National Toxicology Program technical report series最新文献

Triclosan is a broad-spectrum antimicrobial agent to which humans are widely exposed. Very limited data are available regarding the dermal toxicity and the carcinogenic potential of triclosan. In this study, groups of 48 male and 48 female B6C3F1/N mice were untreated or were dermally administered 0 (vehicle), 1.25, 2.7, 5.8, or 12.5 mg triclosan/kg body weight/day (mg/kg/day) in 95% ethanol, 7 days per week for 2 years. Vehicle control animals received 95% ethanol only; untreated, naive control mice were not dosed. There were no significant differences in survival among the groups. The highest dose of triclosan decreased the body weights of mice in both sexes, but the decrease was ≤8%. (Abstract Abridged).

Black cohosh (Actaea racemose L.) is widely used as a botanical dietary supplement to alleviate female gynecological symptoms, such as premenstrual syndrome and changes associated with menopause, and to stimulate labor. Despite its popularity, limited data are available on the long-term safety of black cohosh products. To address this knowledge gap, 2-year National Toxicology Program (NTP) carcinogenicity studies were conducted in Sprague Dawley (Hsd:Sprague Dawley SD) rats and B6C3F1/N mice. To emulate a potential human exposure scenario in which a woman might use black cohosh throughout pregnancy and lactation, perinatal exposure was included for the rat study. (Abstract Abridged).

Tris(chloropropyl) phosphate (TCPP) is used as a flame retardant in textiles, furniture foam, and other related products. In addition, it is manufactured for use in construction materials, electronic products, paints, coatings, and adhesives. Several flame retardants, including structurally similar organohalogen compounds, have been removed from products in commerce due to toxicity concerns, and TCPP has been proposed as a replacement flame retardant for use in these products. An anticipated increase in use of TCPP has generated concerns for increased human exposure through oral, dermal, and inhalation routes; however, publicly available toxicity data are scarce. The U.S. Consumer Product Safety Commission therefore requested that the National Toxicology Program (NTP) form a research program on TCPP to conduct subchronic and chronic exposure studies in rats and mice for hazard identification and characterization information. Because TCPP is commercially available as an isomeric mixture, the NTP studies tested a commercial TCPP product containing four isomers commonly found in other commercial mixtures of TCPP: tris(1-chloro-2-propyl) phosphate (TCIPP; CASRN 13674-84-5), bis(2-chloro-1-methylethyl) 2-chloropropyl phosphate (CASRN 76025-08-6), bis(2-chloropropyl) 2-chloroisopropyl phosphate (CASRN 76649-15-5), and tris(2-chloropropyl) phosphate (CASRN 6145-73-9). Following procurement of TCPP, the percent purity of the four isomers was determined prior to conducting hazard characterization studies. (Abstract Abridged).

Di(2-ethylhexyl) phthalate (DEHP) is a member of the phthalate ester chemical class that occurs commonly in the environment and to which humans are widely exposed. Lifetime exposure to DEHP is likely to occur, including during the in utero and early postnatal windows of development. To date, no carcinogenicity assessments of DEHP have used a lifetime exposure paradigm that includes the perinatal period (gestation and lactation). The National Toxicology Program (NTP) tested the hypothesis that exposure during the perinatal period would alter the DEHP carcinogenic response quantitatively (more neoplasms) or qualitatively (different neoplasm types). Two chronic carcinogenicity assessments of DEHP were conducted in which Sprague Dawley (Hsd:Sprague Dawley SD) rats were exposed to dosed feed containing 0, 300, 1,000, 3,000, or 10,000 ppm DEHP for 2 years using different exposure paradigms. In Study 1, groups of 45 F0 time-mated females were provided dosed feed beginning on gestation day (GD) 6 through lactation. On postnatal day (PND) 21, groups of 50 F1 rats per sex continued on the study and were provided dosed feed containing the same DEHP concentration as their respective dam for 2 years. In Study 2, groups of 50 rats per sex, aged 6 to 7 weeks at study start, were provided dosed feed containing DEHP for 2 years. (Abstract Abridged).

Sodium tungstate dihydrate (ST) is present naturally in the environment and can enter waterways through the weathering of rocks and soils. ST also is a high-production volume compound that is used in a variety of commercial applications including fire- and waterproofing fabrics, in the preparation of complex compounds (e.g., phosphotungstate and silicotungstate), as a reagent for biological products, and as a precipitant for alkaloids. Tungsten was nominated to the National Toxicology Program (NTP) by the Centers for Disease Control and Prevention to evaluate its potential to cause chronic toxicity and carcinogenicity because of concern about potential human exposure via contaminated drinking water (e.g., in the form of salts like tungstate) and inadequate data to assess human health implications of elevated exposures. ST was selected for study because it is the most prevalent water-soluble form of tungsten. In these studies, Sprague Dawley (Hsd:Sprague Dawley SD) rat dams were exposed to ST in drinking water from gestation day (GD) 6 through lactation day (LD) 20. Their pups were exposed to the same exposure concentrations in drinking water from postnatal day (PND) 12 through 3 months or 2 years. Adult male and female B6C3F1/N mice were exposed to ST in drinking water for 3 months or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, rat and mouse peripheral blood erythrocytes, and cells from liver, kidney, and ileum; peripheral blood leukocytes from rats and mice also were assessed for DNA damage. (Abstract Abridged).

