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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP; guideline study
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test (OECD 422)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
purity: 99.9%

Test animals

Species:
rat
Strain:
Wistar
Details on test animals and environmental conditions:
Male and female Wistar rats, strain Crl:WI(Han), supplied by Charles River Laboratories, Research Models and Services, UK

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure (if applicable):
nose/head only
Vehicle:
air
Details on exposure:
For each concentration the test substance was supplied to a two-component atomizer at a constant rate by means of an infusion pump. The aerosol was generated with compressed air mixed with conditioned dilution air and passed into the inhalation system.
Analytical verification of doses or concentrations:
yes
Details on mating procedure:
Each of the male and female animals was mated overnight in a 1:1 ratio for a maximum of 2 weeks. Throughout the mating period, each female animal was paired with a predetermined male animal from the same test group. Mating was accomplished by placing the female in the cage of the male mating partner from about 16.00 h until 07.00-09.00 h of the following morning. Deviations from these specified times were possible on weekends and public holidays and were reported in the raw data. A vaginal smear was prepared after each mating and examined for sperm. If sperm was detected, pairing of the animals was discontinued. The day on which sperm was detected was denoted "gestation day (GD) 0" and the following day "GD 1".
Duration of treatment / exposure:
6 hours
Frequency of treatment:
daily
Duration of test:
females: 46-48 days
males: 29 days
Doses / concentrations
Remarks:
Doses / Concentrations:
0; 3.88±0.63; 16.6±3.1; 41.2±6.5 mg/m3
Basis:
analytical conc.
No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
local toxic effects on the nasal cavity due to corrosive properties of the test substance

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEC
Effect level:
40 mg/m³ air
Based on:
test mat.
Basis for effect level:
other: developmental toxicity
Dose descriptor:
NOAEC
Effect level:
40 mg/m³ air
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEC
Effect level:
4 mg/m³ air
Based on:
test mat.
Basis for effect level:
other: maternal toxicity

Results (fetuses)

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

Effect levels (fetuses)

open allclose all
Dose descriptor:
NOAEC
Effect level:
40 mg/m³ air
Based on:
test mat.
Basis for effect level:
other: teratogenicity
Dose descriptor:
NOAEC
Effect level:
40 mg/m³ air
Based on:
test mat.
Basis for effect level:
other: embryotoxicity
Dose descriptor:
NOAEC
Effect level:
40 mg/m³ air
Based on:
test mat.
Basis for effect level:
other: fetotoxicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The NOAEC for developmental toxicity in male and female Wistar rats was 40 mg/m³ (highest dose tested).
Executive summary:

2-(2-Aminoethoxy)ethanol was administered via inhalation to groups of 10 male and 10 female Wistar rats (F0 animals) at concentrations of 4, 16, and 40 mg/m³. The mean number of delivered pups per dam and the rate of liveborn and stillborn pups were evenly distributed among the test groups (control, 4, 16 and 40 mg/m³). The respective values reflect the normal range of biological variation inherent in the strain used in this study. The viability index as indicator for pup mortality between PND 0-4 varied between 99% and 100% in all test groups. The sex distribution and sex ratios of live F1 pups on the day of birth and on PND 4 did not show biologically relevant differences between the test groups. The F1 pups did not show any test substance-induced or spontaneous clinical signs up to scheduled sacrifice on PND 4. Mean pup body weights and pup body weight changes of all test substance-treated groups were generally comparable to the concurrent control group throughout the lactation period. Some F1 pups showed spontaneous findings at necropsy, such as post mortem autolysis, aneurysm of ductus arteriosus, short innominate, empty stomach and hemorrhagic testis. These pup necropsy findings occurred without relation to dosing and/or can be found in the historical control data at comparable or even higher incidences. Therefore, these findings were not considered to be associated to the test substance. Thus, the NOAEC for developmental toxicity was 40 mg/m3.