Ammonium thiocyanate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Quality of whole database:

Dermal absorption is lower than absorption via oral route. Testing via dermal route is therefore not preferred.

Additional information

For reproduction toxicity limited data is available. Studies focus on the possible goitrogen effects of thiocyanate. A 2 generation study in which the mothers are continuously fed 25 mg KSCN/rat/day from weaning (21 days age) via the diet (25 mg/rat at weaning ~ 1000 mg/kgbw/day; at adulthood about 100 mg/kg bw/day). After 8 weeks the KSCN fed rats became hypothyroid. and mating took place. Animals were kept on their respective diets throughout gestations and lactation. F1 females were kept at their mothers diets after weaning throughout subsequent pregnancy and lactation. The resulting F2 pups seemed normal and showed no differences in BW at birth or during weaning. However, T4 levels were markedly lower. Despite the relative high levels of thiocyanates, no obvious reproductive effects were observed. (Raghunath M & Bala TS, 1989, Neurochem. Int., Vol.33, pp:173-177)

 

From other studies it is probable that the compound has an adverse effect on the development the embryo: the effect on brain microtubuli formation and thyroid function occurred in conjunction with maternal effects. However, it is not possible to conclude that these effects in the offspring are specific developmental effects. Therefore, the data are insufficient to make a proposal for C&L and a specific NOAEL for developmental toxicity or reproduction toxicity cannot be derived. However, based on the available information is seems reasonable to assume that thiocyanate will not exert developmental or reproductive toxicity at when thyroid function is not impacted.

 

Offspring is naturally exposed during lactation as thiocyanate are excreted by the mammary glands for a functional use as substrate for peroxidise in milk. Various reports on thiocyanate measurements in breast milk report levels of thiocyanate between 1–5 mg/L. (Dorea JG, 2004, Maternal Thiocyanate and Thyroid Status during Breast-Feeding; J Am.Coll.Nutrit. 23(2), 97-101.)

Short description of key information:
All studies available for the aspect of reproductive toxicity are articles published in open literature. No GLP studies are available. None of the studies described in the publications is performed according to one of the OECD guidelines on reproductive toxicity (OECD 414, 415 or 416). Study design sometimes resembles those described the guidelines but none of the studies examined all the parameters requested to evaluate the effects on parents, foetuses andlor pups. Most studies focus only on the effect of thiocyanate on the thyroid function and on the development of the brain of neonates.

Justification for selection of Effect on fertility via oral route:
Justification: The data available do not allow a firm conclusion regarding the NOAEL for reproduction toxicity. Indications are at levels not leading to hypothyroidy, reproduction toxicity is unlikely. Based on the fact that humans are naturally exposed to thiocyanates by food further studies are not considered necessary. For further details see section 13 of the IUCLID5 and section 5.11 of the CSR.

Justification for selection of Effect on fertility via inhalation route:
The likelihood for exposure via inhalation is low. The vapour pressure of ammonium thiocyanate is very low (0.015 Pa, and probably much lower. See vapour pressure) and thus does not present any potential for inhalation exposure due to volatilization of the salt. Furthermore thiocyanates are very hygroscopic (see granulometry). Inhalable particles are not available and will also not be formed during handling and use of the substance.

Effects on developmental toxicity

Description of key information

All studies available for the aspect of reproductive toxicity are articles published in open literature. No GLP studies are available. None of the studies described in the publications is performed according to one of the OECD guidelines on developmental toxicity (OECD 414). Study design sometimes resembles those described the guidelines but none of the studies examined all the parameters requested to evaluate the effects on parents, foetuses and/or pups. Most studies focus only on the effect of thiocyanate on the thyroid function and on the development of the brain of neonates.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

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

See above under fertility.

For reproduction toxicity limited data is available. Studies focus on the possible goitrogen effects of thiocyanate. A 2-generation study with fixed dose levels in the food resulting to exposures of 100-1000 mg/kgbw for the females, resulted to hypothyroidy of the animals, but did not results in overt reproduction toxicity as judged by the normal body weights of the pups.

Although a standard guideline study for the assessment of developmental toxicity is lacking and thus no firm conclusion regarding the NOAEL for developmental toxicity can be made, and would basically also not be very informative as levels would also depend on iodine and thiocyanate levels in used feed, indications are that at levels not leading to hypothyroidy, reproduction toxicity is unlikely. Further studies are not expected to lead to additional relevant information.

 

Thiocyanate is a substance with a natural presence in the body, coming from intake via food (esp. cruciferae) and from detoxification of cyanide and nitriles.Natural background serum concentrations of thiocyanate found are 33.5 ± 25.4 µM for non-smokers and 111.2 ± 92.1 µM smokers (Tsuge, 2000), and after diner levels up to 160 µM of serum were seen (Eminedoki, 1994). 160 µM SCN- compares to 12 mg NH4SCN/L.

Additional confidence as to the lack of specific reproduction toxicity of thiocyanates can be provided by data derived from cyanide and cyanide salts. Of absorbed cyanide, 80% is metabolized to thiocyanate. In evaluating available data on cyanide salts for reproduction toxicity, the IPCS-CICAD evaluation on cyanides (2004) concludes “… it induces developmental effects only at doses or concentrations that are overtly toxic to the mothers.”

 

References:

- IPCS-CICAD:cyanides(2004)

- Weuffen W, et al., 2003, Thiocyanat - Ein biologisch aktives Ion von veterinärmedizinischer und medizinischer Relevanz [Thiocyanate--a biologically active ion of veterinary and medical relevance], Berl.Münch.Tierärtzl.Wschr. 116, 144-156.

- Tsuge K, et al., 2000, Cyanide and Thiocyanate Levels in Blood and Saliva of Healthy Adult Volunteers, J Health Science, 46(5) 343–350.

- Eminedoki DG et al., 1994, Thiocyanate levels of mainly dietary origin in serum and urine from a human population sample in Port Harcourt, Nigeria., Plant Foods Hum Nutr 46(4) 277-85.

Justification for selection of Effect on developmental toxicity: via oral route:
The data available do not allow a firm conclusion regarding the NOAEL for developmental toxicity. Indications are at levels not leading to hypothyroidy, developmental toxicity is unlikely. Based on the fact that humans are naturally exposed to thiocyanates by food further studies are not considered necessary. For further details see section 13 of the IUCLID5 and section 5.11 of the CSR.

Justification for selection of Effect on developmental toxicity: via inhalation route:
Justification: The likelihood for exposure via inhalation is low. The vapour pressure of ammonium thiocyanate is very low (0.015 Pa, and probably much lower. See vapour pressure) and thus does not present any potential for inhalation exposure due to volatilization of the salt. Furthermore thiocyanates are very hygroscopic (see granulometry). Inhalable particles are not available and will also not be formed during handling and use of the substance.

Justification for selection of Effect on developmental toxicity: via dermal route:
Justification: Dermal absorption is lower than absorption via oral route. Testing via dermal route is therefore not preferred.

Justification for classification or non-classification

Although standard guideline studies for the assessment of reproduction toxicity are lacking and thus no firm conclusion regarding the NOAEL for reproduction toxicity can be made, indications are that at levels not leading to hypothyroidy, reproduction toxicity is unlikely. Classification for reproduction toxicity is therefore not indicated.