Toxicity report series最新文献

{"title":"NTP technical report on the toxicity studies of Cupric Sulfate (CAS No. 7758-99-8) Administered in Drinking Water and Feed to F344/N Rats and B6C3F1 Mice.","authors":"Charles Hebert","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Cupric sulfate is an inorganic salt which is widely used in industry, agriculture, and veterinary medicine. Its applications include use as an algicide in potable waters and as a feed additive and therapeutic agent in swine, sheep, and cattle. Because copper salts are found in human water supplies, toxicity studies of cupric sulfate pentahydrate were conducted in male and female F344/N rats and B6C3F1 mice by the drinking water (2-week studies only) and dosed feed routes (2-week and 13-week studies). Animals were evaluated for hematology, clinical chemistry, urinalysis, reproductive toxicity, tissue metal accumulation, and histopathology. In the 2-week drinking water studies, groups of five rats and five mice per sex received cupric sulfate at concentrations of 300 to 30,000 ppm for 15 days. One female rat, one male mouse, and three female mice in the 3000 ppm groups and all rats and mice in the 10,000 and 30,000 ppm groups died before the end of the studies. The remaining mice and rats in the 3000 ppm groups gained little or lost weight. Water consumption in the three highest dose groups of both species was reduced by more than 65%. Clinical signs observed in these groups were typical of those seen in moribund animals and were attributed to dehydration. The only gross or microscopic change specifically related to cupric sulfate toxicity was an increase in the size and number of cytoplasmic protein droplets in the epithelium of the renal proximal convoluted tubule in male rats from the 300 and 1000-ppm groups. In the 2-week feed studies, groups of five rats and five mice per sex were fed diets containing 1000 to 16,000 ppm cupric sulfate. No chemical-related deaths occurred in any dose group. Compared to the controls, rats and mice in the two highest dose groups had reduced body weight gains which were attributed to decreased feed consumption. Hyperplasia with hyperkeratosis of the squamous epithelium on the limiting ridge of the forestomach was seen in rats and mice of each sex; this lesion was more severe in rats than in mice. Inflammation of the liver, periportal to midzonal in distribution, occurred in rats in the 8000 and 16,000 ppm groups. Depletion of hematopoietic cells was evident in rats of each sex in the bone marrow (8000 and 16,000 ppm) and spleen (16,000 ppm). Kidneys of male and female rats in the 4000, 8000, and 16,000 ppm groups had an increased number and size of protein droplets in the epithelia of the renal cortical tubules. In the 13-week feed studies, groups of 10 rats per sex received diets containing 500 to 8000 ppm cupric sulfate, and groups of 10 mice per sex received diets containing 1000 to 16,000 ppm cupric sulfate for 92 days; estimates of cupric sulfate consumption ranged from 32 to 551 mg/kg per day for rats and 173 to 4157 mg/kg per day for mice. There were no chemical-related deaths in rats or mice, and no clinical signs of cupric sulfate toxicity were recorded. Final mean body weights were lower than those","PeriodicalId":23116,"journal":{"name":"Toxicity report series","volume":"29 ","pages":"1-D3"},"PeriodicalIF":0.0,"publicationDate":"1993-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21971458","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 Glutaraldehyde (CAS No. 111-30-8) Adminstered by Inhalation to F344/N Rats and B6C3F1 Mice.","authors":"Frank Kari","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Glutaraldehyde is a potent sensory irritant with the capability to cross-link, or fix, proteins. It is used industrially as an antimicrobial agent and as a cold sterilant in hospitals, and it has a variety of other industrial uses. The toxicity of glutaraldehyde was evaluated in 2-week and 13-week inhalation exposure studies in F344/N rats and B6C3F1 mice. In addition to histopathology, evaluations included clinical pathology and assessments of sperm morphology and estrous cycle length. In vitro genetic toxicity studies included assessments of mutagenicity in Salmonella typhimurium and in mouse lymphoma L5178Y