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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serologically confirmed cases of dengue fever among Swedish tourists were studied retrospectively. Dengue fever was found to be the most commonly diagnosed imported arbovirus disease in Sweden during the period December 1989-November 1990. 24 cases were diagnosed. The geographical epidemiology showed that 17/23 who answered a questionnaire were infected in Thailand, most often during spring and early summer. 17 patients were admitted to hospital. All patients had high fever. Other common symptoms were myalgia, headache, fatigue/prostration and erythema. All patients but 1 with a long-standing ataxia recovered without sequelae. Low white blood cell and platelet counts were registered in all sampled patients. Depressed sodium levels and elevated liver enzymes were seen regularly. Dengue virus type 1 was isolated from 2 patients who suffered from dengue haemorrhagic fever grade II in the course of their primary dengue virus infection.
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PMID:Dengue fever among Swedish tourists. 805 9

A retrospective study was conducted of 40 loperamide poisoning cases recorded at the Centre National d'Informations Toxicologiques Veterinaires. An apparent breed susceptibility of Collie dogs was observed. Neurologic disturbances (ataxia and prostration) were significant clinical findings. Treatment with naloxone resulted in rapid reversal of signs without sequelae.
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PMID:Loperamide poisoning in the dog. 882 47

Felbamate, 2-phenyl-1,3-propanediol dicarbamate, is a novel anticonvulsant that is effective against both chemically and electrically induced seizures in laboratory animals. Acute, subchronic, and chronic studies were conducted in mice, rats, and dogs to establish a preclinical safety profile for this drug. Clinical signs following single intraperitoneal doses included hypoactivity, tremors, decreased muscle tone, ataxia, prostration, and labored breathing. Death was observed after intraperitoneal but not oral administration. A consistent drug-related effect noted in all multiple-dose studies with this compound was decreased body weight and food consumption. The only other consistent change noted in multiple-dose studies with felbamate was an increase in liver weight (relative and absolute) in the rat and dog which was accompanied in some cases by increases in serum enzyme levels. No histopathological changes were observed in the liver that could explain these elevated serum enzyme levels. Based on the results of these studies it was concluded that long-term administration of felbamate in human clinical trials was warranted.
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PMID:Acute, subchronic, and chronic toxicity studies with felbamate, 2-phenyl-1,3-propanediol dicarbamate. 984 29

This report focuses on recent studies that investigated the effects of kerosine dermal exposure on neurotoxicity and reproductive/developmental toxicity. Background toxicity information will also be reviewed for kerosine range mid distillates. The kerosine range mid distillates have a carbon range of C9-C16 and have a boiling range of 302-554 degrees F (150-290 degrees C). This category includes kerosine, aviation fuels (e.g., Jet A, JP-5 and JP-8), no. 1 fuel oil and diesel fuel oil. In general, the kerosine range mid distillates demonstrate relatively low acute toxicity by any route of exposure. High inhalation exposures can induce central nervous system depression characterized by ataxia, hypoactivity and prostration. Kerosines are known to cause skin irritation and inflammation under conditions of acute and repeated exposure in animals and humans, but are only slightly irritating to the eye and are not skin sensitizers. In addition, the absorption of kerosine range mid distillates through the skin has been demonstrated to be fairly rapid, but limited to approximately 10-15% of the applied dose after 24 hours. The kerosine range mid distillates are generally inactive in genetic toxicity tests although positive studies have been reported. Positive results, while at times equivocal, have been reported for straight run kerosine and jet fuel A in the mouse lymphoma assay with metabolic activation, and hydrodesulfurized kerosine (mouse) and jet fuel A (rat) in the bone marrow cytogenetic assay. Effects on the nervous and reproductive systems have been reported in humans and experimental animals under conditions where inhalation and dermal exposure to specific kerosine type fuels are sometimes difficult to separate. Recent laboratory studies have addressed this point and examined the effects of dermal exposure. In these studies, rats were exposed to hydrodesulfurized kerosine by skin application to determine the potential of dermal contact to cause reproductive/developmental toxicity (OECD Guideline 421) or neurotoxicity (TSCA Guidelines on subchronic inhalation and neurotoxicity studies). These studies demonstrated that the highest dose level of kerosine does not induce reproductive/developmental or neurotoxicity effects by skin exposure in rodent studies. The dermal NOEL for HDS kerosine in rats was > or = 494 mg/kg for both neurotoxicity, and reproductive/developmental toxicity.
