Two-year drinking water carcinogenicity study of methyl tertiary-butyl ether (MTBE) in Wistar rats

被引:11
作者
Dodd, Darol [1 ]
Willson, Gabrielle [2 ]
Parkinson, Horace [1 ]
Bermudez, Edilberto [1 ]
机构
[1] Hamner Inst Hlth Sci, Res Triangle Pk, NC 27709 USA
[2] EPL North Carolina, Res Triangle Pk, NC 27709 USA
关键词
MTBE; drinking water; Wistar; chronic progressive nephropathy; carcinogenicity; CHRONIC PROGRESSIVE NEPHROPATHY; HUMAN RISK-ASSESSMENT; FISCHER-344; RATS; EXPOSURE; MICE; TOXICITY; GASOLINE; TESTS;
D O I
10.1002/jat.1776
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Methyl tertiary-butyl ether (MTBE) has been used as a gasoline additive to reduce tailpipe emissions and its use has been discontinued. There remains a concern that drinking water sources have been contaminated with MTBE. A two-year drinking water carcinogenicity study of MTBE was conducted in Wistar rats (males, 0, 0.5, 3, 7.5mgml1; and females, 0, 0.5, 3, and 15mgml1). Body weights were unaffected and water consumption was reduced in MTBE-exposed males and females. Wet weights of male kidneys were increased at the end of two years of exposure to 7.5mgml1 MTBE. Chronic progressive nephropathy was observed in males and females, was more severe in males, and was exacerbated in the high MTBE exposure groups. Brain was the only tissue with a statistically significant finding of neoplasms. One astrocytoma (1/50) was found in a female rat (15mgml1). The incidence of brain astrocytomas in male rats was 1/50, 1/50, 1/50 and 4/50 for the 0, 0.5, 3 and 7.5mgml1 exposure groups, respectively. This was a marginally significant statistical trend, but not statistically significant when pairwise comparisons were made or when multiple comparisons were taken into account. The incidence of astrocytoma fell within historical control ranges for Wistar rats, and the brain has not been identified as a target organ following chronic administration of MTBE, ethyl tert-butyl ether, or tertiary butyl alcohol (in drinking water) to mice and rats. We conclude that the astrocytomas observed in this study are not associated with exposure to MTBE. Copyright (c) 2011 John Wiley & Sons, Ltd.
引用
收藏
页码:593 / 606
页数:14
相关论文
共 46 条
[1]  
[Anonymous], 1999, IARC MON EV CARC RIS
[2]  
[Anonymous], 1996, GUIDE CARE USE LAB A, DOI DOI 10.17226/5140
[3]   TESTS FOR LINEAR TRENDS IN PROPORTIONS AND FREQUENCIES [J].
ARMITAGE, P .
BIOMETRICS, 1955, 11 (03) :375-386
[4]   EFFECTS OF TREATMENT-INDUCED MORTALITY AND TUMOR-INDUCED MORTALITY ON TESTS FOR CARCINOGENICITY IN SMALL SAMPLES [J].
BAILER, AJ ;
PORTIER, CJ .
BIOMETRICS, 1988, 44 (02) :417-431
[5]   METHYL-TERTIARY-BUTYL ETHER (MTBE) - A GASOLINE ADDITIVE - CAUSES TESTICULAR AND LYMPHOHAEMATOPOIETIC CANCERS IN RATS [J].
BELPOGGI, F ;
SOFFRITTI, M ;
MALTONI, C .
TOXICOLOGY AND INDUSTRIAL HEALTH, 1995, 11 (02) :119-149
[6]   Toxicity of methyl tertiary-butyl ether (MTBE) following exposure of Wistar Rats for 13 weeks or one year via drinking water [J].
Bermudez, Edilberto ;
Willson, Gabrielle ;
Parkinson, Horace ;
Dodd, Darol .
JOURNAL OF APPLIED TOXICOLOGY, 2012, 32 (09) :687-706
[7]  
Bird MG, 1997, J APPL TOXICOL, V17, pS45, DOI 10.1002/(SICI)1099-1263(199705)17:1+<S45::AID-JAT410>3.3.CO
[8]  
2-B
[9]   Physiologically based pharmacokinetic rat model for methyl tertiary-butyl ether; comparison of selected dose metrics following various MTBE exposure scenarios used for toxicity and carcinogenicity evaluation [J].
Borghoff, Susan J. ;
Parkinson, Horace ;
Leavens, Teresa L. .
TOXICOLOGY, 2010, 275 (1-3) :79-91
[10]   A 24-month dietary carcinogenicity study of DAG in mice [J].
Chengelis, CP ;
Kirkpatrick, JB ;
Bruner, RH ;
Freshwater, L ;
Morita, O ;
Tamaki, Y ;
Suzuki, H .
FOOD AND CHEMICAL TOXICOLOGY, 2006, 44 (01) :122-137