3,3,5-trimethylcyclohexyl acrylate

Endpoint summary

Description of key information

No experimental toxicokinetic study is available on 3.3.5-trimethylcyclohexyl acrylate.

However, as per REACH guidance document R7.C , information on absorption, distribution, metabolism and excretion may be deduced from the physical-chemical properties and QSAR predictions.

Based on the physical-chemical properties and QSAR predictions, the absorption of 3.3.5-trimethylcyclohexyl acrylate is expected to be high by oral route and inhalation, but low by dermal route. A good distribution and excretion of the substance are expected.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

100

Additional information

No experimental toxicokinetic study is available on 3.3.5 -trimethylcyclohexyl acrylate.

However, as per REACH guidance document R7.C, information on absorption, distribution, metabolism and excretion may be deduced from the physical-chemical properties, including:

-Mean molecular weight: [142 -196] g/mol

-Water solubility: 18.3 mg/L (20°C)

-Partition coefficient Log Kow: [4,47 -4.6]

-Vapour pressure: 12.6 Pa (25°C)

 

ABSORPTION

The high value of log Kow (>4) and the low solubility (<100 mg/L) of 3.3.5 -trimethylcyclohexyl acrylate are favorable for a low oral absorption. Indeed, no clinical effects or mortality were observed after one single administration (2000 mg/kg) of 3.3.5-trimethylcyclohexyl acrylate by gavage (oral route) in rat. Using a model to predict either high or low fraction absorbed for an orally administered, passively transported substance, the rates of absorption of 3,3,5-trimethylcyclohexyl acrylate were 100 and 90% for a dose of 1 and 1000 mg, respectively (Danish QSAR). According to the model "Intestinal absorption (human)", 96.281% of the substance is absorbed (pkCSM).100% of oral absorption is taken into account for the risk assessment.

With a solubility of 18.3 mg/L, dermal absorption is anticipated to be low to moderate. A Log Kow higher close to 4 suggests that the rate of penetration of the substance may be limited by the rate of transfer between the stratum corneum and the epidermis. However, a molecular mass smaller than 500 g/mol are favourable to a dermal absorption. The acrylates are known to bind to skin components, and this binding decreases their dermal absorption. Indeed, the dermal absorption of 3.3.5-trimethylcyclohexyl acrylate is anticipated to be low. Indeed, no mortality was observed in the acute study by dermal route in rats. However, 3.3.5-trimethylcyclohexyl acrylate showed allergic reaction in the LLNA: it is evidence that some uptake must have occurred although it may only have been a small fraction of the applied dose. According to the IH skin perm (QSAR), the dermal absorption of 3,3,5-trimethylcyclohexyl acrylate is 0.8%.That's why 10% of absorption is taken into account for the risk assessment.

Based on the vapour pressure (12.6 Pa), 3.3.5 -trimethylcyclohexyl acrylate is considered to be not a volatile substance because lower than 100 Pa. Indeed, the absorption by inhalation can be expected to be low for 3.3.5-trimethylcyclohexyl acrylate based on the values of water solubility and log kow. However 100% of absorption is taken into account for the risk assessment (worst case).

DISTRIBUTION

No specific data is available on the distribution of 3.3.5-trimethylcyclohexyl acrylate.

No specific organ toxicity was observed in the 28 -day repeated toxicity study at the maximal dose of 1000 mg/kg/day.

According to the QSAR pkCSM, the substance is well distributed into the body including in the CNS.

METABOLISM

There are no experimental study on metabolism of 3.3.5 -trimethylcyclohexyl acrylate.

In silico tool (OECD QSAR Toolbox) was used to predict metabolites. OECD Toolbox contains simulators of liver metabolism and hydrolysis in acidic condition.

Acidic hydrolysis is expected and two metabolites are identified : 3,3,5-trimethylcyclohexanol and acrylic acid. These results are confirmed by the experimental hydrolysis performed according to the Test Guideline OECD 111.

The Rat liver S9 metabolism simulator showed 7 metabolites including 3,3,5-trimethylcyclohexanol and acrylic acid.

 

ELIMINATION

Due to the low water solubility, the excretion of 3.3.5 -trimethylcyclohexyl acrylate in the urines is expected to be low. An excretion via bile and faeces is possible.

According to the QSAR pkCSM, a high total clearance (hepatic & renal) is expected.