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PMID:Toxicity of middle distillates from dermal exposure. 1018 76

Gadobenate dimeglumine formulation (E7155) was evaluated for its general toxicity potential following a single intravenous and intracisternal administration to rats. Dosage levels tested were 3.3, 4.5, 6.0 and 8.0 mmol/kg at the injection rate of 6 ml/min and 7.50, 8.89, 10.54 and 12.50 mmol/kg at 1 ml/min for the intravenous administration route, and 0.15, 0.21, 0.29 and 0.40 mmol/kg for the intracisternal administration route. Parameters measured during the 14-day observation period were mortality, clinical signs and macroscopic examination. After intravenous administration at the injection rate of 6 ml/min, twitches, respiratory blocking and prostration were observed at 6.0 mmol/kg, and dyspnoea and sedation at 3.3 and 4.5 mmol/kg. Deaths occurred within 1 min after administration at 6.0 mmol/kg and above. LD50 values were 7.97 mmol/kg in males and 6.22 mmol/kg in females. After intravenous administration at the injection rate of 1 ml/min, shallow breathing, twitches and sedation were observed at 7.50 mmol/kg and above and respiratory arrest at 8.89 mmol/kg. Deaths occurred within 1 min after administration at 8.89 mmol/kg and above. LD50 values were 9.0 mmol/kg in males and 9.7 mmol/kg in females. After intracisternal administration, symptoms consisted of sedation, staggering gait, dyspnoea, twitches and ataxia at 0.15 mmol/kg and above, prostration, paralysis of forelimbs, and/or hind limbs and chromodacryorrhea at 0.21 mmol/kg, and convulsions at 0.29 mmol/kg and above. Deaths occurred within 7 days after administration at 0.21 mmol/kg and within 5 min at 0.29 mmol/kg and above. LD50 values were 0.42 mmol/kg in males and 0.25 mmol/kg in females.
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PMID:[General toxicity study of gadobenate dimeglumine formulation (E7155) (1)--single dose intravenous and intracisternal toxicity study in rats]. 1063 76

t-Butyl alcohol is widely used in the manufacture of perfumes and a variety of cosmetics. It is also used as a raw material in the production of isobutylene, which may be used to produce methyl tertiary butyl ether, a common gasoline additive, or to produce butyl elastomers used in the production of automobile tires. The National Cancer Institute nominated t-butyl alcohol to the NTP for study as a result of a review of chemicals found in drinking water. In addition to the high annual production and the potential for occupational exposure, there is also a potential for human exposure to t-butyl alcohol by the inhalation route from its use as an additive in unleaded gasoline. Therefore, toxicity studies of t-butyl alcohol were conducted in male and female F344/N rats and B6C3F1 mice by whole-body inhalation. Animals were evaluated for hematology, clinical chemistry, urinalysis, reproductive toxicity, and histopathology. The genetic toxicity of t-butyl alcohol was assessed by testing the ability of the chemical to induce mutations in various strains of Salmonella typhimurium and L5178Y mouse lymphoma cells or sister chromatid exchanges and chromosomal aberrations in cultured Chinese hamster ovary cells, and by measuring the frequency of micronucleated erythrocytes in rat bone marrow and mouse peripheral blood. In the 18-day inhalation studies, groups of five male and five female rats and mice were exposed to t-butyl alcohol by inhalation at concentrations of 450, 900, 1,750, 3,500, and 7, 000 ppm for 6 hours per day, 5 days per week, for 12 exposure days. All rats and mice exposed to 7,000 ppm were killed moribund following a single 6-hour exposure. One 3,500 ppm male mouse died on day 3. Final mean body weights of 3,500 ppm male and female rats were