Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
basic toxicokinetics, other
Type of information:
other: Assessment based on availbale 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

Constituent 1
Chemical structure
Reference substance name:
Diisodecyl adipate
EC Number:
248-299-9
EC Name:
Diisodecyl adipate
Cas Number:
27178-16-1
Molecular formula:
C26H50O4 (C24H46O4 - C28H54O4)
IUPAC Name:
bis(8-methylnonyl) adipate
Details on test material:
- Name of test material (as cited in study report): Diisodecyl adipate- Physical state: 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

Absorption

Oral:

The water solubility of diisodecyl adipate is very low («1 mg/L). After oral ingestion, this substance is expected to be hydrolysed in the gastro-intestinal fluids by the enzyme, carboxylesterase, producing the corresponding dicarboxylic acid (adipic acid) and alcohols (1-nonanol, 1-decanol and 1-undecanol). Adipic acid and the alcohols have molecular weights below 500; molecular weights below 500 are favourable for absorption from the gastrointestinal tract. Alcohols with long carbon chains and relatively low water solubility may be absorbed by micellar solubilisation. Therefore, for risk assessment purposes, the oral absorption is set at the default value 100%. The results of the toxicity studies do not provide reasons to deviate from this proposed oral absorption factor.

Inhalation:

Diisodecyl adipate has low volatility, i.e., very low vapour pressure (1.5 x 10-5Pa) and a high boiling point (385°C), and is therefore unlikely to be available for inhalation as a vapour. However, any diisodecyl adipate 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 diisodecyl adipate is set at 100%.

Dermal:

In view of its highly lipophilic character (log Po/w > 6),and the low water solubility («1 mg/L), the rate of transfer of diisodecyl adipate 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. According to ECHA guidance, a default value of 100% dermal absorption is generally used unless the molecular mass is above 500 and log P is outside the range [-1, 4]. The upper limit of the molecular mass range for this substance is 454.7 therefore the default 100% skin absorption figure should be applied.

Distribution

Products of the hydrolysis of diisodecyl adipate with high water solubility, such as adipic acid, are widely distributed in the body and do not have the potential to accumulate in adipose tissue due to their low log Pow. Based on the results of QSAR assessments, the substance is not predicted to be bicoaccumulative.

Metabolism and excretion

After oral ingestion, the substance is expected to be hydrolysed to adipic acid and alcohols in gastro-intestinal fluids by the enzyme, carboxylesterase, producing the corresponding acid and alcohols. After inhalation/dermal absorption, hydrolysis is likely to take place in the liver, catalysed by esterases. The hydrolysis products may be either excreted unchanged or absorbed and metabolised. Free alcohols can be transformed to fatty acids in a process catalysed by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Fatty acids are further degraded by β-oxidation. Adipic acid may be excreted unchanged or metabolised by β-oxidation. The metabolites are eliminated via renal and biliary excretion or are exhaled as carbon dioxide.

Applicant's summary and conclusion

Conclusions:
For risk assessment purposes the oral absorption is set at 100%
For risk assessment purposes the inhalation absorption is set at 100%
For risk assessment purposes the dermal absorption is set at 100%