摘要:

Carcinogenesis studies of 4,4'‐methylenedianiline dihydrochloride (98.6% pure) were conducted by administering this chemical in the drinking water of F344/N rats and B6C3F1, mice. Croups of 50 rats and 50 mice of each sex received drinking water containing 150 or 300 ppm 4,4'‐methylenedianiline dihydrochloride (dosage expressed as the free base) for 103 wk. Croups of 50 rats and 50 mice of each sex, given drinking water adjusted with 0.1 N HCI to the pH (3.7) of the 300‐ppm formulation, served as controls. Survival was comparable among groups except for male mice receiving the 300‐ppm dose of 4,4'‐methylenedianiline dihydrochloride; survival in that group was lower than that in controls. Mean body weight was reduced in 300‐ppm‐dose female rats and 300‐ppm‐dose male and female mice compared to controls. Water consumption was reduced in a dose‐related manner in both sexes of rats. No compound‐related clinical effects were observed. Under the conditions of these studies, there was clear evidence of carcinogenicity for F344IN rats and for B6C3F1, mice in that 4,4'‐methylenedianiline dihydrochloride caused increased incidences of (1) follicular‐cell carcinomas of the thyroid gland (controls, 0149; low dose, 0/47; high dose, 7/48, 15%; p ≤ 0.072; and neoplastic nodules of the liver (controls, 1/50, 2%; low dose, 12/50, 24%; high dose, 25/50, 50%; p ≤ 0.007; in male rats, (2) follicular‐cell adenomas (controls, 0/47; low dose, 2/47, 4%; high dose, 17/48, 35%; p ≤ 0.001) and C‐cell adenomas (controls, 0/47; low dose, 3/47, 6%; high dose, 6/48, 13% p ≤ 0.029) of the thyroid gland in female rats, (3) follicular‐cell adenomas of the thyroid gland (controls, 0/47; low dose, 3/49, 6%; high dose, 16/49, 33%; p ≤ 0.001), carcinomas of the liver (controls, 10/49, 20%; low dose, 33/50, 66%; high dose, 29/50, 58%; p ≤ 0.001), and pheochromocytomas of the adrenal gland in male mice (controls, 2/48, 4%; low dose, 12/49, 24%; high dose, 14/49, 29%; p ≤ 0.001), and (4) follicular‐cell adenomas of the thyroid gland (controls, 0/50; low dose, 1/47, 2%; high dose, 13/50, 26%; p ≤ 0.001), carcinomas (controls, 1/50, 2%; low dose, 6/50, 12%; high dose, 11/50, 22%; p ≤ 0.002) and adenomas (controls, 3/50, 6%; low dose, 9/50, 18%; high dose, 12/50, 24%; p ≤ 0.011) of the liver, malignant lymphomas (controls, 13/50, 26%; low dose, 28/50, 56%; high dose, 29/50, 58%; p ≤ 0.001), and alveolar/bronchiolar adenoma (controls, 1/50, 2%; low dose, 2150, 4%; high dose, 6/49, 12%; p ≤ 0.05) in female mice.

ISSN:0098-4108    

DOI:10.1080/15287398609530874

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

The nitropolycyclic aromatic hydrocarbon 1‐nitropyrene (1‐NP) is an environmental pollutant, a potent bacterial and mammalian mutagen, and a carcinogen. The metabolism of 1‐NP by the human intestinal microbiota was studied using a semicon‐tinuous culture system that simulates the colonic lumen. [3H]‐1‐Nitropyrene was metabolized by the intestinal microbiota to 1‐aminopyrene (1‐AP) and N‐formyl‐1‐amin‐opyrene (FAP) as determined by high‐performance liquid chromatography (HPLC) and mass spectrometry. Twenty‐four hours after the addition of [3H]‐1‐NP, the formy‐lated compound and 1‐AP accounted for 20 and 80% of the total metabolism, respectively. This percentage increased to 66% for FAP after 24 h following 10 d of chronic exposure to unlabeled 1‐NP, suggesting metabolic adaptation to 1‐NP by the microbiota. Both 1‐AP and FAP have been shown to be nonmutagenic towards Salmonella typhimurium TA98, which indicates that the intestinal microflora may potentially detoxify 1‐NP.

