Bis[(3,4-epoxycyclohexyl)methyl] adipate

Endpoint summary

Description of key information

Introduction

No experimental data on absorption, distribution, metabolism and excretion are available for bis((3,4-epoxycyclohexyl)methyl) adipate (CAS Number 3130-19-6; EC Number 221-518-5) also known as Uvicure S128. Very limited toxicity data are available for Uvicure S128; the majority of the data come from the structurally similar substance 7-oxabicyclo[4.1.0]hept-3-ylmethyl 7-oxabicyclo[4.1.0]heptane-3-carboxylate (CAS Number:2386-87-0;EC Number:219-207-4 – Source Substance). Toxicity data on the Source Substance in combination with the physicochemical data on Uvicure S128 were used to provide the toxicokinetic profile of Uvicure S128.

   

Physicochemical properties

The substanceUvicure S128is a clear viscous liquid with a molecular weight of 366.454 g/mol. The relative density of the test material was determined to be 1.1495 at 20°C. No melting point for the substance could be measuredin the temperature range from -100 to 250 °C. The vapour pressure ofUvicure S128 is 1.5 ×10^-5, 2.8 ×10^-5and 4.2 ×10^-4Pa, at 20, 25 and 50 °C, respectively. Therefore,Uvicure S128is considered to be very low volatile substance and not available for inhalation as a vapour.

The partition coefficient logPow is 2.98 at 20 °C and the water solubility is < 2.0 mg/L at 20 °C. ThereforeUvicure S128is a moderately lipophilic substance which is poorly soluble in water. The substance is readily biodegradable in water.

 

Oral absorption

The relatively low MW and moderate Log Pow would appear to favour oral absorption, however, the low water solubility may limit the rate absorption from the gastrointestinal tract. Results from the acute oral study with Uvicure S128 show that part of the dose was still present in the stomach at necropsy of the animals which died during the study. Nevertheless, rats showed signs of toxicity after administration. The repeat-dose data in rats with the Source Substance identified systemic effects in nasal epithelium, as well as in the kidney and liver (target organs), indicating systemic exposure. Oral absorption does take place, but the exact extent cannot be determined, therefore, for risk assessment purposes the oral absorption of Uvicure S128 is considered 50% in accordance with ECHA guidance.

Dermal absorption

Although the Log Pow value of 2.98 can be considered optimal for dermal penetration into the stratum corneum, the poor water solubility suggests a low to moderate dermal absorption. The substance is not irritating to the skin. Classification for skin sensitisation is triggered for Uvicure S128 (Target Substance) based on data with the Source Substance. In the absence of any quantitative data and in line with the EC guidance on dermal absorption (EFSA Panel on Plant Protection Products and their Residues (PPR); Guidance on Dermal Absorption. EFSA Journal 2012;10(4):2665), the default value of 25% for dermal absorption will be used for human health risk assessment purposes. 

Inhalation absorption

The low vapour pressure indicates that the substance cannot generate an inhalable vapour. Although the relatively low MW and moderate Log Pow would appear to favour absorption, the low water solubility suggest that most droplets, if inhaled, would not reach the alveolar region of the respiratory tract. However, in the absence of any quantitative data, and as a conservative approach, for human health risk assessment purposes absorption by inhalation is assumed to be 100%.

Distribution, Metabolism and Elimination

Repeat-dose oral toxicity studies with the Source Substance identified the liver, the kidney and the olfactory epithelium in the nasal tissues as the target organs. The relatively low molecular weight of the substance would suggest wider distribution although this might be countered by the low water solubility. There was however no evidence of bioaccumulation from the available repeat-dose toxicity studies.

Since positive results were obtained only in the presence of metabolic activation in in vitro genotoxicity tests with Uvicure S128 (Target Substance) and the Source Substance, it appears that Uvicure S128 is subjected to metabolism in the liver. The molecular weight would suggest prevalence of urinary excretion.

Conclusions

Oral, dermal and inhalation absorption of Uvicure S128 are considered to be 50%, 25% and 100%, respectively. 

There is no potential for bioaccumulation.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

25

Absorption rate - inhalation (%):

100