cells and analysis of chromosomal aberrations and sister chromatid exchanges in Chinese hamster ovary cells. The ability of glutaraldehyde to induce sex-linked recessive lethal mutations was also studied in vivo in Drosophila melanogaster. In 2-week inhalation studies, groups of five rats and five mice of each sex were exposed to glutaraldehyde by whole-body inhalation at concentrations of 0, 0.16, 0.5, 1.6, 5, and 16 ppm for 6 hours per day, 5 days per week. All rats and mice exposed to 5 or 16 ppm glutaraldehyde died before the end of the studies; all mice exposed to 1.6 ppm also died. Rats exposed to 1.6 ppm did not gain weight. Deaths were attributed to severe respiratory distress. Mice appeared to be more sensitive than rats because the small airways of the nasal passage of mice were more easily blocked by cell debris and keratin. Lesions noted in the nasal passage and larynx of rats and mice included necrosis, inflammation, and squamous metaplasia. At higher exposure concentrations, similar lesions were present in the trachea of rats and mice and in the lung and on the tongue of rats. In 13-week studies, groups of 10 rats and 10 mice of each sex were exposed to glutaraldehyde by whole-body inhalation at concentrations of 0, 62.5, 125, 250, 500, and 1000 ppb for 6 hours per day, 5 days per week. There were no exposure-related deaths in rats, but all mice exposed to 1000 ppb and two female mice exposed to 500 ppb died before the end of the study. Body weight gains were reduced in male rats exposed to 1000 ppb and in female rats exposed to 500 or 1000 ppb. Body weight gains of male mice exposed to 125, 250, or 500 ppb and female mice exposed to 250 or 500 ppb were reduced in a concentration-related manner. There was no clear evidence of systemic toxicity in rats or mice by histopathologic or clinical pathology assessments; however, exposure-related lesions in the respiratory tract were observed, and resembled those noted in the 2-week studies. In rats, the most severe lesions occurred in the anterior portions of the nasal passages and involved both the respiratory and olfactory epithelium. Hyperplasia and squamous metaplasia were most commonly noted on the lateral wall of the nasal cavity and on the tips of the nasoturbinates. Lesions were most extensive in rats exposed to 1000 ppb, but were also noted in the 250 and 500 ppb groups","PeriodicalId":23116,"journal":{"name":"Toxicity report series","volume":"25 ","pages":"1-E10"},"PeriodicalIF":0.0,"publicationDate":"1993-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21971444","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 1,6-Hexanediamine Dihydrochloride (CAS No. 6055-52-3) Administered by Drinking Water and Inhalation to F344/N Rats and B6C3F1 Mice.","authors":"Charles Hebert","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>1,6-Hexanediamine (HDA) is an aliphatic amine that is produced in large volumes in the United States. HDA is widely used as a corrosion inhibitor in lubricants and as an intermediate in the industrial synthesis of paints, resins, inks, and textiles. Toxicity studies of the dihydrochloride salt of HDA (HDDC) were conducted in male and female Fischer 344/N rats and B6C3F1 mice by the drinking water (2-week studies only) and whole-body inhalation routes (2-week and 13-week studies). Animals were evaluated for histopathology, clinical chemistry, hematology, and reproductive toxicity. In addition, the genetic toxicity of HDA was assessed in Salmonella typhimurium and in Chinese hamster ovary cells in vitro; HDDC was evaluated in the mouse micronucleus assay in vivo. In the 2-week drinking water studies, groups of 5 rats of each sex received HDDC at doses of 0.75 to 6.7 mg/mL, and groups of 5 mice of each sex received doses of 0.2 to 3.0 mg/mL for 14 or 15 days. All animals survived to the end of the studies. No gross or microscopic pathologic changes and no clinical abnormalities related to HDDC consumption were seen in any dose group. The only statistically significant change was a slight decrease in absolute and/or relative liver weights of female rats in the 1.7, 5.0, and 6.7-mg/mL treatment groups, in male rats in the 3.0 mg/mL treatment group, and in female mice in the 0.8 mg/mL treatment group. Because there was no significant toxicity