significantly lower than those of the controls. Final mean body weights and body weight gains of all other exposed groups were similar to those of the controls. In animals exposed to 3.500 ppm, the thymus weights of male and female rats and female mice were less than those of the controls. The liver weights of male and female mice exposed to 3,500 ppm were greater than those of the controls. No grss or microscopic lesion were present in rats or mice. In the 13-week inhalation studies, groups of 10 male and 10 female rats and mice were exposed to t-butyl alcohol at concentrations of 0, 135, 270, 540, 1,080, and 2,100 ppm for 6 hours per day, 5 days per week, for 13 weeks. One 2,100 ppm and five 1,080 ppm male mice died before the end of the studies. The final mean body weight of 2,100 ppm female mice and the mean body weight gains of 1,080 and 2,100 ppm female mice were significantly lower than those of the controls. Clinical findings of toxicity in the 1,080 ppm male mice died during the studies included rough coats and emaciated appearance, hypoactivity, and prostration. Minimal decreases in hematocrit values, hemoglobin concentrations, and erythrocyte counts occurred in the 1,080 and 2,100 ppm male rats at week 13. Hemoglobin concentrations and/or hematocrit values were also minimally decreased in male rats in the lower exposure groups. At week 13, a minimal decrease in urine pH occurred in the 1,080 ppm female and 2,100 ppm male and female rats. Neutrophilia occurred in the 2,100 ppm male mice. Organ weight differences in exposed rats included increased absolute and relative kidney weights of 1,080 ppm males and 2,100 ppm males and females and increased relative liver weights of 1,080 and 2,100 ppm females. There were no treatment-related gross findings in male or female rats or mice; no microscopic lesion occurred in female rats or male or female mice that survived to the end of the study. In male rats, there was an exposure concentration-related increase in the severity of chronic nephropathy. Splenic lymphoid depletion was present in male mice that died during the studies; this lesion was presumed to be secondary to stress. t-butyl alcohol produced no adverse effects on reproductive parameters in male or female rats or mice. The results of all tests of t-butyl alcohol for induction of genetic damage in vitro and in vivo were negative. In vitro, t-butyl alcohol was negative in Salmonella typhimurium and mouse lymphoma cell mutation test, and it did not induce sister chromatid exchanges or chromosomal aberrations in cultured Chinese hamster ovary cells. These in vitro studies were conducted with and without metabolic activation (S9). In vivo, no increase in the frequency of micronucleated erythrocytes was observed in peripheral blood samples from mice administered t-butyl alcohol in drinking water for 13 weeks. Also, induction or micronucleated erythrocytes was noted in bone marrow cells of rats administered t-butyl alcohol by intraperitoneal injection. In summary, inhalation exposure of rats and mice to t-butyl alcohol resulted in deaths following a single 7,000 ppm exposure and clinical findings of alcohol toxicity (hyper- and hypoactivity, ataxia) at concentrations of 900 ppm and greater in rats and 1,750 ppm and greater in mice. In 13-week studies at concentrations up to 2,100 ppm, only one death (that of a 2,100 ppm mouse) was attributed to chemical exposure. The most notable evidence of toxicity at the end of 13 weeks was limited to males and consisted of increased kidney weights, which correlated microscopically to increased severity of chronic nephropathy. Reproductive parameters in male and female rats and mice were unaffected after 13 weeks of exposure, and the results of all tests for genetic toxicity were negative.
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PMID:NTP technical report on toxicity studies of t-butyl alcohol (CAS No. 75-65-0). Administered by inhalation to F344/N rats and B6C3F1 mice. 1180 4

[carisoprodol structure: see text] Carisoprodol is a widely used skeletal muscle relaxant and analgesic and is available as a prescription drug. Comparative studies were conducted to determine the toxicity of carisoprodol administered in corn oil and in 0.5% methylcellulose by gavage. Carisoprodol plasma concentrations of rats and mice were measured at the end of the 13-week studies; single-dose plasma carisoprodol analyses were also performed. Genetic toxicity studies were conducted in Salmonella typhimurium, L5178Y mouse lymphoma cells, cultured Chinese hamster ovary cells, and peripheral blood erythrocytes of mice. Groups of 10 male and 10 female F344/N rats received 0, 100, 200, 400, 800, or 1,600 mg carisoprodol per kilogram body weight in corn oil by gavage or 0, 100, 200, 400, or 800 mg/kg carisoprodol in 0.5% methylcellulose by gavage for 13 weeks. Groups of 10 male and 10 female B6C3F1 mice received 0, 75, 150, 300, 600, or 1,200 mg/kg carisoprodol in corn oil by gavage or 0, 600, 1,200, or 1,600 mg/kg carisoprodol in 0.5% methylcellulose by gavage for 13 weeks. Among rats that received carisoprodol in corn oil, survival was similar to that of the vehicle controls. Survival of rats administered carisoprodol in 0.5% methylcellulose was also similar to that of the vehicle controls after adjustment for deaths (two males and one female in the 800 mg/kg group and two females in the 400 mg/kg group). The final mean body weight gain of males administered 1,600 mg/kg carisoprodol in corn oil was significantly less than that of the vehicle controls; the final mean body weights and body weight gains of female rats in the 800 and 1,600 mg/kg groups were significantly greater. In the carisoprodol in 0.5% methylcellulose study, males in the 200 mg/kg group and females in the 100 and 800 mg/kg groups had significantly greater mean body weights and body weight gains than did the vehicle controls. Clinical findings in rats administered carisoprodol in corn oil or in 0.5% methylcellulose included lethargy, ataxia, diarrhea, and prostration; the incidences were dose-related, and females were more sensitive than males to the effects of carisoprodol. In the carisoprodol in corn oil study, differences in hematology and clinical chemistry parameters occurred with no consistent patterns. The effects of carisoprodol in 0.5% methylcellulose on hematology and clinical chemistry parameters were not studied. In the corn oil study, the kidney and liver weights of male and female rats administered 200 mg/kg carisoprodol or greater were generally significantly greater than those of the vehicle controls. In the 0.5% methylcellulose study, liver weights were significantly greater in male rats administered 400 or 800 mg/kg and in female rats administered 800 mg/kg carisoprodol compared to the vehicle controls; however, a consistent effect on the kidney weights was not observed. Nephropathy was observed in male rats administered 400 mg/kg carisoprodol or greater in corn oil; the livers of four males in the 1,600 mg/kg group had centrilobular hypertrophy of hepatocytes. No lesions were observed histopathologically in female rats administered carisoprodol in corn oil. In the carisoprodol in 0.5% methylcellulose study, the severity of nephropathy in males administered 200 mg/kg or greater was enhanced, and the incidence of nephropathy in female rats in the 800 mg/kg group was slightly greater than that in the vehicle controls. Plasma carisoprodol concentrations at the end of 13 weeks generally increased with increasing dose in rats administered carisoprodol in corn oil or in 0.5% methylcellulose. The plasma carisoprodol concentrations in rats administered a single gavage dose of carisoprodol in corn oil also increased with increasing dose. In the carisoprodol in corn oil mouse study, two females each in the vehicle control and 75 mg/kg groups and one female each in the 150 and 600 mg/kg groups were accidentally killed; all males survived to the end of the study. One male and one female administered 1,600 mg/kg carisoprodol in 0.5% methylcellulose died; seven mice were accidentally killed. The mean body weights and body weight gains of mice administered carisoprodol in corn oil were generally similar to those of the vehicle controls. The final mean body weights and body weight gains of all groups of males and females administered carisoprodol in 0.5% methylcellulose were significantly less. Clinical findings in the carisoprodol