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EC number: 213-030-6 | CAS number: 917-61-3
- Life Cycle description
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- Endpoint summary
- Appearance / physical state / colour
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- Endpoint summary
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- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
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- Toxicological Summary
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Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Description of key information
The available studies are used as supporting
information.
The increase in oxygen affinity produced by exchange transfusing of
pregnant rats with blood that had been treated previously with sodium
cyanate caused reduction of fetal body and liver weight. This was shown
by two independent studies with similar experimental design.
To fulfill the REACH requirements of Annex X, section 8.7.3, an extended one-generation reproductive toxicity study that has been proposed with the structural analogue potassium cyanate will be used as read across source after availability of the results.
In aqueous solution cyanate salts dissociate very quickly to cyanate ion and the respective alkali metal ion. It is not expected that Na+ or K+ contribute to the reproduction/developmental toxicity of cyanates as both represent basic metal ions present in the human body in high concentrations.
Effect on fertility: via oral route
- Endpoint conclusion:
- no study available (further information necessary)
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
In a reproduction toxicity study (Graziano, 1973) 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 therefore >=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 after i.p. administration is therefore >= is 25 mg/kg bw/day.
In a fertility toxicity study (Graziano, 1973) sodium cyanate was administered to 6 females C57 BL/6J mice/dose in diet at dose levels of 0 and 1 % corresponding to 0 and 1500 mg/kg bw/day. The feeding of a 1 % cyanate diet to paired mice immediately before or at various times during pregnancy did not affect the number of successful mating, the number of young born per litter or the birth weights of the litter. The cyanate fed females did not have further pregnancies; in fact, the mice did not have further pregnancies as long as they were maintained on the 1 % cyanate diet. This block in reproductive capacity was reversible since normal pregnancies and litters were observed when the animals were switched to a regular diet. Daily examination of vaginal smears revealed that in contrast to the control mice which had a four day estrus cycle, mice receiving a 1% sodium cyanate diet had prolonged periods of anestrus and came into estrus only occasionally and sporadically. Histopathological examination revealed no lesions in the ovaries or testes of the animals receiving the 1 % cyanate diet. The maternal LOAEL is 1500 mg/kg bw/day. The maternal NOAEL could not be derived as effects occurred in the single dose tested. There were no gross abnormalities of the young. The number of young weaned per litter was reduced in those mice which had receiving cyanate for 14 days or more before parturition. The developmental LOAEL is 1500 mg/kg bw/day, based on reduced number of pups. The maternal NOAEL could not be derived as effects occurred in the single dose tested.
Effects on developmental toxicity
Description of key information
No adverse effects on developmental toxicity were observed for sodium cyanate in two studies. In the first (i.p. administration, rat) no adverse effects on reproduction and maternal toxicity were observed at all up to a concentration of 25 mg/kg bw/day (highest concentration investigated). In the second study conducted with mice also no effects on developmental toxicity were observed. However, it was observed that the females were not able to get pregnant again as long as they were maintained on a high 1 % cyanate diet (1500 mg/kg bw/day). This effect is regarded to be related to reproduction toxicity (fertility) and not to developmental toxicity most likely due to observed systemic toxicity at this dose (see also repeated dose toxicity). In two additional studies (see toxicity to reproduction: other studies) adverse effects on development were observed, but these effects were considered of secondary nature due to hemoglobin damage of the parental animals.The biological relevance of these effects will be investigated/clarified in the proposed extended one-generation reproductive toxicity study.
Link to relevant study records
- 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.
- 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
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- Source: Holtzman Company (Madison, Wisconsin, USA)
weight: 200-250 g - 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.
- 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
- 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. - Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 25 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: overall effects
- 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. - Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 25 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: overall effects
- Key result
- Developmental effects observed:
- no
- 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.
Reference
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.
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 25 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- acceptable
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Key study:
In a developmental toxicity study (Graziano, 1973) 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 allows the preliminary conclusion, that sodium/potassium cyanate does not present developmental toxicity.
Supporting study:
In a developmental toxicity study (Graziano, 1973) sodium cyanate was administered to 6 females C57 BL/6J mice/dose in diet at dose levels of 0 and 1 % corresponding to 0 and 1500 mg/kg bw/day.
