4,4'-isopropylidenebis[2-allylphenol]

Endpoint summary

Description of key information

For oral and inhalation route, the default values from the REACH guidance (Chapter 8, R.8.4.2) are used fro DNEL derivation: 100% for inhalation, 50% for oral. Based on the log Kow of 4.12 and molecular weight of the substance, the skin permeability  according to Fitzpatrick et al (2004) of the substance is considered to be moderately permeable to the skin. Therefore, a ratio of 0.5 for oral to dermal absorption is provisonally suggested for DNEL derivation.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

25

Absorption rate - inhalation (%):

100

Additional information

Toxocokinetic bahaviour:

The test item is a straw coloured viscous liquid. The low vapour pressure value (5.4 x 10E-5 Pa at 25°C, Tremain, 2014) and predicted negative explosive and oxidising properties (Tremain, 2014) shows that the substance is of low volatility therfore inhalation is not a significant route of exposure. The test item was indicated to be a sensitizer (Henzell, 2014). The results from the repeated dose reproductive screening study in rats (Fulcher, 2014) produced nephrotoxicty at 250 mg/kg bw/day, lower pregnancy rates et 750/500 mg/kg bw/day there waw no effect on offspring survival, growth and development rated but to a dosage of 500 mg/kg bw/day.

Absorption:

The lipophilic nature of the substance (Log Pow 4.12, O'Connor, 2014) would suggest that the gastro-intestinal tract provides a route of absorption, following oral administration, before entering the circulatory system via the blood. Limited absoption may also take place via the skin as the test item was shown to be sensitizer (Henzell, 2014) and the test item could penetrate the dermal membrane through damaged skin.

Distribution:

There was evidence of systemic toxicity following the conduct of a repeated dose reproductive screening study in the rat (Fulcher, 2014). Furthermore the positive response in a sensitization study suggests that the test item nmay bind to carrier proteins in the circulatory systems (Henzell, 2014), thereby facilitating systemic distribution.

Metabolism:

The results of the reproductive/developmental toxicity screening study performed in male and female rats exposed to the test item at dosage up to 750 (reduced to 500) mg/kg bw/day elicited histopathological evidence of abnormal hepatic metabolism, a condition associated with enhanced metabolism, a condition associated with enhanced metbolism. A dditionally, nephrotoxicity was identified at 250 mg/kg bw/day.

Excretion:

There is no evidence to indicate the route of excretion but low water-soluble products are not favourable for urinary excretion and therefore biliary excretion may be the most plausible route of excretion of the test item via the faeces. Metabolism of the parent material may involve rendering it

more water soluble thereby enhancing renal excretion. The neprotoxicity identified in the reproductive/developmental toxicity screening study (Fulcher, 2014) may therefore have been a consequence of the renal route being a point of excretion.

Conclusion:

The available information suggests that absorption of the test substance would take place from the gastrointestinal tract. Some limited absorption may also be possible through the skin. Once absorbed, the substance would be distributed via circulatory system and the faeces is the most probable route of excretion