Alterations of endocrine responses in male Sprague-Dawley rats following oral administration of methyl tert-butyl ether

Williams, TM; Cattley, RC; Borghoff, SJ

HERO ID

5929

Reference Type

Journal Article

Year

2000

Language

English

PMID

10746943

HERO ID 5929
In Press No
Year 2000
Title Alterations of endocrine responses in male Sprague-Dawley rats following oral administration of methyl tert-butyl ether
Authors Williams, TM; Cattley, RC; Borghoff, SJ
Journal Toxicological Sciences
Volume 54
Issue 1
Page Numbers 168-176
Abstract Methyl tert-butyl ether (MTBE) is an oxygenated fuel additive used to decrease carbon monoxide emissions during combustion. MTBE is a nongenotoxic chemical that induces Leydig cell tumors (LCT) in male rats. The mechanism of MTBE-induced LCT is not known; however, LCT induced by other nongenotoxic chemicals have been associated with the disruption of the hypothalamus-pituitary-testicular (HPT) axis. The objective of this study was to determine whether MTBE functions as an endocrine-active compound by affecting levels of specific hormones involved in the maintenance of the HPT axis. Nine-week-old male Sprague-Dawley rats were administered MTBE by gavage at 0, 250, 500, 1000, or 1500 mg MTBE/kg/day for 15 or 28 consecutive days and sacrificed 1 h following the last dose. Relative testis weights were increased only in high-dose animals treated for 28 days, and no testicular lesions were observed at any dose level. Adrenal gland, liver, and kidney weights were also increased. Histologic changes included protein droplet nephropathy of the kidney and centrilobular hypertrophy of the liver. Interstitial fluid and serum testosterone levels as well as serum prolactin levels were decreased only in animals treated with 1500 mg MTBE/kg/day for 15 days. At 28 days, serum triiodothyronine (T3) was significantly decreased at 1000 and 1500 mg MTBE/kg/day compared to control animals, and a decrease in serum luteinizing hormone and dihydrotestosterone was observed at 1500 mg MTBE/kg/day. These results indicate that MTBE causes mild perturbations in T3 and prolactin; however, the changes in testosterone and LH levels did not fit the pattern caused by known Leydig cell tumorigens.
Pmid 10746943
Wosid WOS:000085799400018
Is Certified Translation No
Dupe Override No
Comments ECRIB. 2000a in 0327,JC1. tert is italicized.Toxicol. Sci. 54: 168-176.
Is Public Yes
Language Text English
Keyword methyl tert-butyl ether (MTBE); Leydig cell tumors; hormonal feedback; hypothalamus-pituitary-testicular axis (HPT)
Relationship(s)