The feeding of a 1 % cyanate diet to paired mice immediately before or at various times during pregnancy did not affect the number of successful mating, the number of young born per litter or the birth weights of the litter. The cyanate fed females did not have further pregnancies; in fact, the mice did not have further pregnancies as long as they were maintained on the 1 % cyanate diet. This block in reproductive capacity was reversible since normal pregnancies and litters were observed when the animals were switched to a regular diet. Daily examination of vaginal smears revealed that in contrast to the control mice which had a four day estrus cycle, mice receiving a 1% sodium cyanate diet had prolonged periods of anestrus and came into estrus only occasionally and sporadically. Histopathological examination revealed no lesions in the ovaries or testes of the animals receiving the 1 % cyanate diet. The maternal LOAEL is 1500 mg/kg bw/day, based on block in reproductive capacity. The maternal NOAEL could not be derived as effects occurred in the single dose tested.
There were no gross abnormalities of the young. The number of young weaned per litter was reduced in those mice which had receiving cyanate for 14 days or more before parturition. The developmental LOAEL is 1500 mg/kg bw/day, based on reduced number of pups. The maternal NOAEL could not be derived as effects occurred in the single dose tested.
The developmental toxicity study in the mouse is classified acceptable as supporting study.
Toxicity to reproduction: other studies
Description of key information
In two additional studies (see toxicity to reproduction: other studies) adverse effects on development were observed, but these effects were considered of secondary nature due to hemoglobin damage of the parental animals.
Additional information
- The effects of an acute increase of the oxygen affinity of maternal blood in pregnant rats on fetal weight, fetal brain and liver weights, placental weight and the hematocrit of the fetal blood were examined (Bauer, 1981). The increase in oxygen affinity was produced by exchange transfusing of pregnant rats on day 19 of gestation with blood that had been treated and modified previously with sodium cyanate. As a result of the exchange transfusion, the difference in oxygen affinity between maternal and fetal blood essentially disappeared causing an artificial situation. Pregnant rats exchanged with normal blood served as controls. On day 21 of gestation, the fetal body weight and the fetal liver weight were significantly smaller by 18% and 25% respectively, in the group where the oxygen affinity of the maternal blood was acutely raised when compared to the controls causing a lower support of the pups with oxygen. Also, the hematocrit of the fetal blood was significantly higher in the group where mothers had the high blood oxygen affinity. Placental weight and fetal brain weight were not significantly altered. The authors infer, that the reduction of fetal weight is due to fetal hypoxia which is caused by the abolishment of the difference in oxygen affinity between maternal and fetal blood, cause by sodium cyanate.
This study is not considered relevant for the hazard assessment of cyanate as effects were noted only secondary due to hemoglobin damage of parenteral animals and due to the artificial test conditions.
- Pregnant rats were exchange transfused (Hebbel et al., 1980) with homologous blood on the ninth day of gestation, the experimental group receiving donor blood having P50 of about 15 mm Hg achieved by prior incubation with sodium cyanate (50 mM). This changed mean maternal p50 from 41.1 to 24.6 mm Hg; the normal prenatal rat has P50 = 23.7 mm Hg due to low erythrocyte 2,3-DPG content. Parameters reflecting the adequacy of fetal oxygenation were examined on the 20th and 21st days of gestation and at term (22 days). Fetuses from the experimental group were significantly smaller on the 21st day and at term, and this was accompanied by placental hypertrophy. There was no significant difference in fetal weight on the 20th day of gestation unless a second exchange transfusion was performed to further lower maternal P50. There was a trend towards erythrocytosis in the experimental group fetuses. It is concluded that a narrowing of the P50 difference between mother and fetus caused by sodium cyanate has adverse effects on fetal wellbeing in the rat.
This study is not considered relevant for the hazard assessment of cyanate as effects were noted only secondary due to hemoglobin damage of parenteral animals and due to the artificial test conditions.
Justification for classification or non-classification
No sufficient data on reproductive toxicity is available so far for sodium cyanate. An extended one-generation reproductive toxicity study is proposed for the analogue substance potassium cyanat, which will be used as read across source after availability.
In accordance with annex VI of CLP (Regulation (EC) No 1272/2008) sodium cyanate has not to be classified regarding reproduction toxicity laying down the principles of GHS. In conclusion, as far as no other data is available sodium cyanate is not classified regarding reproduction/developmental toxicity according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.
Additional information
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.

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