Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: Assessment based on available information
Adequacy of study:
key study
Study period:
August 2010
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: non-GLP assessment report

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Objective of study:
other: toxicokinetic assessment
Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
Assessment of all available data
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2,2-bis[[(2-ethyl-1-oxohexyl)oxy]methyl]propane-1,3-diyl bis(2-ethylhexanoate) (BEBE)
- Physical state: Clear colourless oily liquid
- Analytical purity: >80%

Test animals

Species:
other: none
Strain:
other: none

Administration / exposure

Route of administration:
other: oral, dermal, inhalation
Vehicle:
unchanged (no vehicle)
Details on exposure:
see assessment

Results and discussion

Any other information on results incl. tables

The water solubility of BEBE is very low («1 mg/L). Since in general a compound needs to be dissolved before it can be taken up from the gastro-intestinal tract, it seems unlikely that BEBE will show a high systemic exposure after oral administration (1). However, its highly lipophilic character (log Po/w > 6) indicates that uptake by micellular solubilisation may be of particular importance. For risk assessment purposes oral absorption is set at 100%. The results of the toxicity studies do not provide reasons to deviate from this proposed oral absorption factor.

 

Once absorbed, distribution of BEBE throughout the body will be limited by low water solubility. Intracellularcentration of BEBE is expected to be higher than extracellular concentration, based on its lipophilic character. The concentration in breast milk may be higher than in blood/plasma. As a lipophilic substance, BEBE may concentrate in adipose tissue and depending on the conditions of exposure may accumulate. Daily exposure to BEBE may result in a build up in the body. Once exposure stops, the concentration in the body will decline at a rate determined by the half-life of the substance. BEBE may be conjugated and excreted via the bile and may also undergo enterohepatic recycling (circulation of bile from the liver, where it is produced, to the small intestine, where it aids in digestion of fats and other substances, back to the liver) which will prolong its biological half-life (2).

 

BEBE has low volatility, i.e., very low vapour pressure (3.06´10-7Pa) and a high boiling point (415°C), and is therefore unlikely to be available for inhalation as a vapour. However, any BEBE reaching the respiratory epithelium may be taken up by micellular solubilisation, because of its highly lipophilic character (log Po/w > 6) and low water solubility. For risk assessment purposes the inhalation absorption of BEBE is set at 100%.

 

In view of its highly lipophilic character (log Po/w > 6),and the low water solubility («1 mg/L), the rate of transfer of BEBE between the stratum corneum and the epidermis will be slow, and uptake into the stratum corneum itself may be slow. Any substance persisting in the stratum corneum may eventually be cleared as the stratum corneum is sloughed off. A dermal absorption of 10% is proposed for risk assessment purposes.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): low bioaccumulation potential based on study resultsFor riskassessment purposes the oral absorption is set at 100%For riskassessment purposes the inhalation absorption is set at 100%For riskassessment purposes the dermal absorption is set at 10%