Carcinogenicity and chronic toxicity of butyl methacrylate in rats and mice by a two-year inhalation study.

We conducted a two-year inhalation study of butyl methacrylate using F344/DuCrlCrlj rats and B6D2F/Crl mice. Rats were exposed to 0, 30, 125 and 500 ppm (v/v) and mice were exposed to 0, 8, 30 and 125 ppm (v/v) using whole-body inhalation chambers. Non-neoplastic lesions developed in the nasal cavities of both rats and mice, but neoplastic lesions were not found.

Contribution of toxicological pathology to occupational health: lung carcinogenicity of fibrous and particulate substances in rats.

In this review, we focus on the rat pulmonary carcinogenicity of two solid substances, fibrous multi-walled carbon nanotube (MWCNT) and particulate indium tin oxide (ITO). Inhalation exposure to MWNT-7, a type of MWCNTs, and ITO induced lung carcinogenicity in both male and female rats. Toxicity to the alveolar epithelium is induced by macrophages undergoing frustrated phagocytosis or frustrated degradation of engulfed particles (referred to as frustrated macrophages).

Carcinogenicity and chronic toxicity of acrolein in rats and mice by two-year inhalation study.

The carcinogenicity and chronic toxicity of acrolein was examined by whole body inhalation to groups of 50 F344/DuCrlCrlj rats and 50 B6D2F1/Crlj mice of both sexes for two years. The concentration of acrolein was 0, 0.1, 0.

Comparison of single or multiple intratracheal administration for pulmonary toxic responses of nickel oxide nanoparticles in rats.

Objectives: In this study, we focused on the qualitative and quantitative differences of the lung lesions induced by single or multiple intratracheal administration of nickel oxide nanoparticles (NiO).

Methods: Male rats were randomized into groups receiving intratracheal administrations in a single dose or two to four divided doses of 2 mg/kg/bw. Bronchoalveolar lavage fluid (BALF) analyses were performed at 3 and 28 d post-dose.

[Background data of spontaneous tumors in F344/DuCrlCrlj rats].

Introduction: We investigated the 2-year survival rate and incidence of spontaneous tumors in F344/DuCrlCrlj rats used in carcinogenicity studies of chemical substances. Records for animals used in the control groups of carcinogenicity studies which were conducted during the last 10 years were obtained from the database of the Japan Bioassay Research Center (JBRC). Six hundred ninety-nine males and 550 females were used in 14 and 11 inhalation studies, respectively, and 500 animals of each sex were used in 10 male and 10 female oral studies.

Spontaneous harderian gland adenocarcinoma in a female f344 rat: a case report.

Harderian gland tumors are extremely rare in female F344 rats. An expansive enlarging lesion of the Harderian gland with compression, distortion and invasion of the surrounding muscle was found in a 110-week-old female F344/DuCrj rat, which was diagnosed as a Harderian gland adenocarcinoma. Epithelial growth patterns such as glandular, lobular, papillary and duct forming patterns were exhibited in most areas of the tumor.

Thirteen-week study of toxicity of fiber-like multi-walled carbon nanotubes with whole-body inhalation exposure in rats.

Cancer development due to fiber-like straight type of multi-walled carbon nanotubes (MWCNTs) has raised concerns for human safety because of its shape similar to asbestos. To set concentrations of MWCNT for a rat carcinogenicity study, we conducted a 13-week whole body inhalation study. F344 male and female rats, 6-week-old at the commencement of the study, were exposed by whole-body inhalation to MWCNT at concentrations of 0, 0.

Inhalation carcinogenicity of dichloromethane in rats and mice.

The carcinogenicity of inhaled dichloromethane (DCM) was examined by exposing groups of 50 F344/DuCrj rats and 50 Crj: BDF1 mice of both sexes to 0, 1000, 2000, or 4000 ppm (w/w) DCM-containing aerosol for 2 years. Inhalation of DCM resulted in increased incidences of subcutis fibromas, mammary gland fibroadenoma, and peritoneum mesotheliomas in male rats; mammary gland fibroadenomas in female rats; and bronchiolar-alveolar adenomas and carcinomas in the lung and hepatocellular adenomas and carcinomas in male and female mice. These results clearly indicate that inhaled DCM is carcinogenic in F344/DuCrj (SPF) rats and Crj: BDF1 (SPF) mice.

Lack of micronucleus induction activity of ethyl tertiary-butyl ether in the bone marrow of F344 rats by sub-chronic drinking-water treatment, inhalation exposure, or acute intraperitoneal injection.