ISSN:0098-4108    

DOI:10.1080/15287398609530875

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

A benzidine‐derived azo dye, C.I. direct black 38 (DB38), and a p‐phenylenediamine‐derived dye, C.I. direct black 19 (DB19), labeled with carbon‐14 in their aromatic amine moieties, were applied to the shaved dorsal skin of male Fischer‐344 rats and New Zealand rabbits. Application sites were protected with nylon gauze and elastic bandage assemblies. Following application of measured amounts of radiolabeled dye in 0.1 M pH 10.2 carbonate buffer, serial urine and fecal samples were obtained from individual animals in metabolism cages at 24, 48, 72, 96, 120, and 144 h. Aliquots of urine and fecal homogenates were assayed for radioactivity by scintillation counting. Cumulative excretion of radioactivity from rats receiving DB38 was 0.05% of total dermal dose at 144 h in urine, and 0.16% of total dermal dose in feces. Cumulative excretion of radioactivity from DB38‐treated rabbits at 144 h was 3.12% of total dermal dose in urine, and 5.12% in feces. From rats and rabbits receiving topical DB19, cumulative excretion of radioactivity at 144 h was less than that from DB38‐treated animals. In rat urine, 0.04% of total dermal dose appeared; in rat feces, no radioactivity was recovered. In rabbit urine, 0.04% of dermal dose was found; 0.01% appeared in rabbit feces.

ISSN:0098-4108    

DOI:10.1080/15287398609530876

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

About 1200 urine samples were collected, mostly in winter seasons in 1982–1984, from adult women in 7 nonpolluted areas in widely separated parts of Japan, and analyses for cadmium (Cd‐U) were conducted in a single laboratory. The geometric mean (CM) by decades of age groups of Cd‐U, after adjustment for a specific gravity of urine of 1.016, increased from 0.88 μg/l in the twenties to reach a maximum of 1.78 μg/l in the fifties followed by gradual decrease to 1.31 μg/l in the eighties. The effect of smoking (about 8 cigarettes/d as a mean) was absent. Analyses of additional 125 urine samples from men revealed that Cd‐U in men was not higher than that in women. When classified geographically, Cd‐U was higher in the area on the coast of the Sea of Japan, as suspected in preceding studies on blood cadmium levels and dietary cadmium intakes. The Cd‐U levels observed in the present study are similar to the values in previous publications on the Japanese and are apparently higher than the counterpart values from Europe, the United States, and New Zealand.

ISSN:0098-4108    

DOI:10.1080/15287398609530877

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

Earthworms (Lumbriscus terrestris), collected from soils in southern Ontario, Canada, that had no previous history of cadmium application, contained 3 ppm cadmium. They were fed to Coturnix quail as 60% dry weight of their diet for 63 d to examine the extent of deposition of native cadmium. Cadmium in kidney, liver, and excreta was greatly elevated above that of birds fed a control diet without worms. No increase in the level of cadmium in eggs was found. The factors affecting the association of cadmium in soils and worms and their assimilation and possible toxic effects in foraging birds are discussed.

ISSN:0098-4108    

DOI:10.1080/15287398609530878

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

Telone II (technical grade, 1,3‐dichloropropene), a soil fumigant, was evaluated in chronic toxicology/carcinogenicity studies using Fischer‐344 (F344) rats and B6C3F, mice of both sexes. Doses administered were 0, 25, or 50 mg/kg to rats and 0, 50, or 100 mg/kg to mice. Telone II was given in com oil by gavage 3 times per week for 104 wk. Ancillary studies were conducted to determine time‐related effects, in which dose groups containing 5 male and 5 female rats were killed after receiving Telone II for 9, 16, 21, 24, or 27 mo. The primary organs affected were the forestomach (rats and mice), urinary bladder (mice), lung (mice), and liver (rats). Compound‐related non‐neoplastic lesions included basal‐cell or epithelial hyperplasia of the forestomach (rats and mice), epithelial hyperplasia of the urinary bladder (mice), and hydro‐nephrosis (mice). Neoplastic lesions associated with administration of Telone II included squamous‐cell papillomas of the forestomach (male and female rats, female mice), squamous‐cell carcinomas of the forestomach (Male rats, female mice), transitional‐cell carcinomas of the urinary bladder (female mice), alveolarlbronchiolar adenomas (female mice), and neoplastic nodules of the liver (male rats). Although cis‐ and trans‐1,3‐dichloropropene are the principal components of Telone II, the presence of 1% epichlorohydrin, a direct‐acting mutagen and carcinogen added as stablizer, may have subluenced the development of forestomach lesions. The results of the ancillary studies supported the findings of the carcinogenesis studies and demonstrated the time‐dependent development of lesions in the forestomach (basal‐cell hyperplasia and squamous‐cell papilloma). Under the conditions of these gavage studies, Telone II was shown to be carcinogenic in male and female F344 rats and female B6C3F1mice. Although the study in male B6C3F1mice was considered inadequate because of the low survival resulting from suppurative sublammation of the heart (myocarditis) in the control group, there was some indication of Telone ll‐re‐lated increases of transitional‐cell carcinomas of the urinary bladder, squamous‐cell papillomas of the forestomach, and alveolarlbronchiolar adenomas and carcinomas of the lung.

