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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:
other information
Study period:
1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards.

Data source

Reference
Reference Type:
publication
Title:
Effects of Dimethoxyethyl phtalate, Monomethoxyethyl phtalate, 2-Methoxyethanol and Methoxyacetic acid on post implantation rat embryos in culture
Author:
Yonemoto J, Brown NA, Webb M
Year:
1984
Bibliographic source:
Toxicology Letters, 21: 97-102.

Materials and methods

Principles of method if other than guideline:
Embryo culture system based on New (1978, Biol. Rev., 53: 81-122).
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
Methoxyacetic acid (MMA) obtained from Aldrich Chemical Co. Ltd. (Gillingham, Dorset). No purity is indicated. MAA-Na was prepared based on the parent substance and used for testing.

Test animals

Species:
rat
Strain:
Wistar

Administration / exposure

Details on mating procedure:
Nulliparous female rats of the Wistar-Porton strain were mated overnight with males of the same strain (Day 0 of gestation represented the morning following mating). On Day 9 of gestation (embryonic age 9.5 days) rat conceptuses were removed aseptically and collected. The intact visceral yolk sacs and ectoplacental cones were retained, but Reichert's membranes were removed.
Frequency of treatment:
Rat conceptuses were transferred in pairs into 40-ml bottles that contained male rat serum (3 ml) and either MEM (1 ml; controls) or soIutions in this medium (1 ml) of the test compound.
Duration of test:
The cultures were grown in the absence of antibiotics for 46 h in gas phases with 5% (v/v) carbon dioxide at 37.5 ± 0.5°C. At the end of the culture period, rat conceptuses were transferred to Ringer's Solution and examined.
Doses / concentrations
Remarks:
Doses / Concentrations:
1, 2, 3, 4 mM
Basis:
nominal conc.

Examinations

Statistics:
Growth of the embryos was estimated by crown-rump and head length measurements. The degree of differentiation and development was evaluated by a morphological scoring system. The significance of the results was assessed by Student's t test.

Results and discussion

Results (fetuses)

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Rat embryos aged 9.5 days were incubated in vitro (in culture medium) for 46 hours. Malformations of the yolk sac, auditory pits, somites and neural groove were evident at concentrations of 1 mM Methoxyacetic acid (=90 µg/ml) and above. From 2 mM Methoxyacetic acid (=180 µg/ml), there was a significant decrease in the yolk sac diameter, the length from head to rump and the length of the skull (n=12). A reduced number of somites was found, too. All of the embryos (n=10) showed developmental anomalie(s) at a concentration of 5 mM (=451 µg/ml).

Applicant's summary and conclusion

Executive summary:

In post-implantation rat embryonic cultures Methoxyacetic acid (1 - 5 mmol/L; 90 - 450 mg/l) interfered with normal growth and development of the early neurula stage. The NOEC was 1 mmol/L (Yonemoto et al, 1984).