in corn oil study included lethargy, ataxia, tremors, and prostration in male and female mice. Ataxia, lethargy, convulsions, and prostration were observed in all dosed groups of males and females administered carisoprodol in 0.5% methylcellulose. In the carisoprodol in corn oil study, liver weights were significantly greater in males administered 300 mg/kg or greater and in females administered 150 mg/kg or greater than in the vehicle controls. In the carisoprodol in corn oil study, no gross or microscopic lesions were considered related to carisoprodol administration. Minimal to mild centrilobular hypertrophy was observed in the liver of all dosed groups of males and in females in the 1,200 and 1,600 mg/kg groups in the carisoprodol in 0.5% methylcellulose study. The testis weights of males administered 1,200 mg/kg carisoprodol in corn oil were significantly less than those of the vehicle controls; the sperm motility of males in this group was also significantly less than that of the vehicle controls. There were no significant differences in vaginal cytology parameters between dosed and vehicle control females. At the end of the carisoprodol in corn oil study, the concentration of carisoprodol was above the limit of detection in the plasma of only one male mouse each in the 300 and 1,200 mg/kg groups and in four females in the 1,200 mg/kg group. In mice administered a single gavage dose of carisoprodol in corn oil, plasma concentrations increased with increasing dose; peak plasma concentrations occurred at 20 to 120 minutes in males and 60 to 120 minutes in females. In the carisoprodol in 0.5% methylcellulose study, plasma carisoprodol concentrations of female, but not male, mice increased with increasing dose; peak plasma carisoprodol concentrations occurred at 30 minutes postdosing in all groups of males and females. Results of proportionality and bioavailability studies indicated that single gavage doses of 200 to 800 mg/kg carisoprodol in 0.5% methylcellulose in rats or 300 to 1,200 mg/kg in mice were dose proportional; absolute bioavailability values increased with increasing dose, ranging from 15% to 32% for rats and from 18% to 38% for mice. For rats, the bioavailability of carisoprodol in 0.5% methylcellulose was approximately fivefold that of carisoprodol in corn oil; the Cmax values of the dose in 0.5% methylcellulose were approximately threefold those of the dose in corn oil. For mice, no significant difference was observed in the bioavailability of carisoprodol between the vehicles; however, the Cmax values of the dose in 0.5% methylcellulose were 1.5 to 1.75 times those of the dose in corn oil. Carisoprodol was not mutagenic in any of four strains of Salmonella typhimurium, with or without S9 metabolic activation. It did induce mutations in L5178Y mouse lymphoma cells in the absence of S9; with S9, no mutagenic activity was noted in this assay. Results of the sister chromatid exchange test with carisoprodol in cultured Chinese hamster ovary cells were considered equivocal with and without S9. Chromosomal aberrations in cultured Chinese hamster ovary cells were clearly increased by carisoprodol treatment, particularly in the presence of S9. No significant increases in the frequency of micronucleated erythrocytes were observed in peripheral blood samples from male and female mice administered carisoprodol by gavage for 13 weeks. In conclusion, carisoprodol induced ataxia and prostration in rats and mice, increases in liver weights in rats and mice, and nephropathy in male rats. The bioavailability of carisoprodol in 5% methylcellulose was greater than in corn oil. The no-observed-adverse-effect (NOAEL) level of carisoprodol administered in corn oil or in 0.5% methylcellulose was determined to be 100 mg/kg, compared to the clinical dose of 20 mg/kg per day for adults and 5 to 7.5 mg/kg per day for children.
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PMID:NTP toxicity studies of carisoprodol (CAS No. 78-44-4) administered by Gavage to F344/N rats and B6C3F1 mice. 1198 79

