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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
Study period:
1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: public available literature (non GLP, non Guideline) Read across to sodium cyanate. For justification of read across see endpoint summary.

Data source

Reference
Reference Type:
publication
Title:
Pharmacology of cyanate. II. Effects on the endocrine system
Author:
Graziano, J.H.; Thornton; Y. S.; Leong, J. K.; Cerami, A.
Year:
1973
Bibliographic source:
Journal of pharmacology and experimental therapeutics, Vol. 185, No. 3, page 667-675

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Public available literature. No guideline indicated. For details on method see materials and methods section.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
no details given

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals and environmental conditions:
Source: Holtzman Company (Madison, Wisconsin, USA)
weight: 200-250 g

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
water
Details on exposure:
Adult female rats were injected i.p. with 25 mg/kg bw/day of sodium cyanate (0.154 M) for 14 days before cohabitation and throughout pregnancy. Control rats received an equivalent amount of NaCl.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
no data
Details on mating procedure:
no detail given.
Duration of treatment / exposure:
14 days before cohabitation and throughout pregnancy
Frequency of treatment:
daily
Duration of test:
14 days before cohabitation and throughout pregnancy
No. of animals per sex per dose:
8 females per treatment group
Control animals:
yes, plain diet
Details on study design:
no further detail given.

Examinations

Maternal examinations:
- number of matings
- number of young born per litter
- birth weights of the litter
- vaginal smears
Ovaries and uterine content:
- gross pathology of ovaries and testes
Fetal examinations:
- gross pathology:
Twenty newborn rats from each group were chosen at random and sacrificed with ether. Skeletal whole mounts were prepared by the alizarin red method (Dawson, 1926).
Statistics:
mean and standard deviation
Indices:
not given
Historical control data:
not given

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
Two groups of female rats were injected with 25 mg/kg bw/day of either sodium cyanate or NaCl for 14 days before cohabitation and throughout pregnancy. A normal four or five day estrus cycle was observed in all animals prior to mating. There were no significant differences in the number of successful matings.

Effect levels (maternal animals)

Key result
Dose descriptor:
NOAEL
Effect level:
25 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: overall effects

Results (fetuses)

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

Details on embryotoxic / teratogenic effects:
No differences in number of young per litter or the birth weights of the pups. In addition, there were no gross or skeletal abnormalities of the young of the cyanate-injected animals.

Effect levels (fetuses)

Key result
Dose descriptor:
NOAEL
Effect level:
25 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: overall effects

Overall developmental toxicity

Key result
Developmental effects observed:
no

Any other information on results incl. tables

In a developmental toxicity study sodium cyanate was administered to 8 female Sprague-Dawley rats/dose i.p. at dose levels of 0 and 25 mg/kg bw/day.

Two groups of female rats were injected with 25 mg/kg bw/day of either sodium cyanate or NaCl for 14 days before cohabitation and throughout pregnancy. A normal four or five day estrus cycle was observed in all animals prior to mating. There were no significant differences in the number of successful matings.

The maternal LOAEL can not be determined as no effects occurred. The maternal NOAEL is 25 mg/kg bw/day.

No differences in number of young per litter or the birth weights of the pups were observed. In addition, there were no gross or skeletal abnormalities of the young of the cyanate-injected animals.

The developmental LOAEL can not be determined as no effects occurred. The developmental NOAEL is 25 mg/kg bw/day.

The developmental toxicity study in the rat is classified acceptable.

Applicant's summary and conclusion

Conclusions:
The i.p. administration of 25 mg/kg bw/day of sodium cyanate to rats had no effect on reproductive capacity and was not teratogenic.
Executive summary:

In a developmental toxicity study sodium cyanate was administered to 8 female Sprague-Dawley rats/dose i.p. at dose levels of 0 and 25 mg/kg bw/day.

Two groups of female rats were injected with 25 mg/kg bw/day of either sodium cyanate or NaCl for 14 days before cohabitation and throughout pregnancy. A normal four or five day estrus cycle was observed in all animals prior to mating. There were no significant differences in the number of successful matings. The maternal LOAEL can not be determined as no effects occurred. The maternal NOAEL is 25 mg/kg bw/day.

No differences in number of young per litter or the birth weights of the pups were observed. In addition, there were no gross or skeletal abnormalities of the young of the cyanate-injected animals. The developmental LOAEL can not be determined as no effects occurred. The developmental NOAEL is 25 mg/kg bw/day.

The developmental toxicity study in the rat is classified acceptable.