Toxicity report series最新文献

Virginia cedarwood oil (hereafter referred to as cedarwood oil) is extracted from Juniperus virginiana trees by steam distillation and contains cedrol, cedrene, cedrenol, cedral, cuperene, thujopsene, and widdrol as primary components. Cedarwood oil is used as a fragrance in cosmetic products, as a pesticide, and as a source material for production of other fragrance materials with cedarwood odors. Cedarwood oil was nominated for toxicity testing by the National Cancer Institute based on widespread and potentially increasing human exposure to the substance, and a lack of toxicology data. The dermal route of administration was selected for these studies because it is the most common route of exposure in humans due to its frequent use as a pesticide and as a fragrance in household products and cosmetics. Male and female F344/N rats and B6C3F1/N mice were administered cedarwood oil dermally for 3 months. Genetic toxicology studies were conducted in Salmonella typhimurium and mouse peripheral blood erythrocytes. (Abstract Abridged).

p-Toluenesulfonamide is formed from chloramine-T, an antimicrobial agent used by the aquaculture industry to treat fish intended for human consumption. Chloramine-T is also widely used as a disinfectant in the medical, dental, veterinary, food processing, and agricultural industries. Because of its low degree of cytotoxicity, chloramine-T has been used in direct contact with tissues, including treatment for burns, in whirlpools for wounds, and as an oral mouthwash. In the agricultural industry, it is used as a broad-spectrum biocide for foot-and-mouth disease, swine vesicular disease, and poultry diseases. Chloramine-T was nominated by a private individual for toxicology studies based on its current status as an Investigational New Animal Drug for controlling proliferative gill disease and bacterial gill disease in aquaculture and the need for additional toxicology studies to support its safe use. p-Toluenesulfonamide was studied for toxicity by the NTP because it has been shown to be the major product formed from chloramine-T. For the 2-week studies, male and female F344/N rats and B6C3F1/N mice were exposed to p-toluenesulfonamide (greater than 99% pure) in feed. For the 3-month studies, male and female F344/NTac rats and B6C3F1/N mice were exposed to p-toluenesulfonamide (greater than 99% pure) in feed. Genetic toxicology studies were conducted in Salmonella typhimurium, rat peripheral blood erythrocytes, and mouse peripheral blood erythrocytes. (Abstract Abridged).

Octahydro-tetramethyl-naphthalenyl-ethanone (OTNE) is a fragrance ingredient that is formed as a mixture of isomers with a basic unsaturated alkyl cyclic ketone structure. The main isomer is 1-(1,2,3,4,5,6,7,8-octahydro-2,3,8,8-tetramethyl-2-naphthalenyl)ethanone (β-isomer). Two other predominant isomers within the mixture are 1-(1,2,3,4,6,7,8,8a-octahydro-2,3,8,8-tetramethyl-2-naphthalenyl)ethanone (α-isomer) and 1-(1,2,3,5,6,7,8,8a-octahydro-2,3,8,8-tetramethyl-2-naphthalenyl)ethanone (γ-isomer). OTNE is used as a perfume ingredient in soap, shampoo, cologne, liquid detergent compounds, and malodor-reducing compounds. Male and female F344/NTac rats and B6C3F1/N mice were administered OTNE (greater than 92.3% pure with respect to the 3 prominent isomers) dermally for 3 months. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, and rat and mouse peripheral blood erythrocytes. (Abstract Abridged).

Sodium thioglycolate is a white powder with a melting point greater than 300 degrees Celsius. It appears as hygroscopic crystals with an unpleasant odor characteristic of the sulfhydryl group (mercaptans). Thioglycolic acid can be prepared by the action of sodium sulfhydrate on sodium chloroacetate and by electrolysis of dithioglycolic acid from sodium sulfide and sodium chloroacetate. It is also formed by heating chloroacetic acid with potassium hydrogen sulfide. Thioglycolic acid and its salts and glyceryl esters are not known to occur naturally. Sodium thioglycolate is used in the cosmetic industry as an antioxidant, depilating agent, hair waving/straightening agent, and reducing agent. Its primary cosmetic use is in depilatories. Sodium thioglycolate is also used as an analytical reagent and in bacteriology for the preparation of thioglycolate media. Sodium thioglycolate was nominated by the National Cancer Institute for toxicology studies due to its high production volume and widespread occupational and consumer exposure to thioglycolic acid and its salts and esters, including significant female exposure in personal care products. Male and female F344/N rats and B6C3F1/N mice were administered sodium thioglycolate (approximately 99% pure) in a vehicle of 95% ethanol:deionized water (1:1) by application to shaved dorsal skin for 16 (rats) or 17 (mice) days or for 3 months. Genetic toxicology studies were conducted in Salmonella typhimurium and mouse peripheral blood erythrocytes. (Abstract Abridged).

