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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
reproductive toxicity, other
Type of information:
experimental study
Adequacy of study:
supporting 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
Sex:
female
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.
Details on mating procedure:
no data
Analytical verification of doses or concentrations:
no
Details on analytical verification of doses or concentrations:
no data
Duration of treatment / exposure:
14 days before cohabitation and throughout pregnancy
Frequency of treatment:
daily
Details on study schedule:
14 days before cohabitation and throughout pregnancy
Doses / concentrations
Remarks:
Doses / Concentrations:
25 mg/kg bw/day
Basis:
nominal conc.
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.
Positive control:
no data

Examinations

Parental animals: Observations and examinations:
- number of matings
- vaginal smears
Oestrous cyclicity (parental animals):
no data
Sperm parameters (parental animals):
no data
Litter observations:
- number of young born per litter
- birth weights of the litter
Postmortem examinations (parental animals):
- gross pathology of ovaries and testes
Postmortem examinations (offspring):
- 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
Reproductive indices:
not given
Offspring viability indices:
not given

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not examined
Reproductive performance:
no effects observed

Details on results (P0)

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 (P0)

Key result
Dose descriptor:
NOAEL
Effect level:
25 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: no effects

Results: F1 generation

General toxicity (F1)

Mortality / viability:
no mortality observed

Details on results (F1)

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.

Overall reproductive toxicity

Key result
Reproductive effects observed:
no

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