Hexachloroethane is used in organic synthesis as a retarding agent in fermentation, as a camphor substitute in nitrocellulose, in pyrotechnics and smoke devices, in explosives, and as a solvent. In previous long-term gavage studies with B6C3F1 mice and Osbourne-Mendel rats (78 weeks of exposure followed by 12-34 weeks of observation), hexachloroethane caused increased incidences of hepatocellular carcinomas in mice. However, survival of low and high dose rats was reduced compared with that of vehicle controls, and the effects on rats were inconclusive. Therefore, additional toxicology and carcinogenesis studies were conducted in F344/N rats by administering hexachloroethane (approximately 99% pure) in corn oil by gavage to groups of males and females for 16 days, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and in Chinese hamster ovary (CHO) cells. Urinalysis was performed in conjunction with the 13-week studies. Sixteen-Day Studies: In the 16-day studies (dose range, 187-3,000 mg/kg), all rats that received 1,500 or 3,000 mg/kg and 1/5 males and 2/5 females that received 750 mg/kg died before the end of the studies. Final mean body weights of rats that received 750 mg/kg were 25% lower than that of vehicle controls for males and 37% lower for females. Compound-related clinical signs seen at 750 mg/kg or more included dyspnea, ataxia, prostration, and excessive lacrimation. Other compound-related effects included hyaline droplet formation in the tubular epithelial cells in all dosed males and tubular cell regeneration and granular casts in the tubules at the corticomedullary junction in the kidney in males receiving 187 and 375 mg/kg. Thirteen-Week Studies: In the 13-week studies (dose range, 47-750 mg/kg), 5/10 male rats and 2/10 female rats that received 750 mg/kg died before the end of the studies. The final mean body weight of male rats that received 750 mg/kg was 19% lower than that of vehicle controls. Compound-related clinical signs for both sexes included hyperactivity at doses of 94 mg/kg or higher and convulsions at doses of 375 or 750 mg/kg. The relative weights of liver, heart, and kidney were increased for exposed males and females. Kidney lesions were seen in all dosed male groups, and the severity increased with dose. Papillary necrosis and tubular cell necrosis and degeneration in the kidney and hemorrhagic necrosis in the urinary bladder were observed in the five male rats that received 750 mg/kg and died before the end of the studies; at all lower doses, hyaline droplets, tubular regeneration, and granular casts were present in the kidney. No chemical-related kidney lesions were observed in females. Foci of hepatocellular necrosis were observed in several male and female rats at doses of 188 mg/kg or higher. Dose selection for the 2-year studies was based primarily on the lesions of the kidney in males and of the liver in females. Studies were conducted by administering hexachloroethane in corn oil by gavage at 0, 10, or 20 mg/kg body weight, 5 days per week, to groups of 50 male rats. Groups of 50 female rats were administered 0, 80, or 160 mg/kg on the same schedule. Body Weight and Survival in the Two-Year Studies: Mean body weights of high dose rats were slightly (5%-9%) lower than those of vehicle controls toward the end of the studies. No significant differences in survival were observed between any groups of rats (male: vehicle control, 31/50; 10 mg/kg, 29/50; 20 mg/kg, 26/50; female: vehicle control, 32/50; 80 mg/kg, 27/50; 160 mg/kg, 32/50). Nonneoplastic and Neoplastic Effects in the Two-Year Studies: Incidences of kidney mineralization (vehicle control, 2/50; low dose, 15/50; high dose, 32/50) and hyperplasia of the pelvic transitional epithelium (0/50; 7/50; 7/50) were increased in dosed male rats. Renal tubule hyperplasia was observed at an increased incidence in high dose male rats (2/50; 4/50; 11/50). These lesions have been described as characteristic of the hyaline droplet nephropathy that is associated with an accumulation of liver-generateted with an accumulation of liver-generated a2μ-globulin in the cytoplasm of tubular epithelial cells. The severity of nephropathy was increased in high dose male rats (moderate vs. mild), and the incidences and severity of nephropathy were increased in dosed females (22/50; 42/50; 45/50). The incidences of adenomas (1/50; 2/50; 4/50), carcinomas (0/50; 0/50; 3/50), and adenomas or carcinomas (combined) (1/50; 2/50; 7/50) of the renal tubule were also increased in the high dose male group. One of the carcinomas in the high dose group metastasized to the lung. No compound-related neoplasms were observed in females. The incidence of pheochromocytomas of the adrenal gland in low dose male rats was significantly greater than that in vehicle controls (15/50; 28/50; 21/49), and the incidences for both dosed groups were greater than the mean historical control incidence (28% ± 11%). Genetic Toxicology: Hexachloroethane was not mutagenic in S. typhimurium strains TA98, TA100, TA1535, or TA1537 when tested with and without exogenous metabolic activation. In CHO cells, hexachloroethane did not induce chromosomal aberrations with or with out metabolic activation but did produce sister chromatid exchanges in the presence of exogenous metabolic