α-Pinene is the main component in turpentine and is used as a fragrance and flavoring ingredient. Due to widespread exposure potential and a lack of available toxicity data, male and female F344/N rats and B6C3F1/N mice were exposed to α-pinene (96% pure) by inhalation for 2 weeks or 3 months. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, and mouse peripheral blood erythrocytes. (Abstract Abridged).

5-Amino-o-cresol is used as an oxidative dye coupler (secondary intermediate) or oxidative (permanent) in hair dye formulations. It was nominated for study by the National Cancer Institute because it is a widely used genotoxic hair dye component for which no cancer studies have been reported. Male and female F344/NTac rats and B6C3F1/N mice were administered 5-amino-o-cresol (greater than 99% pure) dermally for 3 months. Genetic toxicology studies were conducted in Salmonella typhimurium, peripheral blood erythrocytes of male and female mice, and bone marrow of male mice. (Abstract Abridged).

Estragole is a natural organic compound that is used as an additive, flavoring agent, or fragrance in a variety of food, cleaning, and cosmetic products; as an herbal medicine; as an antimicrobial agent against acid-tolerant food microflora; and to produce synthetic anise oil. Estragole was nominated for toxicity testing by the National Institute of Environmental Health Sciences to characterize its toxicity when administered by gavage to F344/N rats and B6C3F1 mice and to determine how similar its effects might be to those of the structurally related compound, methyleugenol. Male and female F344/N rats and B6C3F1 mice were given estragole (greater than 99% pure) in corn oil by gavage for 3 months. Genetic toxicology studies were conducted in Salmonella typhimurium and mouse peripheral blood erythrocytes. Core and special study (rats only) groups of 10 male and 10 female rats and mice were administered 37.5, 75, 150, 300, or 600 mg estragole/kg body weight in corn oil by gavage, 5 days per week. The core study groups were given estragole for 3 months and the special study groups for 30 days. All core study rats survived the 3-month exposure period. Mean body weights of the 300 and 600 mg/kg groups were 73% to 92%, respectively, of those of the vehicle control groups. A staining pattern on the ventral surface anterior to the genitalia beginning at week 9 in the 300 and 600 mg/kg groups was attributed to residue of estragole or metabolites in the urine. Alterations in the erythron related to estragole administration occurred in male and female rats; male rats demonstrated a stronger response. The changes in the erythron were characterized as a microcytic, normochromic, nonresponsive anemia. There were decreases in serum iron concentration in the 300 mg/kg females and 600 mg/kg males and females. The average percent saturation of total iron binding capacity was decreased in the 600 mg/kg males and females. Dose-related increases in platelet counts occurred in most of the dosed groups of rats; the effect appeared to be stronger in males. The increase could be consistent with a reactive thrombocytosis. Increases in the serum alanine aminotransferase and sorbitol dehydrogenase activities suggested a hepatocellular effect (increased leakage) and were consistent with the morphological liver changes observed. There were dose-related increases in serum bile salt concentration in most treated male rats at all time points; females were less affected. Absolute and relative liver weights were significantly increased in 300 and 600 mg/kg males and in 75 mg/kg or greater females. Relative kidney weights were significantly increased in all dosed groups of male rats and in female rats given 75 mg/kg or greater. Absolute and relative testis weights of 300 and 600 mg/kg males were significantly decreased. Two 600 mg/kg male rats had multiple cholangiocarcinomas in the liver and a third had an hepatocellular adenoma. All 600 mg/kg males exhibited cholangiofibros

