Registration Dossier

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
unsuitable test system

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Teratogenicity and embryolethality of acrolein and structurally related compounds in rats
Author:
Slott VL and Hales BF
Year:
1985
Bibliographic source:
Teratology 32: 65-72
Reference Type:
secondary source
Title:
Propionaldehyde. BUA-Stoffbericht 195
Author:
Beratergremium für umweltrelevante Altstoffe (BUA)
Year:
1996
Bibliographic source:
S. Hirzel Wiss. Verl.-Ges. 1997, Stuttgart

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Intra-amniotic injection on day 13 of gestation. On day 20 of gestation dams were killed and fetuses were removed and analysed.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Canada, Inc. (St. Constant, Quebec, Canada)
- Age at study initiation: no data
- Weight at study initiation: 225 - 250 g
- Fasting period before study: no data
- Housing: no data
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

Administration / exposure

Route of administration:
other: intraamniotic injection
Vehicle:
other: 0.9% NaCl
Details on exposure:
On day 13 of gestation, the pregnant rats were laparotomized under ether anesthesia and the uteri were exposed. Embryos in one uterine horn received a 10 µl intraamniotic infection, using a 30-gauge hydodermic needle. Contralateral embryos were uninjected. Following injections the uterus was repositioned in the abdominal cavity and the laparotomy was closed with two layers of interrupted nylon sutures.
Analytical verification of doses or concentrations:
no
Details on mating procedure:
- Impregnation procedure: purchased timed pregnant
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy
Duration of treatment / exposure:
injection on day 13 of gestation
Frequency of treatment:
single dose
Duration of test:
7 days, rats were killed on day 20 of gestation
Doses / concentrationsopen allclose all
Dose / conc.:
10 other: µg/fetus (nominal)
Dose / conc.:
100 other: µg/fetus (nominal)
Dose / conc.:
1 000 other: µg/fetus (nominal)
No. of animals per sex per dose:
6 for 10µg/fetus and 100µg/fetus, respectively
5 for 1000µg/fetus
18 for control group
Control animals:
yes, concurrent no treatment
yes, sham-exposed
Details on study design:
Sex: female
Duration of test: 20 days

Examinations

Maternal examinations:
no data
Ovaries and uterine content:
no data
Fetal examinations:
- External examinations: Yes: all per litter
- Soft tissue examinations: No
- Skeletal examinations: Yes: all per litter
- Head examinations: Yes: all per litter

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:not examined

Results (fetuses)

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

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Propionaldehyde caused a dose-dependent increase of the mortality and absorption rate which amounted to ca. 50 % (p<0.05) at 1000 µg/fetus. A dose-dependent increase of dead or absorbed fetuses (ca. 24 % in the 1000 µg-group) also occurred on the corresponding contralateral uterus side, but the value still lay in the deviation range of the controls. The mortality and absorption rate in the control group was ca. 24 % (injection of physiological saline solution) and amounted to 12 % on the contralateral uterus side. Only one of the fetuses treated with 1000 µg showed a malformation (shortened tail; data unavailable on the number of fetuses examined). In the control group, malformations occurred in 6 % of the fetuses treated with physiological saline solution and in 3 % of the untreated contralateral fetuses (type of malformations unspecified).

Applicant's summary and conclusion