in these studies, 13-week drinking water studies were not conducted. In the 2-week inhalation studies, 5 rats and 5 mice of each sex were exposed to 0, 10, 30, 89, 267, or 800 mg HDDC/m(3) for 6-hours per day for 12 days. In the highest exposure group (800 mg/m(3)), all male and female rats, all female mice, and 2 male mice died before the end of the studies. In the remaining groups, there was a dose-dependent depression in body weight gain in male and female mice, but not in rats. Clinical signs were primarily related to upper respiratory tract irritation and included dyspnea and nasal discharge in rats and mice. Absolute and relative liver weights were reduced in some male mice, but this did not occur in a dose- dependent manner. In rats, histopathologic lesions that were considered related to chemical exposure included inflammation and necrosis of laryngeal epithelium as well as focal inflammation and ulceration of the respiratory and olfactory nasal mucosa. In mice, focal areas of inflammation and necrosis were present in the respiratory mucosa of the larynx and trachea in the 2 highest exposure groups. Nasal lesions, including focal inflammation and ulceration, and degeneration and necrosis of the olfactory and respiratory epithelium were also seen in mice. In addition, mild testicular degeneration was present in 2 mice from the highest exposure group (800 mg/m(3)). In the 13-week inhalation studies, 10 rats and 10 mice of each sex were exposed to 0, 1.6, 5, 16, 50, or 160 mg HDDC/m(3) for 6 hours per d","PeriodicalId":23116,"journal":{"name":"Toxicity report series","volume":"24 ","pages":"1-D8"},"PeriodicalIF":0.0,"publicationDate":"1993-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21971445","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 Methyl Ethyl Ketone Peroxide (CAS No. 1338-23-4) in Dimethyl Phthalate (CAS No. 131-11-3) (45:55) Administered Topically in F344/N Rats and B6C3F1 Mice.","authors":"Errol Zeiger","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Methyl ethyl ketone peroxide (MEKP) is an unstable organic peroxide used in the manufacture of acrylic resins, as a hardening agent for fiberglass-reinforced plastics, and as a curing agent for unsaturated polyester resins. It is commercially available as a 40% to 60% solution in dimethyl phthalate (DMP). Because exposure to MEKP is typically through dermal contact, 2-week and 13-week toxicity studies were conducted by topical application of MEKP in DMP (45:55 w/w) to the clipped dorsal region of male and female Fischer 344/N rats and mice. Animals were evaluated for histopathology and for reproductive endpoints. In vitro genetic toxicity studies of MEKP included assessments of mutagenicity in Salmonella typhimurium and in mouse lymphoma L5178Y cells and analysis of chromosomal aberrations and sister chromatid exchanges in Chinese hamster ovary cells. In addition, the peripheral blood of mice from the 13-week study was evaluated in the micronucleus assay. In the 2-week studies, groups of 5 animals of each species and sex were administered MEKP in DMP for 5 days per week at doses of 50.6, 101.3, 202.5, 405, and 810 mg/kg body weight per day for rats and 112.5, 225, 450, 900, and 1800 mg/kg body weight per day for mice. Control groups received DMP or no treatment. No rats died during the studies, but at least 1 mouse in each group receiving MEKP died. Body weight gains of rats decreased with increasing doses of MEKP; body weight gains of mice were not affected by treatment. The primary effects of topical administration of MEKP in both rats and mice were an extensive coagulative necrosis of the epidermis and dermis, variable degrees of inflammation of the adnexa, and epidermal regeneration and hyperplasia at the application site. Lesions considered secondary to the dermal lesions included increased hematopoiesis in the spleen in rats and mice and increased myeloid hyperplasia of the bone marrow in mice, primarily at the higher doses. Mice showed a marked, dose-related increase in liver weight. In the 13-week dermal studies, groups of 10 rats and 10 mice of each sex were administered MEKP in DMP for 5 days per week at doses of 1.07, 3.57, 10.7, 35.7, and 107 mg/rat and 0.357, 1.19, 3.57, 11.9, and 35.7 mg/mouse. All high-dose mice, 3 high-dose female