Short-term inhalation test for evaluating industrial hepatotoxicants in rats

Brondeau, M. T.; Bonnet, Pierre; Guenier, J. P.; Céaurriz, J. de

doi:10.1016/0378-4274(83)90274-6

Cited by 20 publications

(9 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is suggested that the DMF-induced necrotic damage to the hepatocytes as evidenced by the increased incidences of the single cell necrosis and focal necrosis in the 13-wk exposure study is causally related to the release of cytolytic enzymes such as AST, ALT and LDH into the serum. The present findings confirm the previously reported results 10,13,15,16,19,20) indicating that AST and ALT were increased by exposures of rats to DMF. Furthermore, it has been widely recognized that serum levels of AST and ALT are increased among factory workers exposed to DMF [3][4][5][6][7][8][9] .…”

Section: Disucussionsupporting

confidence: 93%

“…Medical case reports and epidemiological studies on the health of DMF-exposed workers revealed that the liver was primarily damaged together with various complaints, alcohol intolerance and the release of liver cytolytic enzymes into the plasma 1,[3][4][5][6][7][8][9] . Experimental toxicology of DMF demonstrated that the primary liver lesion was characterized by necrosis, degeneration, hepatocellular hypertrophy, mitotic figures and altered serum activities of liver enzymes [10][11][12][13][14][15][16][17][18][19][20] . Inhalation and dermal exposures to DMF are principal routes for workers, because DMF is very volatile and permeable through the skin 7,9,21,22) .…”

mentioning

confidence: 99%

See 1 more Smart Citation

Toxicity due to 2‐ and 13‐wk Inhalation Exposures of Rats and Mice to N, N‐Dimethylformamide

Senoh

Katagiri

Arito

et al. 2003

Journal of Occupational Health

View full text Add to dashboard Cite

Toxicity due to 2-and 13-wk Inhalation E x p o s u r e s o f R a t s a n d M i c e t o N , NDimethylformamide: Hideki SENOH, et al. Japan Bioassay Research Center, Japan Industrial Safety and Health Association-In order to better characterize the toxicity of N,N-dimethylformamide (DMF) and to provide its basic toxicity data for risk assessment of workers exposed to DMF, F344 rats and BDF 1 mice of both sexes were exposed by inhalation (6 h/d × 5 d/wk) to 100, 200, 400, 800 or 1,600 ppm DMF for 2 wk, and 50, 100, 200, 400 or 800 ppm DMF for 13 wk. Three male and 7 female rats died during the 2-wk exposure to 1,600 ppm DMF, but no death of the exposed rats or mice occurred under any other exposure conditions. Massive, focal and single cell necroses were observed in the liver of DMF-exposed rats and mice. The massive necrosis associated with the centrilobular fibrosis occurred at the highest exposure concentration. The single cell necrosis was associated with fragmentation of the nucleoli as well as an increased mitotic figure. The 13-wk exposures of rats and mice to DMF were characterized by increases in the relative liver weight and the incidence of the centrilobular hepatocellular hypertrophy as well as increased serum levels of AST, ALT, LDH, total cholesterol and phospholipid. Lower confidence limits of the benchmark dose yielding the response with a 10% extra risk (BMDL 10 ) were determined for the relative liver weight and the incidence of hepatocellular hypertrophy of the 13-wk exposed animals. The BMDL 10 resulted in 1 ppm for the increased relative liver weight of male rats and mice and 17 ppm for the hepatocellular hypertrophy of male mice. (J Occup Health 2003; 45: 365-375)

show abstract

Section: Disucussionsupporting

confidence: 93%

mentioning

confidence: 99%

Toxicity due to 2‐ and 13‐wk Inhalation Exposures of Rats and Mice to N, N‐Dimethylformamide

Senoh

Katagiri

Arito

et al. 2003

Journal of Occupational Health

View full text Add to dashboard Cite

show abstract

“…This scenario is consistent with existing data. The P450 inactivation would explain the decrease in serum sorbitol dehydrogenase and glutamate dehydrogenase activities seen after multiple exposures compared to a single exposure (26). Reid et al (22) showed that o-DCB treatment produced covalent binding to rat liver protein at dosages that did not produce liver necrosis, a finding in agreement with our decrease in P450 at dosages lower than those at which necrosis and transaminase increases became evident.…”

Section: Discussionsupporting

confidence: 84%

The differential hepatotoxicity and cytochrome P450 responses of fischer‐344 rats to the three isomers of dichlorobenzene

Allis¹,

Simmons²,

House³

et al. 1992

J. Biochem. Toxicol.

View full text Add to dashboard Cite

The acute hepatotoxicity and response of hepatic cytochrome P450 to treatment with the three isomers of dichlorobenzene (DCB) have been investigated. The objectives were to estimate the onset of toxicity and to further elucidate the role of cytochrome P450 in the metabolism and toxicity of these compounds. In a study design employing one animal per dose level, Fischer-344 rats were gavaged with up to 25 different dosages, then evaluated 24 h later. Hepatic necrosis, serum alanine aminotransferase, and serum aspartate aminotransferase exhibited similar patterns demonstrating that ortho-DCB (o-DCB) was the most toxic in terms of both earliest onset and degree of response at higher dosages. For these three endpoints, meta-DCB (m-DCB) exhibited a lesser toxicity. Para-DCB (p-DCB) did not cause changes in these three endpoints, but hepatic degenerative changes were found. Total hepatic cytochrome P450 responses were also different after treatment with each isomer. The o-DCB produced a dose-dependent decrease in P450 beginning at dosages lower than the onset of necrosis and appeared to be a suicide substrate for P450. The m-DCB treatment increased P450 at dosages below the onset of necrosis and decreased P450 at higher dosages, with the decline preceding the onset of hepatocyte death. Treatment with p-DCB increased P450 beginning at 380 mg/kg. The combination of toxicity and P450 profiles has provided a framework for interpreting literature data on the metabolism and toxicity of the DCBs in rats. It is also noteworthy that o-DCB and p-DCB were administered at dosages several times the oral rat LD-50 (RTECS) without any lethality.

show abstract

“…Medical case reports have revealed that while ingestion of DCE affects the stomach, liver, kidney, lung, heart and central nervous system 6) , inhalation of DCE causes irritation and inflammation of the respiratory tract, damage to the lung, liver and kidneys, and death due to cardiac toxicity 7) . Experimental toxicology studies showed that DCE primarily affects the liver, kidneys and respiratory system 1,5,[8][9][10][11][12][13][14] . Five cohort studies examining the risk of cancer among workers with potential exposure to DCE were not able to link the excesses of cancer incidence to occupational exposure to DCE [15][16][17][18][19] .…”

mentioning

confidence: 99%

Carcinogenicity and Chronic Toxicity in Rats and Mice Exposed by Inhalation to 1,2‐Dichloroethane for Two Years

Nagano

Umeda

Senoh

et al. 2006

Journal of Occupational Health

View full text Add to dashboard Cite

Carcinogenicity and Chronic Toxicity in Rats and Mice Exposed by Inhalation to 1,2-Dichloroethane for Two Years: Kasuke NAGANO, et al. Japan Bioassay Research Center, Japan Industrial Safety and Health AssociationCarcinogenicity and chronic toxicity of 1,2-dichloroethane (DCE) were examined by inhalation exposure of groups of 50 F344 rats and 50 BDF1 mice of both sexes to DCE vapor or clean air as control for 6 h/d, 5 d/wk and 104 wk. The rats were exposed to 10, 40 or 160 ppm (v/v) DCE, while the mice were exposed to 10, 30 or 90 ppm. The 2-yr exposure to DCE produced a dose-dependent increase in incidences of benign and malignant tumors, including subcutaneous fibroma, mammary gland fibroadenoma and peritoneal mesothelioma in male rats; subcutaneous fibroma and mammary gland adenoma, fibroadenoma and adenocarcinoma in female rats; and bronchiolo-alveolar adenoma and carcinoma, endometrial stromal polyp, mammary gland adenocarcinoma and hepatocellular adenoma in female mice. No exposure-related change in the incidence of non-neoplastic lesions or in any hematological, blood biochemical or urinary parameter occurred in any DCE-exposed rat or mouse group. The types of tumors and their target organs found in this study were consistent with those observed in rats and mice administered DCE by gavage in a NCI study. Selection of the exposure concentrations was considered appropriate with reference to the maximum tolerated dose for the highest doses and an occupational exposure limit of DCE for the lowest dose. The present findings suggest that those carcinogenic responses be primarily considered for standard setting of occupational and environmental exposure to DCE. (J Occup Health 2006; 48: 424-436)

show abstract

Short-term inhalation test for evaluating industrial hepatotoxicants in rats

Cited by 20 publications

References 13 publications

Toxicity due to 2‐ and 13‐wk Inhalation Exposures of Rats and Mice to N, N‐Dimethylformamide

Toxicity due to 2‐ and 13‐wk Inhalation Exposures of Rats and Mice to N, N‐Dimethylformamide

The differential hepatotoxicity and cytochrome P450 responses of fischer‐344 rats to the three isomers of dichlorobenzene

Carcinogenicity and Chronic Toxicity in Rats and Mice Exposed by Inhalation to 1,2‐Dichloroethane for Two Years

Contact Info

Product

Resources

About