activation. Audit: The data, documents, and pathology materials from the 2-year studies of hexachloroethane have been audited. The audit findings show that the conduct of the studies is documented adequately and support the data and results given in this Technical Report. Conclusions: Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenic activity of hexachloroethane for male F344/N rats, based on the increased incidences of renal neoplasms. The marginally increased incidences of pheochromocytomas of the adrenal gland may have been related to hexachloroethane administration to male rats. There was no evidence of carcinogenic activity of hexachloroethane for female F344/N rats administered 80 or 160 mg/kg by gavage for 103 weeks. The severity of nephropathy and incidences of linear mineralization of the renal papillae and hyperplasia of the transitional epithelium of the renal pelvis were increased in dosed male rats. The incidences and severity of nephropathy were increased in dosed female rats. Synonyms: carbon hexachloride; ethane hexachloride; hexachlorethane; hexachloroethylene; 1,1,1,2,2,2-hexachloroethane; perchloroethane Trade Names: Avlothane; Distokal; Distopan; Distopin; Egitol; Falkitol; Fasciolin; Mottenhexe; Phenohep
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PMID:Toxicology and Carcinogenesis Studies of Hexachloroethane (CAS No. 67-72-1) in F344/N Rats (Gavage Studies). 1269 80

Butanal oxime is used as a volatile antiskinning agent in paints, inks, and similar products. Butanal oxime was chosen for toxicology testing as a representative of the aldoxime class. Male and female F344/N rats and B6C3F1 mice received butanal oxime (99 percent pure) in drinking water for 15 days or by gavage in 0.5 percent methylcellulose for 14 weeks. Animals were evaluated for clinical pathology, reproductive system effects, and histopathology. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and mouse peripheral blood erythrocytes. In the 15-day studies, groups of five male and five female rats and mice received 0, 312, 625, 1,250, 2,500, or 5,000 ppm butanal oxime in drinking water, resulting in average daily doses of approximately 40, 70, or 100 mg butanal oxime/kg body weight to male and female rats; 45, 90, 130, 200, or 300 mg/kg to male mice; and 45, 85, 100, 130, or 170 mg/kg to female mice. Due to body weight loss and lack of water consumption, all male and female rats receiving 2,500 or 5,000 ppm were removed from the study on day 9; average daily doses were not calculated for these groups. All other rats and mice survived until the end of the studies. Mean body weights of 1,250 ppm male and female rats and 2,500 and 5,000 ppm male and female mice were significantly less than those of the controls. Male mice receiving 5,000 ppm and females receiving 2,500 or 5,000 ppm lost weight during the study. Water consumption by rats and mice receiving 1,250 ppm or greater was less than that by the controls. Thinness in 2,500 and 5,000 ppm rats and mice was the only clinical finding of toxicity. Spleen weights were significantly decreased in 2,500 and 5,000 ppm female mice. No chemical-related lesions were observed grossly; histologic examinations were not performed. In the 14-week studies, groups of 10 male and 10 female rats and mice received butanal oxime by gavage at doses of 0, 25, 50, 100, 200, or 600 mg/kg, 5 days per week for 14 weeks. All 600 mg/kg rats died or were killed moribund during the first week of the study; in the 600 mg/kg mouse groups, seven males and nine females died, were killed moribund, or were killed accidentally before the end of the study. Mean body weights of 100 and 200 mg/kg male rats, 600 mg/kg male mice, and female mice administered 50 mg/kg or greater were less than those of the controls. Clinical findings of toxicity in 600 mg/kg rats included loss of coordination, wobbly gait, shaking, blinking, constant grooming and scratching of the face, head weaving, burying of the face in bedding, lethargy, and prostration; in 600 mg/kg mice, clinical findings included ataxia, loss of balance after rearing, squinting, and burying of the face in the bedding. Hematology results of the 14-week gavage studies indicate that butanal oxime induces a methemoglobinemia and a responsive anemia in rats and mice. Spleen weights of 100 and 200 mg/kg male rats, female rats administered 50 mg/kg or greater, and 200 and 600 mg/kg male mice were increased, as were the liver weights of 200 mg/kg female rats and mice. In animals that died early due to butanal oxime administration, hepatocellular necrosis was the primary pathologic finding. Degeneration of the nasal olfactory epithelium