Metformin hydrochloride

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the physicochemical and toxicological properties suggest no potential for a significant rate of absorption through the skin

Justification for type of information:

The octanol water distribution coefficient (logP) provides a first estimate on the skin penetration and thus the dermal exposure of a given chemical. The logP is a constant defined as the ratio of equilibrium concentrations of a chemical dissolved in a two-phase immiscible system consisting of water and octanol. A log P of 0 describes a compound that is equally soluble in organic and aqueous media. A logP of 1 indicates a 10:1 solubility ratio of the chemical in the organic:aqueous phase. The solubility ratio of a chemical with a log P value of −1 is 1:10 in the organic:aqueous phase.
Consequently, chemicals with negative log P values are more soluble in aqueous media than in organic solvents and will partition to the aqueous instead of the lipophilic phase. Metformin HCl has a logP at -3.5, i.e. clearly below 0.
The stratum corneum consists of approximately 40% water (Warner et al., 1988). Therefore, octanol serves as a simplified model of the stratum corneum. For log P, a threshold of zero determines the percutaneous penetration behaviour. The logP of Metformin is clearly below this threshold indicating that a dermal absorption can be excluded. Therefore no systemic exposure can be assumed after dermal administraion and thus there is no need for further studies on acute dermal toxicity.