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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Reasonably well-documented study which meets basic scientific principles.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1986
Reference Type:
publication
Title:
Triethylene glycol ethers: Evaluation of in vitro absorption through human epidermis, 21 day dermal toxicity in rabbits and a developmental screen in rats
Author:
Leber AP, Scott RC, Hodge MCE, Johnson D, Krasavage WJ
Year:
1990
Bibliographic source:
J Am Coll Toxico, 9 (5) 507-15

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Chernoff-Kavlock assay
Deviations:
yes
Remarks:
modified for use with rats rather than mice
Principles of method if other than guideline:
The modified assay has also been shown to respond to known teratogens by a variety of routes of administration and has been verified by NIOSH (Schuler) and in the testing laboratory itself
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): triethylene glycol monobutyl ether (TEGBE)
- Physical state: Clear, colorless liquid
- Analytical purity: 99.9+%
- Other: Source: Olin Corporation, New Haven, Connecticut, USA

Test animals

Species:
rat
Strain:
other: Alpk: AP (Wistar-derived)
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Specific Pathogen Free colony, maintained at the Animal Breeding Unit, Imperial Chemical Industries PLC, Alderley Park, UK
- Age at study initiation: 11 - 13 weeks of age
- Weight at study initiation: 210 - 305 g
- Housing: solid bottom cages with paper bedding from GD18.
- Diet and water: commercial rodent diet and water ad libitum

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
deionised water
Details on exposure:
Test material was administered in deionised water at a dosing volume of 10ml/kg bodyweight (lml/100g).
Analytical verification of doses or concentrations:
no
Details on mating procedure:
- Impregnation procedure: cohoused
- If cohoused:
- Proof of pregnancy: sperm in vaginal smear.
- Pregnant animals delivered to test laboratory over a 3 day period. No further information
Duration of treatment / exposure:
Days 7 - 16 of gestation
Frequency of treatment:
Once daily at the same time each day
Duration of test:
Maternal animals and offspring were sacrificed on day 5 post partum
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 250 mg/kg or 1000 mg/k
Basis:
nominal in water
No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: The maximum dose levels of TEGBE was selected base on the maximum recommended in OECD and EPA guidelines

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

BODY WEIGHT: Yes
- Time schedule for examinations: Day 1 and subsequent weights recorded on Days 7 - 17, 19 and 22 of gestation and on Day 5 post partum
Ovaries and uterine content:
The uteri of females which failed to litter were grossly examined for implantation sites on or shortly after Day 25 of gestation to ascertain if the animals had been pregnant
Indices:
Litter data collected on post partum days 1-5: viability, sex, number, litter weight.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
No significant changes in clinical condition were seen throughout the study in females treated with TEGBE. No maternal mortality was observed in the study. Slight maternal toxicity was observed in both EGME groups (increased incidence of piloerection) and in the top dose group, several instances of vaginal bleeding between Days 17 and 19 of gestation were recorded, this condition is often observed with foetal resorption

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
There were no effects on the litter parameters measured in the TEGBE-treated groups at either the 250 mg/kg or 1000 mg/kg dose levels

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Administration of the positive control (methoxyethanol - EGME) produced complete resorption of all embryos at both dose levels and there are signs that EGME may have produced slight maternal toxicity at both dose levels.

Applicant's summary and conclusion

Conclusions:
At the dose levels tested (250 or 1000mg/kg/day), 2-(2-(2-butoxyethoxy)ethoxy)ethanol showed no foetotoxic or teratogenic potential and exhibited no maternal toxicity
Executive summary:

In a GLP developmental toxicity screening study in rats, the test substance when administered by gavage on gestation days 7 -16 at doses of 250 or 1000 mg/kg/day showed no foetotoxic or teratogenic potential and exhibited no maternal toxicity.