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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

basic toxicokinetics in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labelling and/or risk assessment.

Data source

Reference Type:
Partition Coefficients of Low-Molecular-Weight Volatile Chemicals in Various Liquids and Tissues
Gargas ML, Burgess RJ, Voisard DE, Cason GH and Anderson ME
Bibliographic source:
Tocicol. Appl. Pharmacol., 98:87-99

Materials and methods

Objective of study:
other: determining partition coefficients
Principles of method if other than guideline:
Determination of the tissue to air and liquid to air partition coefficients of the test substance in human and rat blood and rat tissues.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
EC Number:
EC Name:
Cas Number:
Molecular formula:
Details on test material:
- Purity: > 98%

Test animals

other: CDF [F-344] CrlBr
Details on test animals or test system and environmental conditions:
- Source: Charles River Breeding Laboratory, Kinston, NY
- Weight at study initiation: between 200 and 300 g
- Housing: portable laminar air flow enclosure system
- Individual metabolism cages: no
- Diet: commercial food (Purina), ad libitum
- Water: tap water, ad libitum

- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
other: tissues were removed from animals then combined with the test item
Details on study design:
The liquids and tissues utilized were: 0.9% NaCl (saline) solution, reagent-grade olive oil heparanised rat, and human blood, and rat liver, muscle and fat tissues. Tissues were prepared as homogenates in saline solution in a 1:3 tissue weight:saline volume ratio (assuming a tissue density of 1.0 g/mL). The saline:air partition coefficient determinations were necessary to account for the amount of partitioning due to saline in the tissue homogenates and the oil:air values were used for comparison with the fat & coefficients. The saline:air and oil:air partition coefficients were also used as independent variables for modeling the blood and tissue:air values in multiple linear regression analyses.
Details on dosing and sampling:
Liquid scintillation vials with a septum were used incubate the sample matrix with the test item. The test item was introduced into the vials as a vapour by injecting 1 mL of atmosphere from a gas sampling bag containing an air concentration of between 5000 and 10000 ppm. The concentration of the test item in the vials was 200 to 400 ppm. After heating (37°C) and vortexing at 200 to 300 rpm for 15 minutes, equilibrium in the test vial was reached. The headspace chemical concentrations were sampled then analysed by gas chromatography utilizing a flame ionization detector.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Toxicokinetic parametersopen allclose all
Toxicokinetic parameters:
other: Human blood:air = 6.04±0.38
Toxicokinetic parameters:
other: Rat blood:air = 9.58±0.94
Toxicokinetic parameters:
other: Saline:air =1.41±0.04
Toxicokinetic parameters:
other: Olive oil:air = 178±6
Toxicokinetic parameters:
other: Rat fat:air = 148±11
Toxicokinetic parameters:
other: Rat liver:air = 8.96±0.61
Toxicokinetic parameters:
other: Rat muscle:air = 3.52±0.54

Metabolite characterisation studies

Metabolites identified:
not measured

Applicant's summary and conclusion

Interpretation of results (migrated information): other: partition coefficients were determined for rat blood/tissues and human blood
This study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).
The techniques presented in this study offer a method for determining liquid & and tissue:air partition coefficients for volatile chemicals such as the test item.
Executive summary:

A technique was developed to determine partition coefficients for low-molecular-weight, volatile compounds such as the test substance. The liquid:air and tissue:air partitions were determined in 0.9% saline, in olive oil, and in blood, liver, muscle, and fat tissues from rats. Human blood:air values were also determined. The test substance, as a vapour, was mixed with the matrix then incubated for 15 minutes to allow for equilibration. Samples of the headspace were analysed by gas chromatography and the partition coefficient determined. 


Values were:

Human blood:air = 6.04±0.38

Rat blood:air = 9.58±0.94

Saline:air =1.41±0.04

Olive oil:air = 178±6

Rat fat:air = 148±11

Rat liver:air = 8.96±0.61

Rat muscle:air = 3.52±0.54