Di-n-butyl phthalate (DBP) is a phthalate used in the manufacture of consumer products such as plastics and personal care products. Widespread exposure in the population occurs throughout life, including during pregnancy and lactation. Because limited data are available in both animals and humans to evaluate DBP as a human carcinogen, the National Toxicology Program conducted 2-year studies of DBP in rats and mice. Time-mated female Sprague Dawley (Hsd:Sprague Dawley SD) rats were exposed to 0, 300, 1,000, 3,000, or 10,000 ppm DBP in feed during gestation and lactation. Postweaning, F1 offspring consumed diets with the same exposure concentrations as the dam for 2 years (n = 50/sex/exposure group). Male and female adult B6C3F1/N mice were exposed to 0, 1,000, 3,000, or 10,000 ppm DBP in feed for 2 years (n = 50/sex/exposure group). Estimated average chronic chemical consumption was 16-17, 54-57, 152-169, and 510-600 mg DBP/kg body weight/day (mg/kg/day) in rats in the 300, 1,000, 3,000, and 10,000 ppm groups, respectively, and 105-112, 329-347, and 1,306-1,393 mg/kg/day in mice in the 1,000, 3,000, and 10,000 ppm groups, respectively. (Abstract Abridged).

Perfluorooctanoic acid (PFOA) is a perfluorinated alkyl substance (PFAS) with widespread exposure in the environment and human population. Lifetime exposure to this chemical is likely, which includes in utero and postnatal development. Previously conducted chronic carcinogenicity studies of PFOA began exposure after these critical periods of development, so it is unknown whether the carcinogenic response is altered if exposure during gestation and lactation is included. The current PFOA chronic studies were designed to assess the contribution of combined gestational and lactational exposure (herein referred to as perinatal exposure) to the chronic toxicity and carcinogenicity of PFOA. The hypothesis tested was that including exposure during gestation and lactation (perinatal exposure) with postweaning exposure would change the PFOA carcinogenic response quantitatively (more neoplasms) or qualitatively (different neoplasm types) compared to postweaning exposure alone. (Abstract Abridged).

2-Hydroxy-4-methoxybenzophenone (2H4MBP) is approved by the U.S. Food and Drug Administration for use in sunscreens and other personal products in concentrations of up to 6% either alone or in combination formulations and as an indirect food additive in acrylic and modified acrylic plastics that come into contact with food. 2H4MBP was nominated to the National Toxicology Program by the National Cancer Institute due to widespread exposure via sunscreen use and lack of carcinogenicity data. 2H4MBP was also nominated by a private individual to ascertain genotoxic potential. Male and female Sprague Dawley (Hsd:Sprague Dawley SD) rats (after weaning) and B6C3F1/N mice were exposed to 2H4MBP (greater than 99% pure) in feed for 2 years. Perinatal studies and 14-week interim evaluations were also conducted in rats. Genetic toxicology studies were conducted in Salmonella typhimurium and Escherichia coli. (Abstract Abridged).

Zinc is a naturally occurring element and is ubiquitous in the environment. Zinc itself is stable in dry air, but exposure to moist air results in the formation of zinc oxide or basic carbonate. Due to the reactivity of zinc metal, it is not found as a free element in nature but as a variety of different compounds including zinc chloride, zinc oxide, and zinc sulfate. Zinc and zinc compounds are used across a wide range of industries that include rubber production, animal feed supplementation, as a fertilizer additive, in cosmetics and drugs, as a paint pigment, in dental cements, as a wood preservative, in batteries, in galvanizing and metal work, in textile production, in television screens and watches, and in smoke bombs. Of the zinc compounds, zinc oxide is the most widely used. Zinc was nominated by the Agency for Toxic Substances and Disease Registry (ATSDR) for carcinogenicity and genotoxicity testing based on the increasing size of the population exposed to zinc through dietary supplements and the lack of studies examining the carcinogenicity of zinc. There was an additional nomination to investigate the tumorigenicity of zinc deficiency by private individuals as a result of data showing that deficiency of some vitamins and minerals in humans can cause DNA damage. Zinc carbonate basic was selected as the source of dietary zinc due to its use as the source of supplemental zinc in rodent diets. Male and female Hsd:Sprague Dawley SD rats were exposed to dietary zinc in feed for 2 years. Genetic toxicology studies were conducted in rat peripheral blood erythrocytes, peripheral blood leukocytes, and colon epithelial cells. (Abstract Abridged).

The predominant source of human exposure to radio frequency radiation (RFR) occurs through usage of cellular phone handsets. The Food and Drug Administration nominated cell phone RFR emission for toxicology and carcinogenicity testing in 1999. At that time, animal experiments were deemed crucial because meaningful human exposure health data from epidemiological studies were not available. Male and female Sprague Dawley (Hsd:Sprague Dawley SD) rats were exposed to time-averaged whole-body specific absorption rates of Global System for Mobile Communications (GSM)- or Code Division Multiple Access (CDMA)-modulated cell phone RFR at 900 MHz in utero, during lactation, and after weaning for 28 days or 2 years. Genetic toxicology studies were conducted in rat peripheral blood erythrocytes and leukocytes, brain cells, and liver cells. (Abstract Abridged).