosiderin deposition in the liver and spleen at the highest exposure concentration. Exposed mice, primarily those in the 18 ppm groups, had coagulative necrosis, hepatocytomegaly, and granulomatous inflammation in the liver. Splenic changes including increased hematopoietic cell proliferation and hemosiderin deposition occurred at concentrations as low as 4.5 ppm. In 13-week studies with 2-chloronitrobenzene, all rats survived to the end of the study; 2 of 10 male mice exposed to 18 ppm died. Body weight gains of exposed rats and mice were similar to or somewhat higher than those of the respective controls. Methemoglobinemia occurred in rats and resulted in a normocytic, normochromic anemia that became responsive by the end of the study. Exposed rats and mice had increased liver weights, but these increases were not as great as those seen in the 2-week studies. Spleen weights were increased in exposed rats. Histopathologic ch","PeriodicalId":23116,"journal":{"name":"Toxicity report series","volume":"33 ","pages":"1-F25"},"PeriodicalIF":0.0,"publicationDate":"1993-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21971454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NTP technical report on the toxicity studies of Ethylene Glycol Ethers: 2-Methoxyethanol, 2-Ethoxyethanol, 2-Butoxyethanol (CAS Nos. 109-86-4, 110-80-5, 111-76-2) Administered in Drinking Water to F344/N Rats and B6C3F1 Mice.","authors":"M. Dieter","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Glycol alkyl ethers represent a class of high-production-volume chemicals with widespread industrial applications as solvents and chemical intermediates. Comparative toxicity studies with three glycol ethers, 2-methoxyethanol, 2-ethoxyethanol, and 2-butoxyethanol, were conducted in F344/N rats and B6C3F1 mice in both 2-week and 13-week drinking water studies. Toxicologic endpoints evaluated in animals included histopathology, hematology, clinical chemistry, urinalysis, and reproductive system parameters. Genetic toxicity was also evaluated for each glycol ether in several in vitro and in vivo assays. In the 2-week studies, groups of five male and five female rats and mice received 2-methoxyethanol, 2-ethoxyethanol, or 2-butoxyethanol in the drinking water. Estimates of compound consumption based on water consumption by male and female rats ranged from 100 to 400 mg/kg for 2-methoxyethanol, 200 to 1600 mg/kg for 2-ethoxyethanol, and 70 to 300 mg/kg for 2-butoxyethanol. For mice, consumption values ranged from 200 to 1300 mg/kg for 2-methoxyethanol, 400 to 2800 mg/kg for 2-ethoxyethanol, and 90 to 1400 mg/kg for 2-butoxyethanol. There were no chemical-related effects on survival for rats or mice in the 2-week studies. Decreased body weight gains were noted for both male and female rats treated with 2-methoxyethanol or 2-ethoxyethanol for 2 weeks, and there were dose-related decreases in water consumption for rats of each sex treated with the ethylene glycol ethers. Most of the changes in organ weights for rats and mice treated with the glycol ethers were sporadic (mice) or related to low final mean body weights (rats), except for thymic atrophy in male and female rats and testicular atrophy in males of both species receiving 2-methoxyethanol or 2-ethoxyethanol. In the 13-week studies in rats, groups of 10 males and 10 females received 2-methoxyethanol, 2-ethoxyethanol, or 2-butoxyethanol in the drinking water at concentrations ranging from 750 to 6000 ppm, 1250 to 20,000 ppm, or 750 to 6000 ppm, respectively. In the 13-week studies in mice, groups of 10 males and 10 females received 2-methoxyethanol, 2-ethoxyethanol, or 2-butoxyethanol in the drinking water at concentrations ranging from 2000 to 10,000 ppm, 2500 to 40,000 ppm, or 750 to 6000 ppm, respectively. Estimates of compound consumption based on water consumption by male and female rats ranged from 70 to 800 mg/kg for 2-methoxyethanol, 100 to 2200- mg/kg for 2-ethoxyethanol, and 70 to 500 mg/kg for 2-butoxyethanol. For-mice, consumption values ranged from 300 to 1800 mg/kg for 2-methoxyethanol, 600 to 11,000 mg/kg for 2-ethoxyethanol, and 100 to 1300 mg/kg for 2-butoxyethanol. Chemical-related mortality occurred in male and female rats administered 4500 or 6000 ppm 2-methoxyethanol and in male and female rats administered 20,000 ppm 2-ethoxyethanol. No deaths occurred in rats administered 2-butoxyethanol or in mice administered 2-methoxyethanol, 2-ethoxyethanol, or 2-butoxyethanol. Dec","PeriodicalId":23116,"journal":{"name":"Toxicity report series","volume":"26 ","pages":"1-G15"},"PeriodicalIF":0.0,"publicationDate":"1993-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21971443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}