rats, and 1 female mouse in the 11.9 mg/animal group died or were sacrificed during the first week of the studies. Skin lesions similar to those seen in the 2-week studies were judged of sufficient severity to warrant early termination of surviving rats and mice in the 2 highest dose groups. All rats and mice in the remaining dose groups survived to the end of the studies, and weight gains were generally lower with increasing doses of MEKP. Skin lesions at the application site for the remaining animals (rats and mice) in the 10.7 mg/rat and 3.57 mg/mouse dose groups involved a spectrum of necrosis, inflammation, and acanthosis (epidermal hyperplasia). Lesions in the lower dose groups were limited t","PeriodicalId":23116,"journal":{"name":"Toxicity report series","volume":"18 ","pages":"1-C10"},"PeriodicalIF":0.0,"publicationDate":"1993-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21971519","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 Tetrachlorophthalic Anhydride (CAS No. 117-08-8) Administered by Gavage to F344/N Rats and B6C3F1 Mice.","authors":"Joel Mahler","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Tetrachlorophthalic anhydride (TCPA) is primarily used as a flame retardant in plastics. Toxicology studies were conducted by administering TCPA by oral gavage to F344/N rats and B6C3F1 mice for 13 weeks. Evaluations included histopathology, clinical pathology, and analyses of reproductive system parameters. The genetic toxicity of TCPA was assessed with in vitro tests of mutagenicity in Salmonella typhimurium and induction of sister chromatid exchanges and chromosomal aberrations in Chinese hamster ovary cells; sister chromatid exchanges and chromosomal aberrations were also determined in mouse bone marrow cells following in vivo exposure. The ability of TCPA to induce sex-linked recessive lethal mutations was also studied in vivo in Drosophila melanogaster. Groups of 10 rats and 10 mice of each sex received TCPA in corn oil vehicle by oral gavage (5 days/week) at doses of 0, 94, 187, 375, 750, and 1500 mg/kg. The deaths of 5 male rats and 1 female rat in the 1500 mg/kg dose group and 1 female rat in the 750 mg/kg dose group were considered due to chemical toxicity. Mean final body weights and body weight gains were depressed in male rats in the 375, 750, and 1500 mg/kg groups and in all groups of female rats receiving TCPA. Relative liver weights were slightly increased in males and females at doses of 187 mg/kg and higher, although a dose relationship was not apparent. Heart weights of surviving male rats in the high-dose group were also increased. Male and female rats exhibited dose-dependent increases in kidney weights and in the incidence and severity of renal tubule necrosis and/or dilation. No clinical pathology changes were clearly associated with chemical exposure. There were no chemical-related effects on survival, body weights, or organ weights in dosed mice. No chemical-related lesions were identified in organs examined microscopically. Decreases in red blood cell parameters consistent with a mild, poorly regenerative anemia were the only evidence of possible compound toxicity in dosed mice. Sperm morphology and vaginal cytology evaluations in rats and mice revealed no adverse changes related to TCPA exposure. In genetic toxicology studies, TCPA, tested with and without exogenous metabolic activation (S9), was not mutagenic in Salmonella typhimurium and did not induce sister chromatid exchanges or chromosomal aberrations in Chinese hamster ovary cells. In the Drosophila melanogaster sex-linked recessive lethal test, TCPA gave equivocal results when administered by feeding and negative results when administered by injection. No induction of chromosomal aberrations was observed in bone marrow cells of mice 17 hours after intraperitoneal injection of TCPA, although an increase in sister chromatid exchanges was detected in these cells 23 hours after injection. In summary, clear evidence of organ toxicity following administration of TCPA in corn oil by gavage for 13 weeks was limited to the kidney of rats. The no-observed-adverse-ef","PeriodicalId":23116,"journal":{"name":"Toxicity report series","volume":"28 ","pages":"1-D10"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21971441","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 