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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:
supporting 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:
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
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

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
Remarks:
Study was subject to quality control procedures.
Limit test:
yes

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
Specific details on test material used for the study:
Source: Olin Corporation, New Haven, Connecticut, USA.
Purity: 99.9%.
Storage temp: 20C.
Note: Impurities not specified but likely to be higher oligomers of series such as tetraethylene glycol butyl ether.

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: individually; stainless steel mesh bottom floor polypropylene cages until GD18 then in solid bottom cages with paper bedding from GD18 for nesting. Bedding not then changed until end of study to avoid disturbance of litter.
- Diet and water: commercial rodent diet (Special Diet Services, Witham, UK) and water (filtered and sterilised tap water) ad libitum. Analysis of water performed to check for impurities.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-23
- Humidity (%): 43-63
- Air changes (per hr): 15-25
- Photoperiod (hrs dark / hrs light): 12/12.

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 - taken as day 1.
- Pregnant animals delivered to test laboratory over a 3 day period. No further information
Duration of treatment / exposure:
Days 7 - 16 of gestation inclusive.
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 / concentrationsopen allclose all
Dose / conc.:
250 mg/kg bw/day (actual dose received)
Dose / conc.:
1 000 mg/kg bw/day (actual dose received)
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
- Random allocation of animals to cages and treatment groups.

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 (within 24 hours) and 5: viability, sex, number, litter weight.

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not examined
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined

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)

Dose descriptor:
NOEL
Remarks on result:
not determinable due to absence of adverse toxic effects

Results (fetuses)

Fetal body weight changes:
no effects observed
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed
Reduction in number of live offspring:
no effects observed
Changes in sex ratio:
not examined
Changes in litter size and weights:
no effects observed
Changes in postnatal survival:
no effects observed
External malformations:
not examined
Skeletal malformations:
not examined
Visceral malformations:
not examined
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.

Effect levels (fetuses)

Dose descriptor:
NOAEL
Remarks on result:
not determinable due to absence of adverse toxic effects

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
no

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. Based on the criteria of the screening protocol this substance would not be deemed to have developmental toxicity potential.