Registration Dossier

Toxicological information

Developmental toxicity / teratogenicity

Currently viewing:

Administrative data

Endpoint:
developmental toxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study was conducted to assess teratogen effects before establishment of a guideline. Sufficient data is provided to determine that its conclusion is valid.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1982
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Principles of method if other than guideline:
Method: other. Predates guideline
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
IUCLID 4 Test Substance: as prescribed by 1.1 - 1.4

Test animals

Species:
rat
Strain:
Sprague-Dawley

Administration / exposure

Route of administration:
oral: gavage
Details on exposure:
Rats were dosed at a constant volume of 5 ml/kg.
Frequency of treatment:
daily (gd 6 through 15)
No. of animals per sex per dose:
25
Control animals:
yes, concurrent vehicle
Details on study design:
sex: female
duration of test: 9 days

Examinations

Maternal examinations:
Clinical observations were performed daily and body weights recorded on gd 0, 6, 10, 12, 16 and 20.
Ovaries and uterine content:
At scheduled necropsy on gd 20, dams were sacrificed and the implantation sites evaluated (number and location of viable and non-viable fetuses, early and late resorptions and number of total implantations and corpora lutea), abdominal and thoracic cavities were examined for grossly evident morphological changes.
Fetal examinations:
Fetuses were removed, weighed, sexed, tagged and examined for soft tissue malformations using the method of Wilson (Teratology-Principles and techniques Univ. Chicago Press, Chicago, IL 262-277 1965). Remaining fetuses were eviscerated, fixed and stained for subsequent skeletal
examination by a method similar to that described by Dawson (Stain Technol. 1 123-124, 1926).

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
observed at 1 mg/kg bw/d

Effect levels (maternal animals)

Key result
Dose descriptor:
NOAEL
Effect level:
1 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:no effects

Effect levels (fetuses)

Key result
Dose descriptor:
NOAEL
Effect level:
10 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: teratogenicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Key result
Developmental effects observed:
no

Any other information on results incl. tables

Survival of the dams was 100% for the control and all treatment groups. The antemortem and necropsy observations for treated groups was comparable to those for control groups.  Signs of maternal toxicity was evident by slight
reduction in body weight gain, during the overall treatment and gestation periods (days 6 to 15 and 0 to 20
respectively), in the 3 and 10 mg/kg/day group.  Statistically significant differences in corpora lutea/dam
and total implantation/dam ratios occurred between the 10 mg/kg/day and control groups. However, because these were
pretreatment parameters they were not considered compound related.  

Fetal deaths at 10 mg/kg/day.  The viable fetus/dam, post implantation losses/dam, mean fetal body
weight and fetal sex distribution in the 10 mg/kg/day group and all cesarean section observation parameters for the 1
and 3 mg/kg/day dosage groups were comparable with controls.  The incidence of fetal malformations and developmental
variations was comparable between test and control groups.  Acetone cyanohydrin did not elicit a teratogenic response
when administered by the oral route to Charles River rats at 10 mg/kg/day.

Applicant's summary and conclusion

Conclusions:
Timed-pregnant rats were dosed with acetone cyanohydrins (0, 1, 3 and 10 mg/kg bw/d, at a constant volume of
5 ml/kg. Group sizes consisted of 25 animals and 25 litters were examined per group (no premature deaths). Clinical
observations were performed daily and body weights recorded on gd 0, 6, 10, 12, 16 and 20. At scheduled necropsy on gd
20, dams were sacrificed and the implantation sites evaluated (number and location of viable and non-viable fetuses, early
and late resorptions and number of total implantations and corpora lutea), abdominal and thoracic cavities were
examined for grossly evident morphological changes. Fetuses were removed, weighed, sexed, tagged and examined for soft
tissue malformations using the method of Wilson (1965). Remaining fetuses were eviscerated, fixed and stained for subsequent skeletal
examination by a method similar to that described by Dawson (1926).

Survival of the dams was 100% for the control and all treatment groups. The antemortem and necropsy observations
for treated groups were comparable to those for control groups. Signs of maternal toxicity was evident by slight
reduction in body weight gain, during the overall treatment and gestation periods (days 6 to 15 and 0 to 20
respectively), in the 3 and 10 mg/kg/day group. Statistically significant differences in corpora lutea/dam
and total implantation/dam ratios occurred between the 10 mg/kg/day and control groups. However, because these were
pretreatment parameters they were not considered compound related. Fetal deaths at 10 mg/kg/day. The viable
fetus/dam, post implantation losses/dam, mean fetal body weight and fetal sex distribution in the 10 mg/kg/day group
and all cesarean section observation parameters for the 1 and 3 mg/kg/day dosage groups were comparable with controls.
The incidence of fetal malformations and developmental variations was comparable between test and control groups.
Acetone cyanohydrin did not elicit a teratogenic response when administered by the oral route to Charles River rats at
10 mg/kg/day.