Ethyl tertiary-butyl ether (ETBE) is an oxygenated gasoline additive synthesized from ethanol and isobutene that is used to reduce CO2 emissions. To support the Kyoto Protocol, the production of ETBE has undergone a marked increase. Previous reports have indicated that exposure to ETBE or methyl tertiary-butyl ether resulted in liver and kidney tumors in rats and/or mice.

Two-week Toxicity of Multi-walled Carbon Nanotubes by Whole-body Inhalation Exposure in Rats.

To evaluate pulmonary toxicity of multi-walled carbon nanotubes (MWCNTs), F344 rats of both sexes were exposed by inhalation to 0.2, 1 or 5 mg/m(3) MWCNT aerosol for 6 h/day, 5 days/week for 2 weeks using a whole-body exposure system. At the end of the 2-week exposure period, one-half of the rats were necropsied, and at the end of an additional 4-week postexposure period, the remaining rats were necropsied.

Hepatotumorigenicity of ethyl tertiary-butyl ether with 2-year inhalation exposure in F344 rats.

Carcinogenicity of ethyl tertiary-butyl ether (ETBE) was examined with inhalation exposure using F344/DuCrlCrlj rats. Groups of 50 male and 50 female rats, 6 week old at commencement, were exposed to ETBE at 0, 500, 1,500 or 5,000 ppm (v/v) in whole-body inhalation chambers for 6 h/day, 5 days/week for 104 weeks. A significant increase in the incidence of hepatocellular adenomas was indicated in males exposed at 5,000 ppm, but not in females at any concentration.

No carcinogenicity of ethyl tertiary-butyl ether by 2-year oral administration in rats.

The carcinogenicity of ethyl tertiary-butyl ether (ETBE) was examined by oral administration using F344/DuCrlCrlj rats. Groups of 50 male and 50 female rats were given drinking water containing ETBE at doses of 0, 625, 2,500 or 10,000 ppm (w/w) for 104 weeks. No significant increase in the incidence of tumors was detected in any organ of either sex.

2,4-Dichloro-1-nitrobenzene exerts carcinogenicities in both rats and mice by two years feeding.

Carcinogenicity and chronic toxicity of 2,4-dichloro-1-nitrobenzene (2,4-DCNB) were examined by dietary administration to F344/DuCrj rats and Crj:BDF(1) mice of both sexes for 2 years. Dietary administration commenced when the animals were 6 weeks old. The dietary concentration of 2,4-DCNB was 0 (control), 750, 1,500 and 3,000 ppm (w/w) for male and female rats; 0, 750, 1,500 and 3,000 ppm for male mice; and 0, 1,500, 3,000 and 6,000 ppm for female mice.

Carcinogenicity of ortho-phenylenediamine dihydrochloride in rats and mice by two-year drinking water treatment.

The carcinogenicity of ortho-phenylenediamine (o-PD) was examined by administrating o-phenylenediamine dihydrochloride (o-PD2HCl) in dinking water to groups of 50 F344/DuCrj rats and 50 Crj:BDF₁ mice of both sexes for 2 years. The drinking water concentration of o-PD2HCl was 0, 500, 1,000 or 2,000 ppm (wt/wt) for male rats; 0, 250, 500 or 1,000 ppm for female rats; 0, 500, 1,000 or 2,000 ppm for male mice; and 0, 1,000, 2,000 or 4,000 ppm for female mice. Two-year administration of o-PD2HCl produced a dose-dependent increase in the incidences of hepatocellular adenomas and carcinomas in rats of both sexes and in female mice, and hepatocellular adenomas in male mice.

Two- and 13-week inhalation toxicities of indium-tin oxide and indium oxide in rats.

Objectives: Two- and 13-week inhalation toxicities of indium-tin oxide (ITO) and indium oxide (IO) were characterized for risk assessments of workers exposed to ITO.

Methods: F344 rats of both sexes were exposed by inhalation to ITO or IO aerosol for 6 h/day, 5 day/wk for 2 wk at 0, 0.1, 1, 10 or 100 mg/m(3) or 13 wk at 0, 0.

Translocation of intratracheally instilled multiwall carbon nanotubes to lung-associated lymph nodes in rats.

In order to assess the extrapulmonary effects of multiwall carbon nanotubes (MWCNT), deposition of MWCNT and histopathologic changes in lung-associated lymph nodes (LALN) were examined in MWCNT-administered rats. At the age of 13 wk, male F344 rats were intratracheally instilled with MWCNT at a dose of 0 (vehicle), 40 or 160 μg/rat. The rats were sacrificed on Day 1, 7, 28 or 91 after instillation and light microscopic examinations were performed on LALN tissues.