ortho-, meta-, and para- Nitrotoluenes (CAS Nos. 88-72-2, 99-08-1, 99-99-0) Administered in Dosed Feed to F344/N Rats And B6C3F1 Mice.","authors":"J Dunnick","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Nitrotoluenes are high production volume chemicals used in the synthesis of agricultural and rubber chemicals and in various dyes. Because of differences in the metabolism of the 3 isomers and their capability to bind to DNA, comparative toxicity studies of o-, m-, or p-nitrotoluene were conducted in F344 rats and B6C3F1 mice. Animals were evaluated for histopathology, clinical pathology, and toxicity to the reproductive system. The nitrotoluenes were also studied in several in vitro and in vivo assays for genetic toxicity. In 14-day studies, o-nitrotoluene, m-nitrotoluene, or p-nitrotoluene was administered in the feed to male and female rats and mice at concentrations ranging from 388 to 20000 ppm (5 animals/chemical/species/sex/dose). There were no effects on survival or clinical signs of toxicity in these studies, although animals at the higher doses showed decreases in body weight gains relative to controls. In the 13-week studies, o-, m-, or p-nitrotoluene was given to male and female rats and mice (10 animals/chemical/species/ sex/dose) in the feed at concentrations between 625 and 10000 ppm. The estimated daily doses based on measures of feed consumption were 40 to 900 mg nitrotoluene/kg body weight/day for rats and 100 to 2000 mg/kg/day for mice and were similar for each of the 3 isomers when compared for each dietary level/sex/species. There were no effects on survival in any of the studies, and clinical signs of toxicity were limited to decreases in feed consumption. Decreased body weight gains occurred in dosed rats and mice in all studies at the higher dose levels and were most pronounced in rats receiving o-nitrotoluene. In rats, histopathologic analyses after 13 weeks of dosing showed toxicity to kidney, spleen, and testis in animals receiving any of the 3 isomers, and toxicity to the liver and mesothelium in male rats given o-nitrotoluene. Kidney toxicity observed in male rats was characterized by the presence of hyaline droplets in tubular epithelial cells, attributed to an increase in the level of alpha-2μ-globulin. Pigment, possibly lipofuscin, and karyomegaly in the p-nitrotoluene study were present in the renal tubular epithelium of dosed male and female rats. In the spleen of treated male and female rats, there was a mild increase in hematopoiesis, hemosiderin deposition, and/or congestion; this effect was most severe with the para-isomer, followed by the ortho- and then the meta-isomer. Administration of o-, m-, or p-nitrotoluene impaired testicular function of the rat, shown by degeneration of the testis and reduction in sperm concentration, motility, and spermatid number. All 3 isomers increased the length of the estrous cycle in rats. Hepatic toxicity was characterized by cytoplasmic vacuolization and oval cell hyperplasia and by an increase in the level of serum bile acids, SDH, and ALT activities in male rats given o-nitrotoluene. There was no histopathologic evidence for liver toxicity in male or female rats wit","PeriodicalId":23116,"journal":{"name":"Toxicity report series","volume":"23 ","pages":"1-E4"},"PeriodicalIF":0.0,"publicationDate":"1992-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21971446","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 N,N-Dimethylformamide (CAS No. 68-12-2) Administered by Inhalation to F344/N Rats and B6C3F1 Mice.","authors":"Dennis Lynch","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>N,N-Dimethylformamide (DMF), a colorless liquid with a high boiling point, is a solvent used in a large number of industrial processes. Male and female F344/N rats (30/sex/group) and B6C3F1 mice (10/sex/group) were exposed to DMF vapors at concentrations of 0, 50, 100, 200, 400, or 800 ppm, 6 hours/day, 5 days/week, for 13 weeks in whole body exposure inhalation studies. In addition to histopathology, sperm morphology, and vaginal cytology, which were evaluated in both species, the studies examined clinical pathology, cardiovascular, and renal function in rats only. In genetic toxicity studies, DMF was not mutagenic