Hexanoic acid, 3,5,5-trimethyl-, tin(2+) salt (2:1)

Endpoint summary

Description of key information

Hexanoic acid, 3,5,5-trimethyl-, tin (2+) salt (2:1) is a tin-salt of an organic acid and is known to dissociate in aqueous medium. For the resulting tin moiety the absorption from gastrointestinal tract is reported to be low. 
The 3,5,5-trimethylhexanoate component, a branched-chain aliphatic fatty acid is reported to be rapidly absorbed from the gastrointestinal tract. From physico-chemical properties favourable absorption has to be expected and as a basic principle for these substances absorption after inhalation has to be assumed.  Moderate to high dermal absorption has to be expected based on water solubility and log P value. 

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

100

Absorption rate - inhalation (%):

100

Additional information

No toxicokinetic studies are available for hexanoic acid, 3,5,5-trimethyl-, tin (2+) salt (2:1). Assessment is based on available acute toxicity data, physicochemical properties and literature data and is developed with the aid of ECHA guidance on information requirements and chemical safety assessment chapter R7c.

Hexanoic acid, 3,5,5-trimethyl-, tin (2+) salt (2:1) is a tin-salt of an organic acid and is known to dissociate in aqueous medium, resulting in a tin II moiety and a 3,5,5-trimethylhexanoate component.

 

For the tin moiety the following is cited from the WHO evaluation report (WHO 2005, Tin and inorganic tin compounds: “In humans and laboratory mammals, absorption of inorganic tin from the gastrointestinal tract is low (generally less than 5%), but is influenced by dose, anion (compound solubility), and the presence of other substances. Unabsorbed ingested tin is mostly (95–99%) excreted in the faeces within 48 h. Absorbed tin distributes mainly to the bone, but also to the lungs, liver, and kidneys. Limited evidence suggests that inorganic tin does not readily cross the blood–brain barrier. Absorbed tin is mainly excreted in the urine, with some additional biliary excretion occurring. In mice, the biological half-life of absorbed inorganic tin was approximately 30 days.

 

The 3,5,5-trimethylhexanoate component, a branched-chain aliphatic fatty acid is rapidly absorbed from the gastrointestinal tract (Semino, 1998). Generally small molecules with molecular weights below 500 are favourable for absorption. As well for substances with Log P values between -1 and 4, favourable absorption by passive diffusion is assumed. The assumption is proven by the observed death in an acute oral toxicity study with hexanoic acid, 3,5,5-trimethyl-, tin (2+) salt (2:1) and further sustained by a similar acute oral toxicological profile of 3,5,5 - trimethylhexanonic acid. Both substances are classified according to GHS regulation in acute oral toxicity category 4.

The potential of generation of inhalable particles for hexanoic acid, 3,5,5-trimethyl-, tin (2+) salt (2:1) is negligible due to the low vapour pressure of 0.002 hPa. In general, in humans, particles with aerodynamic diameters below 100 μm have the potential to be inhaled. Particles with aerodynamic diameters below 50 μm may reach the thoracic region and those below 15 μm the alveolar region of the respiratory tract. However, if respirable particles are generated, absorption from the respiratory tract has to be expected. Absorption after inhalation has to be assumed as a basic principle, for substances absorbed after ingestion.

Considering the water solubility, moderate to high dermal absorption has to be expected, supported by a Log P value between 1 and 4, favouring dermal absorption. However, the observed effects in toxicity studies indicate low dermal absorption. In an acute dermal toxicity study with hexanoic acid, 3,5,5-trimethyl-, tin (2+) salt (2:1) no clinical signs or mortality were observed after dermal exposure of limit dose of 2000 mg/kg bw under occlusive conditions, while mortalities were observed at the same dose after oral ingestion.

Following absorption the dissociation product 3,5,5-trimethylhexanoate will enter common distribution and metabolic pathways, which are considered similar among mammals. Beta-oxidation of 3-methyl-branched fatty acids is blocked by the 3-methyl-group which prevents the dehydrogenation step. Instead 3-methyl-branched fatty acids undergo alpha-oxidation in peroxisomes resulting in the formation of a 2-methyl-branched fatty acid shortened by one carbon atom and formyl-CoA which is subsequently converted to formate and CO2 (Casteels, 2003). After a further beta-oxidation step, degradation of 3,5,5-trimethylhexanoic acid finally results in 2,2-dimethylpropanoic acid containing a tertiary carbon atom which cannot be further degraded, but is conjugated with glucuronic acid and excreted into bile and urine (Dziewiatkowski, Lewis, 1944).