3,3,5-trimethylcyclohexyl methacrylate

Endpoint summary

Description of key information

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

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 methacrylate 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 methacrylate.

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: 210.32 g/mol

-Water solubility: 5.3 mg/L (20°C)

-Partition coefficient Log Kow: 5.25

-Vapour pressure: 7.3 Pa (25°C)

 

ABSORPTION

The high value of log Kow (>4) and the low solubility (<100 mg/L) of 3.3.5 -trimethylcyclohexyl methacrylate are favorable for a low oral absorption. No mortality or adverse effect were observed after one single administration (5000 mg/kg) of 3.3.5-trimethylcyclohexyl methacrylate by gavage (oral route) in rat.

However 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 methacrylate were 100 and 90% for a dose of 1 and 1000 mg, respectively (Danish QSAR). According to the model "Intestinal absorption (human)", 96.159% of the substance is absorbed (pkCSM). That's why 100% of oral absorption is taken into account for the risk assessment.

With a solubility of 5.3 mg/L, dermal absorption is anticipated to be low. A Log Kow higher than 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 methacrylates are known to bind to skin components, and this binding decreases their dermal absorption. According to the IH skin perm (QSAR), the dermal absorption of 3,3,5-trimethylcyclohexyl methacrylate is 0.55%.That's why 10% of absorption is taken into account for the risk assessment.

3.3.5-trimethylcyclohexyl methacrylate 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. That's why 10% of dermal absorption is taken into account for the risk assessment.

Based on the vapour pressure (7.3 Pa), 3.3.5 -trimethylcyclohexyl methacrylate 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 methacrylate based on the values of low water solubility and high 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 methacrylate.

No specific organ toxicity was showed in the repeated studies in the analogue substance : 3.3.5 -trimethylcyclohexyl acrylate.

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 methacrylate.

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 methacrylic acid.

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

 

ELIMINATION

Due to the low water solubility, the excretion of 3.3.5 -trimethylcyclohexyl methacrylate in the urines is expected to be low. An excretion via bile and faeces is possible. According to the QSAR pkCSM, a moderate/high total clearance (hepatic & renal) is expected.