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Diss Factsheets

Toxicological information

Toxicity to reproduction: other studies

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Administrative data

toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
supporting study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study not conducted according to specific guidelines, but well-documented and accepted for publication in peer-reviewed literature

Data source

Reference Type:
Effect of ETBE on reproductive steroids in male rats and rat Leydig cell cultures.
de Peyster A, Stanard B, Westover C.
Bibliographic source:
Toxicol Lett. 2009 Oct 8; 190(1):74-80.

Materials and methods

Principles of method if other than guideline:
Study to investigate the effects of ETBE on reproductive steroids in male rats and rat Leydig cell cultures.
GLP compliance:
not specified
Type of method:
other: in vivo and in vitro

Test material

Constituent 1
Chemical structure
Reference substance name:
EC Number:
EC Name:
Cas Number:
Molecular formula:

Test animals

Fischer 344

Administration / exposure

Route of administration:
oral: gavage
corn oil
Duration of treatment / exposure:
2 weeks
Frequency of treatment:
Doses / concentrations
Doses / Concentrations:
600 mg/kg, 1200 mg/kg or 1800 mg/kg
actual ingested
No. of animals per sex per dose:
Control animals:
Details on study design:
Isolated rat Leydig cells were used to compare hCG-stimulated T production following exposure to ETBE, MTBE, and their common main metabolite, TBA.

In addition, male Fischer 344 rats were gavaged daily with 600 mg/kg, 1200 mg/kg or 1800 mg/kg ETBE in corn oil (n=12) for 14 days, the 1200 mg/kg dose chosen for comparison with a prior 14-day MTBE gavage experiment.

Results and discussion

Effect levels

Dose descriptor:
Effect level:
600 mg/kg bw/day
Basis for effect level:
other: Altered reproductive steroid levels in blood sampled 1h after treatment, only with doses that inhibit body weight gain. No evidence of androgen insufficiency in accessory organ weights and no testicular pathology in a subset (n=5) at 1800 mg/kg bw.

Observed effects

In vitro study:
In cell culture experiments, TBA was more potent than either ETBE or MTBE, both of which caused similar inhibition of T production at equimolar concentrations.

In vivo study
In the in vivo study, no significant plasma T reduction was seen 1h after the final 1200 mg/kg ETBE dose, whereas 1200 mg/kg MTBE had significantly lowered T when administered similarly to Sprague-Dawley rats. Some rats treated with 1800 mg/kg ETBE had noticeably lower T levels, and the group average T level was 66% of corn oil vehicle control (p>0.05) with high variability also evident in ETBE-treated rats. 17beta-Estradiol had been increased by 1200 mg/kg MTBE, and was elevated in the 1200 and 1800 mg/kg ETBE dose groups (p<0.05), both groups also experiencing significantly reduced body weight gain. None of these effects were seen with 600 mg/kg/day ETBE. No definitive evidence of androgen insufficiency was seen in accessory organ weights, and no testicular pathology was observed after 14 days in a small subset (n=5) of 1800 mg/kg ETBE-treated animals. Like MTBE, ETBE appears to be capable of altering reproductive steroid levels in peripheral blood sampled 1h after treatment, but only with extremely high doses that inhibit body weight gain and may produce mortality.

Applicant's summary and conclusion