in Salmonella typhimurium strains TA100, TA1535, TA1537, or TA98, with or without S9 activation, nor did it induce germ cell mutations in male Drosophila melanogaster treated by feeding or injection. No induction of sister chromatid exchanges or chromosomal aberrations was noted in cultured Chinese hamster ovary cells treated in vitro with DMF, with or without an S9 metabolic activation system. In one laboratory, a marginal increase in mutant colonies was observed after treatment of mouse lymphoma L5178Y/TK+/- cells with DMF in the absence of S9; results from studies in 2 other laboratories were negative. In the 13-week studies, all rats survived exposures to DMF. Body weight gains were reduced by 50-65% in rats exposed at 800 ppm and to a lesser extent in the 400 ppm group. Evidence of hepatocellular injury was noted as early as day 4, based on increases in activities of liver-specific enzymes in serum in rats of both sexes exposed at 200-800 ppm. Serum cholesterol levels were increased at all exposure concentrations. Relative liver weights were increased in male rats exposed at 100 ppm and higher concentrations, and in female rats at all concentrations. Minimal to moderate centrilobular hepatocellular necrosis was seen in rats of both sexes exposed at 400 and 800 ppm; the lesion was more severe in females. There were no clear, adverse effects seen in urinalyses, in electrocardiographic studies, or in male reproductive system evaluations that could be related to DMF exposure. Hematologic studies showed mild hemoconcentration in males and females. Prolonged diestrus was observed in females exposed at 800 ppm. Among mice exposed to DMF for 13 weeks, there was no chemically related mortality. Body weight gains were approximately 30% less than controls in females exposed at 800 ppm. Relative liver weights were increased in males and females at all exposure concentrations. Centrilobular hepatocellular hypertrophy (minimal to mild) was found in all groups of male mice exposed to DMF, and in female mice exposed at 100 ppm and higher concentrations. The length of the estrous cycle in mice increased with increasing DMF exposure. In summary, DMF-related effects were seen in the liver of both rats and mice, with rats being more severely affected. For rats of both sexes, the no-observed-adverse-effect level (NOAEL) was 200 ppm, based on th","PeriodicalId":23116,"journal":{"name":"Toxicity report series","volume":"22 ","pages":"1-D20"},"PeriodicalIF":0.0,"publicationDate":"1992-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21971447","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-Hydroxy-4-methoxybenzophenone (CAS No. 131-57-7) Adminstered Topically and in Dosed Feed to F344/N Rats and B6C3F1 Mice.","authors":"J.E. French","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>2-Hydroxy-4-methoxybenzophenone (HMB) occurs naturally in flower pigments and is synthesized for use in sunscreens, as a UV stabilizer in various cosmetic products, and in plastic surface coatings and polymers. Toxicity studies of HMB were performed in F344/N rats and B6C3F1 mice, by administering HMB in feed and by topical application, in studies of 2 weeks' (5 animals/sex, dose and species) and 13 weeks' (10 animals/sex, dose and species) duration. Assessments included hematology, clinical chemistry, urinalysis, reproductive toxicity, and histopathologic evaluations. In both 2- and 13-week dosed feed studies, rats received diets containing 0, 3125, 6250, 12500, 25000, or 50000 ppm HMB. One high-dose female rat died during the 2-week study. Body weight gains of high-dose male and female rats were reduced in the 13-week study. Liver and kidney weights were increased in dosed rats in both studies. In the 2-week studies, enlarged livers were associated with a marked hepatocyte cytoplasmic vacuolization in rats receiving diets containing concentrations of 6250 ppm HMB or higher; renal lesions, consisting of dilated tubules and regeneration of tubular epithelial cells, were found primarily in high-dose rats. In the 13-week studies, kidney lesions progressed to include papillary degeneration, or necrosis, and inflammation, while the liver lesion appeared to regress; liver enzymes in serum remained elevated. Rats receiving a diet with 50000 ppm HMB showed markedly