2,4-Decadienal is used as a synthetic flavoring and fragrance material and has been evaluated as a corrosion inhibitor for steel in oil field operations. 2,4-Decadienal was nominated by the National Cancer Institute for toxicity testing because the dienaldehydes occur naturally in a variety of foods and food components, are used as food additive/flavoring agents, and the potential for human exposure is high. In the toxicity studies, male and female F344/N rats and B6C3F1 mice received 2,4-decadienal (at least 93% pure) in corn oil by gavage for 2 weeks or 3 months. Genetic toxicology studies were conducted in Salmonella typhimurium, rat and mouse bone marrow cells, and mouse peripheral blood erythrocytes. In the 2-week studies, groups of five male and five female rats and mice received 2,4-decadienal in corn oil by gavage at doses of 0, 45, 133, 400, 1,200, or 3,600 mg 2,4-decadienal/kg body weight 5 days per week for 16 days. All animals in the 3,600 mg/kg groups were found dead or sacrificed moribund by day 3 (rats) or day 9 (mice). One 133 mg/kg female rat was found dead on day 8, and one male and one female mouse in the 1,200 mg/kg groups were found dead on days 12 and 16, respectively. At 1,200 mg/kg, treatment-related ulceration of the forestomach was observed in male and female rats and mice. Focal necrosis of the forestomach occurred in a 1,200 mg/kg female mouse. Mean body weights of all 1,200 mg/kg groups were less than those of the vehicle controls, and 1,200 mg/kg female mice lost weight during the study. Diarrhea, lethargy, abnormal breathing (rats), and thinness (mice) occurred in the 1,200 and 3,600 mg/kg groups. Gross lesions seen at necropsy included ulcerations of the forestomach in 1,200 mg/kg rats and 1,200 and 3,600 mg/kg mice. Adhesions involving the stomach and other abdominal organs were also seen in 1,200 and 3,600 mg/kg mice. In the 3-month studies, groups of 10 male and 10 female rats and mice received 2,4-decadienal in corn oil by gavage at doses of 0, 50, 100, 200, 400, or 800 mg 2,4-decadienal/kg 5 days per week for 14 weeks. No chemical-related deaths occurred. Mean body weights of 400 mg/kg male rats and 800 mg/kg male and female rats and male mice were significantly less than those of the vehicle controls. Dosed male and female rats were lethargic after week 7; the severity of the lethargy was dose related. There were changes in the leukon of dosed rats compared to vehicle control rats characterized by decreased leukocyte, lymphocyte, and eosinophil counts and increased neutrophil counts. Spleen weights of 800 mg/kg female rats and thymus weights of 400 and 800 mg/kg female rats were significantly less than those of the vehicle controls. Thymus, spleen, testis, cauda epididymis, and epididymis weights of 800 mg/kg male rats were less than those of the vehicle controls. The incidences of epithelial hyperplasia of the forestomach were significantly greater in 400 and 800 mg/kg male and female rats, 200, 400, a

Genistein is a naturally occurring isoflavone that interacts with estrogen receptors and multiple other molecular targets. Human exposure to genistein is predominantly through consumption of soy products, including soy-based infant formula and dietary supplements. A series of short-term studies with genistein was conducted with two goals: 1) to obtain data necessary to establish dose levels for subsequent multigeneration reproductive and chronic toxicity studies and 2) to evaluate the effects of genistein on endpoints outside the reproductive tract. The data generated from these studies have been reported previously in the peer-reviewed literature or in technical reports (Appendix C). In addition, selected data from these studies were analyzed and discussed in the National Toxicology Program's Report of the Endocrine Disruptors Low-Dose Peer Review (NTP, 2001). The present report focuses on the reproductive and general toxicology endpoints evaluated. Data obtained in separate evaluations of behavioral, neuroanatomical, neurochemical, and immunological endpoints, as well as the assessment of serum genistein levels, are also discussed to put in better perspective the selection of doses for the multigenerational and chronic studies. Genistein was administered in an irradiated soy- and alfalfa-free diet (Purina 5K96) at exposure concentrations of 0, 5, 25, 100, 250, 625, or 1,250 ppm to 10 vaginal plug-positive, female Sprague-Dawley rats starting on gestation day 7 and continuing throughout pregnancy. These dietary exposure concentrations resulted in ingested doses of approximately 0.3, 1.7, 6.4, 16, 38, and 72 mg genistein/kg body weight to dams in the 5, 25, 100, 250, 625, and 1,250 ppm groups, respectively. Dietary exposure of the dams continued through lactation, during which time ingested doses were approximately 0.6, 3.5, 14, 37, 84, and 167 mg/kg per day. Pups from five litters, culled to eight per litter with an equal sex distribution on postnatal day (PND) 2, were maintained on the same dosed feed as their mothers after weaning until sacrifice at PND 50. Ingested doses were approximately 0.6, 3, 11, 29, 69, and 166 mg/kg per day for male pups and 0.6, 3, 12, 31, 73, and 166 mg/kg per day for female pups. Body weight and feed consumption of the treated dams prior to parturition showed decreasing trends with increasing dose, and both parameters were significantly less than those of the controls in the 1,250 ppm group. A significant exposure concentration-related effect on litter birth weight was observed, but no exposed group differed significantly from the control group in pairwise comparisons. Pups in the 1,250 ppm group had significantly decreased body weights relative to controls at the time of sacrifice (males, 9% decrease; females, 12% decrease). The most pronounced organ weight effects in the pups were decreased ventral prostate weight (absolute weight, 28% decrease; relative weight, 20% decrease) in males at 1,250 ppm and a tren