Inhalation carcinogenicity and toxicity of 1,2-dichloropropane in rats.

The toxicity and carcinogenicity of 1,2-dichloropropane (DCP) were examined by inhalation exposure of male and female F344 rats to DCP for either 13 wk or 2 years. In the 13-wk study, the DCP concentrations used were 125, 250, 500, 1000, or 2000 ppm (v/v), and in the 2-year study the DCP concentrations were 80, 200, or 500 ppm (v/v). Thirteen-week exposure to DCP induced hyperplasia in the respiratory epithelium and atrophy of the olfactory epithelium at 125 ppm and above.

Characteristics of multiwall carbon nanotubes for an intratracheal instillation study with rats.

Much concern has been raised over the health consequences of workers exposed to carbon nanotubes. In order to characterize multi-wall carbon nanotubes (MWCNT) suspended in a phosphate-buffered saline containing 0.1% Tween 80 for an intratracheal instillation study.

Pulmonary toxicity of intratracheally instilled multiwall carbon nanotubes in male Fischer 344 rats.

In order to assess pulmonary toxicity of multiwall carbon nanotubes (MWCNT), male F344 rats were intratracheally instilled with MWCNT suspension at a dose of 40 or 160 μg/head or α-quartz particles as a positive control at a dose of 160 μg/head and sacrificed for lung histopathology and bronchoalveolar lavage (BAL) fluid analyses on Day 1, 7, 28 or 91 after instillation. Well-dispersed MWCNT brought about dose- or time-dependent changes in lung weight, total proteins, albumin, lactate dehydrogenase and alkaline phosphatase in the BAL fluid, and pulmonary lesions including inflammation, Type II cell hyperplasia, microgranulomas and fibrosis. Phagocytosed and free forms of MWCNT were found in both bronchiolar and alveolar spaces.

Enhanced proliferative response of hepatocytes to combined inhalation and oral exposures to N,N-dimethylformamide in male rats.

Male Wistar rats were exposed by inhalation to N,N-dimethylformamide (DMF) at 0 (control), 200 or 400 ppm (v/v) for 6 hr/day, 5 days/week and 4 weeks, and each inhalation group received DMF-formulated drinking water at 0, 800, 1,600 or 3,200 ppm (w/w) for 24 hr/day, 7 days/week and 4 weeks. Both the combined inhalation and oral exposures and the single-route exposure through inhalation or ingestion induced centrilobular hypertrophy and single-cell necrosis of hepatocytes, increased plasma levels of alanine aminotransferase (ALT), increased percentage of proliferating cell nuclear antigen (PCNA)-positive hepatocytes without glutathione-S-transferase placental form (GST-P)-positive liver foci, and increased relative liver weight. Those hepatic parameters of the DMF-induced effects were classified into hypertrophic, necrotic and proliferative responses according to the pathological characteristics of affected liver.

Thirteen-week inhalation toxicity of 1,4-dioxane in rats.

Thirteen-week inhalation toxicity of 1,4-dioxane was examined by repeated inhalation exposure of male and female F344 rats to 0 (control), 100, 200, 400, 800, 1600, 3200, or 6400 ppm (v/v) 1,4-dioxane vapor for 6 h/day and 5 days/wk. All the 6400-ppm-exposed males and females died during the first week. Terminal body weight decreased, and relative weights of liver, kidney, and lung increased.

Thirteen-week oral toxicity of 1,4-dioxane in rats and mice.

Subchronic oral toxicity of 1,4-dioxane was examined by administering 1,4-dioxane in drinking water at 6 different concentrations of 0 (control), 640, 1,600, 4,000, 10,000 or 25,000 ppm (wt/wt) to F344 rats and BDF(1)mice of both sexes for 13 weeks. Food and water consumption and terminal body weight were decreased dose-dependently in rats and mice. A dose-dependent increase in the relative weights of kidney and lung was noted in rats and mice, while the relative liver weight was increased only in rats.

Occurrence of two different types of glutathione S-transferase placental form-positive hepatocytes after a single administration of 2,3,7,8-tetrabromodibenzo-p-dioxin in rats.

Occurrence of glutathione S-transferase placental form (GST-P)-positive hepatocytes was examined, using 15 Wistar rats of both sexes each orally administered 2,3,7,8-tetrabromo-dibenzo-p-dioxin (TBDD) by gavage at a single dose of 0, 10, 30, 100 or 300 microg/kg body weight. Liver tissues were stained with anti-GST-P antibody. Two different types of GST-P-positive hepatocytes were found in the TBDD-dosed rat.