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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:
1988-1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study, but older study and only part of report available

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: EPA, Washington, D.C. Federal Register. Friday. September 27, 1985. Vol. 50 No. 188, 40 CFR Part 798 Part 4900. Toxic Substance Control Act Test Guidelines: Final Rules.
Deviations:
no
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: Crl:CD®(SD)BR Presumed Pregnant Rats

Administration / exposure

Route of administration:
dermal
Vehicle:
unchanged (no vehicle)
Details on exposure:
TEST SITE
- Area of exposure: 7 x 5 cm
- Type of wrap if used:an aluminium foil patch (covering at least the shaved dorsal area of dosage application) that will be held in place by a medical-type adhesive bandag (e.g. Poroplast®).
- Time intervals for shavings or clipplings: Shaving will be repeated as necessary throughout the dosage period.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped with water
- Time after start of exposure:6 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): sham, 0.517, 1.551 and 3.619 g/kg/day
- Concentration (if solution):pure
- Constant volume or concentration used: no



USE OF RESTRAINERS FOR PREVENTING INGESTION: Each rat was fitted with an Elizabethan collar.
Analytical verification of doses or concentrations:
no
Details on mating procedure:
There were 25 presumed pregnant rats in each group.
Duration of treatment / exposure:
Ethyl lactate was applied percutaneously to the rats once daily for a six-hour exposure period on days 6 through 15 of gestation.
Frequency of treatment:
Ethyl lactate was applied percutaneously to the rats once daily for a six-hour exposure period on days 6 through 15 of gestation.
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0 g/kg/day
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
0.517 g/kg/day
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
1.551 g/kg/day
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
3.619 g/kg/day
Basis:
nominal conc.
No. of animals per sex per dose:
25 presumed pregnant rats/group
Control animals:
yes, sham-exposed

Examinations

Maternal examinations:
Day 0 of presumed gestation was defined as the day spermatozoa were identified in a smear of the vaginal contents or a copulatory plug was found insitu. Each rat was observed aily during teh dosage and postdosage periods for evidence of skin reactions and other clinical signs of test substance effects., including death, abortion, premature delivery, body weight and feed consumption.

One low dosage group dam was inadvertently sacrificed on day 18 of gestation. All other dams were sacrificed and necropsied on day 20 of presumed gestation. Maternal tissues with gross lesions present wer retainde in neutral bufferd 10% formalin. The liver of each dam was weighed.
Ovaries and uterine content:
The uterine contents were examined for implantations, early and late resoprtions, and live and dead fetuses. Corpora lutea were counted for each ovary.
Fetal examinations:
Fetuses were evaluated for viability, body weight, sex and gross external morphology. Approximately one-half of the fetuses in each litter were fixed in Bouin's solution prior to visceral evaluation (Wilson's sectioning). The remaining fetuses in each litter wer eviscerated, fixed in alcohol and processed for skeletal evlutation (alizarin red S staining).

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
The highest dosage (3.619 g/kg/day) caused slight erythema and/or desquamation more frequently than these signs occurred in sham control group rats. These skin observations may have been interrelated with incidental hyperactivity that occurred for one high dosage group rat. The incidences of thes skin and clinical observations were not statistically significant,as compared with the sham control group value.

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Effect level:
> 1 551 - < 3 619 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
> 3 619 mg/kg bw/day
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:
No adverse effects on embryo-fetal viability, body weight or morphology were observed.

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Ethyl lactate is minimally toxic to pregnant rats at the highest dosage that could be tested (3.619 g/kg/day) and at this maximum dosage is not a developmental toxicant.
Executive summary:

In a developmental toxicity study ethyl lactate was administered to 25 female Crl:CD®(SD)BR presumed pregnant rats /dose applied percutaneously at dose levels of 0, 0.517, 1.551 and 3.619 g/kg/day from days 6 through 15 of gestation.

Percutaneously application of ethyl lactate to pregnant rats at the highest The highest dosage that could be given (3.619 g/kg/day) caused slight erythema and/or desquamation more frequently than these signs occurred in sham control group rats. These skin observations may have been interrelated with incidental hyperactivity that occurred for one high dosage group rat. The incidences of thes skin and clinical observations were not statistically significant,as compared with the sham control group value. The maternal LOAEL is 3.619 g/kg/day, based on slight erythema and/or desquamation. The maternal NOAEL is > 1.551 and < 3.619.

No adverse effects on embryo-fetal viability, body weight or morphology were observed. The developmental NOAEL is 3.619 g/kg/day.