ISSN:0098-4108    

DOI:10.1080/15287398609530879

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

In vitro exposure of adult rat alveolar macrophages to either paraquat or diquat resulted in concentration dependent cytotoxicity (cell death). The herbicide paraquat, however was statistically significantly more potent toward these cells than was diquat. The LC50 value for paraquat (8‐h exposure, 37°C) was determined to be 0.94 mM [95% confidence interval (C.I.) 0.79–1.12 mM], whereas the corresponding LC50 value for diquat was 1.97 mM (C.I. 1.58–2.51 mM).

ISSN:0098-4108    

DOI:10.1080/15287398609530880

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

To evaluate the effect of straight‐chain alkanes on normal detoxication reactions, we studied the in vitro effect of the homologous series n‐hexane through n‐dodecane on two cytochrome P‐450 (EC 1.14.14.1) enzyme activities. Benzo[a]pyrene hydroxylase (BaPOHase) and 7‐ethoxycoumarin deethylase activities were measured in liver and lung microsomes of control and β‐naphthoflavone‐treated rats. In the presence of 2 mM n‐hexane through n‐dodecane, liver BaPOHase activity decreased from 67% of control with n‐dodecane to 21% of control with octane. Lung benzo[a]pyrene hydroxylase was insensitive to all tested alkanes at 2 mM. In the presence of 2 mM alkanes, liver 7‐ethoxycoumarin deethylase activity decreased from 73% of control with n‐octane to 28% with n‐octane. Lung 7‐ethoxycoumarin deethylase was also sensitive to the alkane series. In the presence of 2 mM alkane the greatest effect was obtained with n‐octane and represented a 56% loss in activity. Alkane concentration‐dependence measurements showed 0.02–0.20 mM as the sensitive region of the curve for n‐octane with maximal loss of activity achieved at 0.20 mM. Liver ethoxy‐coumarin deethylase activity from β‐naphthoflavone‐treated rats was less sensitive towards the reactive alkane, n‐octane, than the activity from control rats. Double‐reciprocal‐plot analysis revealed the maximal velocity (Vmax) was decreased in the presence of 0.2 mM n‐octane. Hence this hydrocarbon did not exert its effect solely as an alternate substrate. The data show the n‐alkanes, n‐hexane through n‐dodecane, interfered with a normal detoxication pathway in a manner that was chainlength‐depen‐dent, tissue‐specific, and dependent on the preexposure history of the animal.

ISSN:0098-4108    

DOI:10.1080/15287398609530881

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

Yohimbine was studied to examine its effectiveness in preventing central nervous system(CNS) depression and bradycardia induced by amitraz (N'‐(2,4‐dimethylphenyl)‐N‐[(2,4‐dimethylphenyl‐imino)‐methyl]‐N‐methyl‐methanimide). In control open‐field activity experiments, the dogs showed high numbers of grid‐line crossings in the first 5 min (exploratory phase), and subsequently low numbers of grid‐line crossings (nonexploratory phase). An iv injection of amitraz (1 mg/kg) abolished both the exploratory and nonexploratory phases and caused bradycardia. Yohimbine alone caused a trend to increase the open‐field activity in the nonexploratory phase. In addition, yohimbine prevented the bradycardia and suppression of open‐field activity induced by amitraz. The results suggest that yohimbine has a potential to be used as an antidote for amitraz overdose.

ISSN:0098-4108    

DOI:10.1080/15287398609530882

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

Benzyl chloride (BCL) is extensively used in industry for the manufacture of dyes, perfumes, and pharmaceutical products. A previous study from this laboratory revealed the presence of liver steatosis of the microvesicular type and central focal sublammation in rats following the inhalation of BCL. This study was conducted to investigate the hepatotoxicity of intravenous (iv) BCL in rat. BCL (250, 25, and 0 μg/kg) was administered (iv) to rats, and serum enzyme tests were used to evaluate hepatic injury. After 10 min from BCL administration, serum glutamic‐pyruvic transaminase and lactic dehydrogenase activities were significantly increased compared to the control group, while the values returned to normal within 7 h from the administration of BCL. Also, ornithine carbamyltransferase enzyme activity was significantly increased and reached a maximum as early as 0.5 h from the administration of BCL. Hepatic excretory function was investigated by the clearance of bromosulfophthalein (BSP) after 0.5 and 24 h from the administration of BCL. The clearance of BSP in both treatments was significantly slower compared to control group throughout the 24 h studied. Furthermore, BCL significantly decreased liver and blood glutathione values. This study revealed that BCL has the potential to cause hepatomalfunction.

ISSN:0098-4108    

DOI:10.1080/15287398609530883

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor