Guanidinium thiocyanate

Endpoint summary

Description of key information

No toxicokinetic studies are available for Guanidine Thiocyanate. Assessment is based on available acute toxicity data and physicochemical properties and is developed with the aid of ECHA guidance on information requirements and chemical safety assessment chapter R7c.

 

Guanidine Thiocyanate is soluble in water (1562 g/L) and has a log P value of <-1.5, therefore absorption has to be expected. After oral exposure signs of systemic toxicity including death were observed in an acute toxicity study, thus absorption of Guanidine Thiocyanate has obviously occurred.

In this study clear signs of the central nervous/neuromuscular system were observed, which indicate that the substance has been distributed to the CNS. Further acute toxicity data are not available for Guanidine Thiocyanate.

 

As a consequence of absorption after oral exposure it is likely that the substance will also be absorbed if it is inhaled. This assumption is supported by read-across data from an acute toxicity study by inhalation route with Guanidine Hydrochloride, were systemic effects were observed.

 

The stratum corneum provides its greatest barrier function against hydrophilic compounds. If water solubility is above 10,000 mg/L and the log P value below 0 the substance may be too hydrophilic to cross the lipid rich environment of the stratum corneum (refer to TGD R7c).

Based on physico-chemical properties dermal uptake of Guanidine Thiocyanate is expected to be low, due to the water solubility of 1562 g/L and the log P value of <-1.5. However, Guanidine Thiocyanate is corrosive and damage to the skin surface may enhance penetration. Therefore for safety assessment the dermal absorption of corrosive concentrations is presumed to be 100 %, which pose a worst-case.

 

The excretion route is expected to be via the urine, because Guanidine Thiocyanate dissociates in body fluids into the corresponding ions, is highly water soluble and has a low molecular weight of 118 g/mol.  

 

Guanidine hydrochloride is used as pharmaceutical. According to prescribing information:

“Guanidine is indicated for the reduction of the symptoms of muscle weakness and easy fatigability associated with the myasthenic syndrome of Eaton-Lambert.” The clinical pharmacology is described as follows: “Guanidine apparently acts by enhancing the release of acetylcholine following a nerve impulse. It also appears to slow the rates of depolarization and repolarization of muscle cell membranes.” ¹

 

The Thiocyanate ion is rapidly and almost completely absorbed, with wide extracellular distribution. Excretion is primarily via urine. Small amounts are excreted in expired air and faeces. Thiocyanate is secreted via mammary and salivary glands and gastric mucosa, where it serves as a substrate for peroxidase in milk, saliva and gastric juice. Elimination half-life is 3 days.²

 

“Thiocyanate is a potent inhibitor of iodide transport and is a competitive substrate for the thyroid peroxidase, but it does not appear to be concentrated in the thyroid. Blockage of the iodide trapping mechanism has a disruptive effect on the thyroid-pituitary axis, similar to iodine deficiency. The blood levels of T4 and T3 decrease, resulting in a compensatory increase in the secretion of TSH by the pituitary gland. The hypertrophy and hyperplasia of follicular cells following sustained exposure results in an increased thyroid weight and the development of goiter.“³

 

According to information from substance evaluation of Ammonium Thiocyanate ”…thiocyanates do not impair the activities of the thyroid gland itself. Thiocyanates only reduce the entry of iodide ions into the thyroid gland via competitive anion inhibition. In this manner, the subsequent reaction chain is limited due to lack of iodine compounds (including lack of hormones T3 and T4). However, thiocyanates do not directly affect these reactions neither enter into them nor block them. The only consequence is a limited intake of iodine. From the foregoing it can be concluded that the actual activity of the thyroid gland is not affected by thiocyanates, so from this point of view it is not an endocrine disrupting effect according to the definition of WHO(1). The eMSCA concludes that based on the available information, the concern for endocrine disruption is not confirmed.”⁴

 

 

References:

 

1.     GUANIDINE HYDROCHLORIDE Tablets, Merck & Co., INC, 2015;

available at: https://www.merck.com/product/usa/pi_circulars/g/guanidine_hydrochloride/guanidine_pi.pdf

 

2.     EFSA, Conclusion on the peer review of the pesticide risk assessment of the active substance potassium thiocyanate, EFSA Journal 2013;11(6):2922

available at: http://onlinelibrary.wiley.com/doi/10.2903/j.efsa.2013.2922/epdf

 

3.     Handbook of Toxicologic Pathology,Wanda M. Haschek, ‎Colin G. Rousseaux, 2013

 

4.     Substance Evaluation Conclusion document Ammonium Thiocyanate, 01 August 2016, Evaluating Member State(s): Czech Republic, EC No. 217-175-6,

available at: https://echa.europa.eu/documents/10162/58ca02ce-e82b-4ea2-8e18-73ee35858391

 

 

 

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

100

Absorption rate - inhalation (%):

100