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Description of key information

Key value for chemical safety assessment

Absorption rate - oral (%):
50
Absorption rate - dermal (%):
25
Absorption rate - inhalation (%):
100

Additional information

No ADME and dermal absorption studies with guanidine carbonate are available.

However, a series of acute toxicity studies give an indication about the bioavailability after oral and dermal application. In three acute and one repeated dose oral toxicity studies with guanidine carbonate systemic toxicity was seen leading to the conclusion that the test substance is bioavailable after oral application.

After dermal application of 2000 mg test substance/kg bw in a rat acute toxicity study and dermal application in two guinea pig sensitization studies no systemic effects could be observed. The octanol/water partition coefficient of -1.63 (20 °C) indicates the highly hydrophilic property of the substance. Therefore, it is assumed that the dermal absorption of guanidine carbonate is rather low.

Vaporisation is deemed negligible as the vapour pressure will be clearly <10^-10 Pa as guanidine carbonate is a solid ionic crystal. Therefore, inhalation exposure is only possible via aerosols of solid particles or dissolved material.

In the body the salt guanidine carbonate is dissociated to guanidine. Guanidino compounds, including guanidine are considered to be metabolic products of protein catabolism. In the body guanidine is well distributed with the plasma and after injected in the mice intraperitoneally linear increase in brain concentration is found (D`Hooge et al., 1992) indicating that there is no blood brain barrier. Due to the high water solubility and the low partition coefficient accumulation in fatty tissues is unlikely. Guanidine is not further metabolized and excreted unchanged via renal clearance (Sawynok et al., 1972).

Following absorption values were taken into account:

-       Inhalation: 100 % (worst case assumption)

-       Oral: 50% (this can be considered as a conservative value, based on the comparison between the LD50subcutaneous versus oral in rats for Guanidine, which is at least 3 times lower); currently in the dossier 50% absorption after oral application was described.

-       Dermal: 25% (this can be considered as a conservative value, based on the comparison between the LD50oral versus dermal in rats for Guanidine carbonate and Guanidine chloride, which is at least 2 times lower).

References:

D’Hooge R., Pei Y.-Q., Marescau B., De Deyn P.P. (1992); Convulsive action and toxicity of uremic guanidino compounds: behavioral assessment and relation to brain concentration in adult mice. Journal ofNeurological Sciences, 112, 92-105.

Sawynok J., Dawborn J.K. (1972); Plasma concentration and urinary excretion of guanidine derivates in normal subjects and patients with renal failure. Clinical and Experimental Pharmacology and Physiology, 2, 1-15.

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