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Description of key information

Based on data from acute toxicological studies and on physicochemical properties, high oral as well as inhalative absorption, but low dermal absorption can be expected for Guanidine hydrochloride.

Key value for chemical safety assessment

Additional information

No toxicokinetic studies are available for Guanidine hydrochloride. 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 hydrochloride is soluble in water and has a log P value of <-1.7, therefore absorption has to be expected. After oral exposure signs of systemic toxicity including death were observed in acute toxicity studies, thus absorption of Guanidine hydrochloride has obviously occurred. As a consequence it is likely that the substance will also be absorbed if it is inhaled. This assumption is supported by data from an acute toxicity study by inhalation route, were systemic effects were observed. As data from a dermal acute toxicity study show no systemic effects at the limit dose of 2000 mg/kg bw/d, Guanidine hydrochloride is expected to be not favourable for dermal absorption.

As outlined in the Guidance on information requirements and chemical safety assessment, Chapter R.7c 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. Dermal uptake for Guanidine hydrochloride is considered to be low, due to the water solubility of 2150 g/L and the log P value of <-1.7.

This is supported by Ertell (2006) who summarised that “there is limited evidence that guanidine is not absorbed to any significant degree through the skin in animals“.

In the acute oral toxicity study clear toxic signs to the central nervous system/neuromuscular system were observed, which indicate that the substance has been distributed to the CNS. The excretion route is expected to be via the urine, because Guanidine hydrochloride dissociates in body fluids into the corresponding ions, is highly water soluble and has a low molecular weight of 95.53 g/mol.

Guanidine hydrochloride is also used as pharmaceutical. According to prescribing information guanidine is indicated for the reduction of 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.”

The effect of Guanidine hydrochloride on energy metabolism was studied in rat liver, muscle and kidney: Intraperitoneal injection of 2.2 mmol/kg bw/d Guanidinium hydrochloride for 7 d altered the carbohydrate metabolism in rat liver, muscle and kidney by stimulating the glycolytic pathway (Rao et al 1992).

The chloride ion is a naturally occurring essential ion in animals as well as humans with well-known metabolism and mechanisms of action as described in standard textbooks on pharmacology and physiology.

Reference

Ertell K.: A Review of Toxicity and Use and Handling Considerations for Guanidine, Guanidine Hydrochloride, and Urea. Prepared for the U.S. Department of Energy under Contract DE-AC05-76RL01830