lower epididymal sperm density and an increase in the length of the estrous cycle at the end of the 13-week studies. In 2-week dermal studies, rats received topical applications of 1.25 to 20 mg of HMB in an acetone or lotion vehicle. The only effects noted were small and variable increases in liver and kidney weights, reaching statistical significance primarily in the higher dose groups. In 13-week studies, rats received topical doses from 12.5 to 200 mg/kg HMB in acetone. Kidney weights were elevated in dosed groups of female rats. No other findings were attributed to HMB treatment. In 2- and 13-week dosed feed studies, mice received feed containing 0, 3125, 6250, 12500, 25000, or 50000 ppm HMB. A dose- related increase in liver weight associated with hepatocyte cytoplasmic vacuolization was the only finding in mice in the 2- week studies. Decreased body weight gains were dose-related in mice in the 13-week studies; mild increases in liver weights were seen in dosed mice of both sexes. Kidney weights were increased variably in dosed females. Microscopic lesions were noted only in the kidneys of males receiving 50000 ppm HMB; these included eosinophilic protein casts in dilated renal tubules and a mild inflammation associated with the dilated tubules. Mice in the highest dose group exhibited a decrease in epididymal sperm density and an increase in length of the estrous cycle. In 2-week dermal studies, mice received topical applications from 0.5 to 8 mg HMB in an acetone or lotion vehi","PeriodicalId":23116,"journal":{"name":"Toxicity report series","volume":"21 ","pages":"1-E14"},"PeriodicalIF":0.0,"publicationDate":"1992-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21971448","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 Diethanolamine (CAS No. 111-42-2) Administered Topically and in Drinking Water to F344/N Rats and B6C3F1 Mice.","authors":"Ronald Melnick","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Diethanolamine is a high-production chemical used in cosmetics, in cutting fluids, as a dispersing agent for agricultural chemicals, and as an absorbent for acidic gases. Toxicology studies of diethanolamine were conducted in F344/N rats and B6C3F1 mice of both sexes for 2 weeks (5/sex/species/dose) and 13 weeks (10/sex/species/dose) to characterize and compare the effects of oral and dermal exposure. In addition to histopathology, evaluations included clinical pathology, urinalyses, and sperm morphology or vaginal cytology. In vitro genetic toxicity studies included assessments of mutagenicity in Salmonella typhimurium and mouse lymphoma L5178Y cells, analysis of chromosomal aberrations and sister chromatid exchange in Chinese hamster ovary cells, and determination of micronuclei formed in mice during the 13-week dermal exposure study. Groups of rats and mice received drinking water containing diethanolamine at concentrations of up to 10000 ppm during studies of 2 or 13 weeks duration. In the 2-week studies, rats and mice of both sexes received in the were 0, 630, 1250, 5000, and 10000 ppm diethanolamine in the drinking water. In the 13-week studies, rats received 0, 320, 630, 1250, 2500, and 5000 ppm (males) or 0, 160, 320, 630, 1250, and 2500 ppm (females) in drinking water; male and female mice received 0, 630, 1250, 2500, 5000, and 10000 ppm. All female rats in the 2 highest dose groups and 2 males in the 10000 ppm group in the 2-week study died before the end of the study. In the 13-week study, deaths of mice occurred in the 3 highest dose groups; 2 male rats in the top dose group also died. Surviving animals in the higher concentration groups in both studies exhibited depressed weight gains. Rats receiving diethanolamine developed a poorly regenerative, microcytic anemia in both studies. In the 2-week study, dosed male and female rats had increased kidney weights, renal tubular cell necrosis, and decreased renal function; rats in the 13-week study also showed increased incidences or severity of nephropathy, tubular necrosis, and mineralization. Degeneration of the seminiferous tubules of the testis was noted in dosed males in both the 2- and 13-week studies, and sperm motility and count were decreased in the 13-week study. Demyelination in the brain (medulla oblongata) and spinal cord was observed