was observed in dosed rats and mice that died early as well as in animals that survived to the end of the studies. Additional chemical-related nasal findings were respiratory epithelial changes in male rats and suppurative exudate in male and female mice. Increased incidences and/or severities of splenic hematopoietic cell proliferation and pigmentation (hemosiderin) as well as bone marrow hyperplasia were also observed in dosed groups, particularly in the 200 and 600 mg/kg groups, and were indicative of erythrocyte damage. Butanal oxime (3 to 10,000 ug/plate) was mutagenic in S. typhimurium strain TA1535 in the presence of 5 percent or 10 percent rat liver S9; an equivocal response was seen in TA100 with 30 percent rat S9, and no mutagenic activity was seen in TA98, with or without rat or hamster liver S9. Butanal oxime induced chromosomal aberrations in cultured Chinese hamster ovary cells, with and without S9. Significant increases in the frequencies of micronucleated normochromatic erythrocytes were observed in vivo in peripheral blood of male and female mice administered 25 to 600 mg/kg butanal oxime for 14 weeks by gavage. Synonyms: Butanaloxime; butylaldoxime; butyraldehyde oxime; n-butyraldehyde oxime; butyraldoxime; n-butyraldoxime Trade names: Exkin 1, Exkin No. 1 Anti-Skinning Agent, Skino #1, Troykyd Anti-Skin BTO
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PMID:NTP technical report on the toxicity studies of Butanal oxime (CAS No. 110-69-0) administered in drinking water and by gavage to F344/N rats and B6C3F1 mice. 1501 36

n-Butyl Alcohol is a primary aliphatic alcohol historically used as a solvent in nail care cosmetic products, but new concentration of use data indicate that it also is being used at low concentrations in eye makeup, personal hygiene, and shaving cosmetic products. n-Butyl Alcohol has been generally recognized as safe for use as a flavoring substance in food and appears on the 1982 Food and Drug Administration (FDA) list of inactive ingredients for approved prescription drug products. n-Butyl Alcohol can be absorbed through the skin, lungs, and gastrointestinal tract. n-Butyl Alcohol may be formed by hydrolysis of butyl acetate in the blood, but is rapidly oxidized. The single oral dose LD(50) of n-Butyl Alcohol for rats was 0.79 to 4.36 g/kg. The dermal LD(50) for rabbits was 4.2 g/kg. Inhalation toxicity studies in humans demonstrate sensory irritation of the upper respiratory tract, but only at levels above 3000 mg/m(3). Animal studies demonstrate intoxication, restlessness, ataxia, prostration, and narcosis. Exposures of rats to levels up to 4000 ppm failed to produce hearing defects. High concentrations of n-Butyl Alcohol vapors can be fatal. Ocular irritation was observed for n-Butyl alcohol at 0.005 ml of a 40% solution. The behavioral no-effect dose for n-Butyl Alcohol injected subcutaneously (s.c.) was 120 mg/kg. Fetotoxicity has been demonstrated, but only at maternally toxic levels (1000 mg/kg). No significant behavioral or neurochemical effects were seen in offspring following either maternal or paternal exposure to 3000 or 6000 ppm. n-Butyl Alcohol was not mutagenic in Ames tests, did not induce sister-chromatid exchange or chromosome breakage in chick embryos or Chinese hamster ovary cells, did not induce micronuclei formation in V79 Chinese hamster cells, did not have any chromosome-damaging effects in a mouse micronucleus test, and did not impair chromosome distribution in the course of mitosis. Clinical testing of n-Butyl Alcohol for nonimmunological contact urticaria was negative in 105 subjects. Repeat-insult patch test (RIPT) studies of nail colors and enamels containing 3% n-Butyl Alcohol in one study produced reactions on challenge, but further study linked significant positive reactions to another solvent. In other RIPT studies, only minimal reactions were reported. A photopatch test demonstrated that a nail enamel containing 3% n-Butyl Alcohol resulted in no reactions. Workers complained of ocular irritation, disagreeable odor, slight headache and vertigo, slight irritation of nose and throat, and dermatitis of the fingers and hands when the air concentration of n-Butyl Alcohol was greater than 50 ppm, as compared to an odor threshold in air of 0.83 ppm. The available safety test data were considered adequate to support the safety of n-Butyl Alcohol in all cosmetic product categories in which it is currently used.
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PMID:Final report of the addendum to the safety assessment of n-butyl alcohol as used in cosmetics. 1883 Aug 64


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