Hexahydro-4,7-methano-1H-indenyl acrylate

Endpoint summary

Additional information

Assessment of the Toxicokinetic Behaviour

 

Dicyclopentadienyl acrylate (CAS-No.12542-30-2)

 

There were no studies available in which the toxicokinetic properties of dicyclopentadienyl acrylate were investigated.

 

Dicyclopentadienyl acrylate (molecular weight of 204.27 g/mol) is a clear, colourless and homogenous liquid with low water solubility(measured water solubility: 40 mg/L at 25 °C (BASF AG 1988, see chapter “water solubility”).The log Po/w was determined to be 4.3 at 23 °C (BASF SE 2010, see chapter “partition coefficient”), and a BCF= 60.18 L/kg indicating no bioaccumulation potential of dicyclopentadienyl acrylate is possible.The substance is described in the chapter “composition”, with acrylic acid (< 1%) and water (< 0.1%) as further components.

 

 

Absorption

In an acute oral toxicity study, rats were administered the substance by gavage at dose levels of 6810 and 10000 mg/kg bw. Mortality was reported in 1/10 animals at the lower dose and in 4/10 at the higher dose. At these high doses some nonspecific clinical signs of toxicity were observed; therefore bioavailability of the substance after oral administration is indicated (BASF AG 1980, see chapter “acute oral toxicity”).

 

In an acute dermal toxicity study in rats, the LD50 was determined to be 4840 mg/kg bw (Carpenter et al., 1974). Highly lipophilic substances (log P between 4 and 6) that come into contact with the skin can readily penetrate the lipid rich stratum corneum but are not well absorbed systemically. Although they may persist in the stratum corneum, they will eventually be cleared as the stratum corneum is sloughed off. Dermal uptake for such substances is expected to be low (ECHA GD 7c, 2008).

Taking into consideration the relatively high dermal LD50 and the physical-chemical properties of the substance, dermal uptake of the substance in humans is considered as limited.

 

Dicyclopentadienyl acrylate has a low vapour pressure of 0.0088 hPa at 20°C (BASF SE 2012, see chapter “vapour pressure”); accordingly, in an inhalation hazard test of the dissolved substance with saturated vapour atmosphere, none of the 12 tested rats showed clinical signs indicative for systemic availability after inhalative exposure.

 

 

Metabolism

Using the OECD toolbox vs.2.1, the liver metabolism simulator provided 25, and the skin simulator 6 potential metabolites (OECD toolbox vs.2.1, 2011). In general, the three simulators predicted the cleavage of the ester bond and the release of acrylic acid and the hydroxylated double-ring system.

 

The subsequent metabolism for acrylic acid involves metabolism to carbon dioxide via the propionate degradation pathway (acrylic acid --> 3-hydroxypropionic acid --> malonyl semialdehyde --> acetyl S CoA --> --> tricarboxylic acid cycle --> --> CO₂) (Black et al., 1995).

 

Potential epoxidation and further hydroxylation of metabolites was predicted for the double-ring system.

Studies on genotoxicity (Ames-Test, gene mutation in mammalian cells in-vitro, chromosome aberration assay in-vitro) gave no indications of a reactivity of the substance or its metabolites under the test conditions (i.e. no increased mutagenicity or cytotoxicity in treatments with metabolic activation).

These hydroxylated metabolites predicted by the OECD Toolbox are likely to be conjugated and excreted via urine.

 

 

Excretion

The potential metabolites as well as the parent chemical have a molecular weight lower than 500 g/mol. The potential metabolites are expected to be soluble in water and therefore are likely to be excreted predominantly via the urine (ECHA GD 7c, 2008).

 

 

 

Black et al. (1995). J. Toxicol. Environ. Health 45: 291-311

ECHA (2008). GD 7c. Endpoint specific Guidance.