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Developmental toxicity / teratogenicity

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developmental toxicity
Type of information:
experimental study
Adequacy of study:
supporting study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Acceptable, well documented publication which meets basic scientific principles. It should be pointed out that maternal mortality was 30% and that the tested dose was not suitable for evaluating toxicity. No examination of malformations was performed in the pups.

Data source

Reference Type:

Materials and methods

Principles of method if other than guideline:
In this screening developmental toxicity test with a total of 60 chemicals, pregnant mice were dosed with the respective test substance during Days 6-13 of pregnancy and then allowed to deliver litters. The number of liveborn pubs, their birth weight, and their growth and survival until Day 3 of age were used as indices of potential developmental toxicity.
GLP compliance:

Test material

Constituent 1
Chemical structure
Reference substance name:
2-methoxyethyl acrylate
EC Number:
EC Name:
2-methoxyethyl acrylate
Cas Number:
Molecular formula:
2-methoxyethyl acrylate
Details on test material:
- Name of test material (as cited in study report): Glycol, ethylene, monomethyl ether acrylate
- Physical state: liquid
- Analytical purity: no data

Test animals

Details on test animals or test system and environmental conditions:
- Source: Charles River Breeding Laboratories
- Age at study initiation: 6-8 weeks
- Housing: time-mated mice were housed singly in solid-bottom boxes with nesting material, which was changed weekly. No bedding change was made later than GD 17 to avoid disturbing mice near parturition.
- Diet: standard diet (supplier not further specified for each chemical), ad libitum
- Water: ad libitum
- Acclimation period: ca. 5 days for dose-finding animals

- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
other: distilled water
Details on exposure:
- Amount of vehicle (if gavage): 10 mL/kg bw
Analytical verification of doses or concentrations:
Details on mating procedure:
- Impregnation procedure: purchased timed pregnant
- Proof of pregnancy: vaginal plug referred to as Day 0 of pregnancy
Duration of treatment / exposure:
Day 6-13 of gestation
Frequency of treatment:
daily, 7 days/week
Duration of test:
up to 19 days; Day 3 post-partum
No. of animals per sex per dose:
50 P females
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: dose levels was based on a preliminary dose-finding study, in which 10 virgin females per group received the test substance once daily at 5 different dose levels for 8 consecutive days. The animals were observed for mortalities and clinical signs of toxicity during a period of 8 days post-treatment. Based on the outcome of the study, the predicted LC10 value (650 mg/kg bw) was selected as dose level for treatment in the developmental toxicity screening test.


Maternal examinations:
- Time schedule: animals were observed for clinical signs of toxicity and mortality twice daily during treatment (GD 6-13) and once daily on GD 14-17. Beginning on GD 18, mice were observed twice daily for signs of parturition.

- Sacrifice on Day 3 post-partum
- Organs examined: the uteri of animals, which failed to deliver, were examined for the presence of implantation sites as evidence of early termination of pregnancy.
Ovaries and uterine content:
The uterine content was examined after termination: Yes
Examinations included:
- Number of implantations: Yes
- Number of early resorptions: Yes
Fetal examinations:
- External examinations: No
- Soft tissue examinations: No
- Skeletal examinations: No
- Head examinations: No
The Statistical Analysis System (SAS Institute Inc., Cary, NC, USA) was used to analyse data of individual parameters. Body weights on GD 6 were analysed by two-tail ANOVA to verify that there were no group differences in the initial body weight. Mortality (excluding deaths attributed to doing errors) was contrasted between pregnant and nonpregnant mice by two-tail Fisher’s exact test. Nonpregant mice were excluded from all subsequent analysis. One-tail Fisher’s exact test was used to compare the proportion of pregnant survivors with viable litters (at least 1 liveborn pup) to the concurrent vehicle control. For mice that delivered a viable litter, maternal body weight change from GD 6 to PD (postnatal day) 3, the number of liveborn pups per litter. Percent neonatal survival to PD 3, average pub weight at birth, and average pup weight gain by PD 3 were analysed by pairwise multiple comparisons of control and treated groups using a two-tail Mann-Whitney U-test.
- Liveborn pups per litter
- Percentage of neonatal survival until PD 3
- Birth weight per pup
- Weight gain per pup from PD 0 to PD 3

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
The test substance induced deaths in 15/50 dams, corresponding to a mortality rate of 30%.

Effect levels (maternal animals)

Dose descriptor:
dose level: 650 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:yes

Details on embryotoxic / teratogenic effects:
The number of litters was reduced in treated dams (14 litters) compared to control dams (28 litters). No liveborn pubs were observed in any of the 14 litters of the treated dams. This effect was significantly different from the control group, which had 25 viable litters compared to a total of 28 litters. Overall, the test substance adversely affected all measures of reproductive success, since no liveborn pubs were recorded.

Effect levels (fetuses)

Dose descriptor:
dose level: 650 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: fetotoxicity

Fetal abnormalities

not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion