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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994

Materials and methods

Objective of study:
absorption
Test guideline
Qualifier:
no guideline available
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: low viscosity liquid hydrocarbon
Details on test material:
Blend of straight run hydrotreated kerosine (30%) and hydrocracked kerosine (70%)
Composition %: Saturates 76.3, Aromatics 21.8 and Olefins 1.9
Radiolabelling:
yes
Remarks:
14C-labelled naphthalene or 14C-labelled n-tetradecane

Test animals

Species:
mouse
Strain:
C3H
Sex:
male

Administration / exposure

Route of administration:
dermal
Vehicle:
other: mineral oil
Duration and frequency of treatment / exposure:
96 hour(s)
Doses / concentrations
Remarks:
Doses / Concentrations:
Males: 15 µl undiluted and 60 µl diluted to 25% with mineral oil
No. of animals per sex per dose:
Males: 5

Results and discussion

Toxicokinetic / pharmacokinetic studies

Toxicokinetic parametersopen allclose all
Toxicokinetic parameters:
half-life 1st:
Toxicokinetic parameters:
half-life 2nd:
Toxicokinetic parameters:
half-life 3rd:

Any other information on results incl. tables

In the study with dermally applied undiluted test material approximately 5% of the labelled tetradecane and 15% of the labelled naphthalene was absorbed over 96 hours. In the study with the 25% concentration of test material, approximately 7% of the labelled tetradecane and 16% of the labelled naphthalene was absorbed over 96 hours.

In the passive inhalation study approximately 2.8% (undiluted test
 material) and 1.8% (25% concentration) of the labelled naphthalene was absorbed.  In contrast, approximately 0.2% of labelled tetradecane in undiluted and diluted test material was absorbed.

These studies demonstrate that dilution of the test material in mineral
 oil did not influence absorption of the radiolabelled "spikes" present.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): low bioaccumulation potential based on study results constituents of kerosine are absorbed through the skin
Comparison of data from testing with undiluted material and data, obtained with a 25% concentration of the test compounds diluted in mineral oil, revealed that the difference in absorption of the radiolabelled "spikes" was insignificant, therefore it can be concluded that dilution did not affect the absorption of the test compound. The difference in absorption of 14C-labelled naphthalene or 14C-labelled n-tetradecane, showed that aromatics are absorbed better than saturates.
Executive summary:

The test material (blend of straight run hydrotreated kerosine (30%) and hydrocracked kerosine (70%)) was fortified before dosing with either 14C-labelled naphthalene or 14C-labelled n-tetradecane as surrogates representing the aromatic and saturates fraction. Either 15 µl of undiluted test material or 60 µl of test material diluted to 25% in mineral oil was applied as a single dose into a rubber chamber that had been previously affixed to the skin with epoxy and cyanoacrylate. A metal covering was placed on top of the chamber to prevent loss of test material. The animals were placed in metabolism chambers and urine and faeces were collected 24, 48, 72 and 96 hours after dosing. After 96 hours the animals were sacrificed and any unabsorbed test material was removed from the test site. The dosed area of skin was then removed from the carcass and processed for analysis of radiotracers. Samples of urine and faeces were also analysed for the presence of radiotracers. Percutaneous absorption was determined by summing the 14C activity in the urine, faeces and expired air and tissues.
Further groups of 5 males were used to assess the passive inhalation of
 labelled test material. This was accomplished by placing animals in metabolism chambers and collecting urine and faeces in a similar manner to that used for the dermally exposed animals. The labelled test material at the same doses as for the dermal study was placed in scintillation vials that were fixed to the inner wall of the metabolism chamber in a way that the animals could not come into contact with the vials.

In the study with dermally applied undiluted test material approximately 5% of the labelled tetradecane and 15% of the labelled naphthalene was absorbed over 96 hours. In the study with the 25% concentration of test material, approximately 7% of the labelled tetradecane and 16% of the labelled naphthalene was absorbed over 96 hours. In the passive inhalation study approximately 2.8% (undiluted test material) and 1.8% (25% concentration) of the labelled naphthalene was bioavailable. In contrast, approximately 0.2% of labelled tetradecane in undiluted and diluted test material was absorbed.
These studies demonstrate that dilution of the test material in mineral
 oil did not influence absorption of the radiolabelled "spikes" present and that aromatics are absorbed better than saturates.