in male and female rats in the 13-week study. In mice, dose-dependent increases in liver weight were observed in males and females in the 2-week study; cytologic alteration and necrosis of individual hepatocytes were observed in the highest dose group. In the 13-week drinking water study in mice, nephropathy and tubular necrosis were observed in males, and degeneration of cardiac myocytes, and hepatocellular necrosis were seen in males and females. Cytologic alteration in the submandibular salivary gland was noted in male and female mice. Hepatocyte cytologic alteration also was noted in all dosed groups of mice. In the 2-week dermal studie","PeriodicalId":23116,"journal":{"name":"Toxicity report series","volume":"20 ","pages":"1-D10"},"PeriodicalIF":0.0,"publicationDate":"1992-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21971449","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 Black Newsprint Inks Administered Topically to F344/N Rats and C3H Mice.","authors":"Joel Mahler","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Toxicity studies were conducted by applying black newsprint inks or mineral oils to clipped skin of the dorsal interscapular area of C3H mice and F344/N rats of both sexes, to determine systemic and local effects. Four lots of both letterpress and offset types of newsprint ink were studied, either as composite mixtures or as individual lots. An industrial grade mineral oil, used as an extender for newsprint ink formulation, and USP medicinal grade mineral oil also were studied. Analyses for the presence of polycyclic aromatic hydrocarbons (PAHs) were conducted on composite ink mixtures and mineral oils; letterpress and offset ink mixtures were found to have cumulative concentrations of 206 and 105 ppm, respectively; the concentration of PAHs in the printing ink mineral oil sample was 208 ppm, while none were detected in the USP grade mineral oil. In genetic toxicity studies, letterpress and offset newsprint ink composite mixtures were each mutagenic in Salmonella typhimurium strains TA98 and TA100 when tested in a preincubation protocol with added hamster liver S9. With rat liver S9, results for both inks were positive in strain TA98 and negative in strain TA100. Neither type of ink was mutagenic in the absence of S9 activation. In 30-day studies, 5 rats and mice per sex were given single, daily dermal applications of letterpress or offset newsprint inks, 5 days per week, for a total of 21 - 22 applications. Dose groups for each type of ink received either the neat (undiluted) composite ink mixture, or the 3:1, 1:1, or 1:3 dilutions (ink:USP mineral oil), with a total dose volume of 100 (mice) or 250 (rats) &mgr;l. All animals survived until the end of the studies. Toxicity attributed to ink administration was limited to decreased body weight gains in female rats treated with neat and the 3:1 dilution of letterpress ink, and to scaliness at the site of application in 1 or more mice in each letterpress ink treatment group. As a result of grooming activity and the large amount of test chemical applied, chemicals were spread over the body, and there was evidence that some oral ingestion had occurred. In 13-week studies, various ink and mineral oil formulations were administered dermally to 10 rats and mice per sex. To prevent accumulation of inks and distribution over the body as seen in the 30-day studies, the frequency of application was reduced to twice weekly and the total dose volume was decreased to 20 microliters for mice and 50 microliters for rats. Treatment groups for rats consisted of letterpress ink mixture, offset ink mixture, printing ink mineral oil, USP mineral oil, and clipped, untreated controls. Groups of mice were administered each of the 4 individual lots of both letterpress and offset inks, the composite mixtures of each, and printing ink and USP mineral oils; clipped, untreated groups served as controls. All rats, all male mice, and all female mice except one administered offset ink-lot E survived to the end of the studi","PeriodicalId":23116,"journal":{"name":"Toxicity report series","volume":"17 ","pages":"1-E2"},"PeriodicalIF":0.0,"publicationDate":"1992-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21971520","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}