Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics, other
Type of information:
other: assessment of all available data
Adequacy of study:
key study
Study period:
December 2016
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: non-GLP assessment report

Data source

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
no guideline required

Results and discussion

Any other information on results incl. tables

The octanol/water partition coefficient of the different constituents of 2,2'-Isopropylidenebis(p-phenyleneoxy)diethanol were comprised between 2.5 and 4. The log Kow of the main constituent was 2.86. The molecular weight of 316 g.mol-1are favourable for absorption. The water solubility of 2,2'-Isopropylidenebis(p-phenyleneoxy)diethanol is moderate (111.8 mg/L). In general, a compound needs to be dissolved before it can be taken up from the gastro-intestinal tract after oral administration. Potential for ionization may result in impaired uptake since compounds need to pass the lipid membranes in the gastrointestinal wall. For risk assessment purposes the oral absorption of 2,2'-Isopropylidenebis(p-phenyleneoxy)diethanol is set at 50% as a worst case assumption. The results of the toxicity studies do not provide reasons to deviate from this proposed oral absorption factor.

Absorbed 2,2'-Isopropylidenebis(p-phenyleneoxy)diethanol might undergo biotransformation. Because of the moderate molecular weight, the conjugates will either be excreted via the bile or the urine.

As 2,2'-Isopropylidenebis(p-phenyleneoxy)diethanol is considered as a clear yellowish waxy solid with white lump i.e. (sort of suspension, liquid), no particle size was determined. In addition, the vapour pressure of the test substance at 20°C was very low (3.1x10-7 Pa). However, for risk assessment purposes the inhalation absorption of 2,2'-Isopropylidenebis(p-phenyleneoxy)diethanol is set at 100% as a worst case assumption.

 

2,2'-Isopropylidenebis(p-phenyleneoxy)diethanol being a waxy solid with a moderate water solubility (111.8 mg/L) has the potential for dermal absorption. Its molecular weight (316) and log Pow (2.5 to 4) are indicative to be moderately favorable for dermal uptake. However, the criteria for 10% dermal absorption as given in the Reach Guidance on information requirements and chemical safety assessment (MW>500 and -1<log Pow >4) are not met, and therefore 100% dermal absorption of 2,2'-Isopropylidenebis(p-phenyleneoxy)diethanol should be considered for risk assessment purposes. It is, however, generally accepted that dermal absorption is not higher compared to oral absorption. The 100% dermal absorption derived from physical/chemical properties of the substance should therefore be considered as a non-realistic assumption, and for risk assessment purposes a lower dermal absorption of 50% might be considered more appropriate.

 

Based on the present available data, no additional conclusions can be drawn on the distribution, metabolism and excretion of 2,2'-Isopropylidenebis(p-phenyleneoxy)diethanol after dermal or oral absorption or inhalation.

Applicant's summary and conclusion

Conclusions:
The evaluation of currently available information on 2,2'-Isopropylidenebis(p-phenyleneoxy)diethanol led to the following toxicokinetic assessment:
For risk assessment purposes, the oral absorption is set at 50%.
For risk assessment purposes the inhalation absorption is set at 100%.
For risk assessment purposes the dermal absorption is set at 50%.