Registration Dossier

Toxicological information

Dermal absorption

Currently viewing:

Administrative data

dermal absorption in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-guideline study, GLP status not known, experimental animal study, published in peer reviewed literature, minor restrictions in design and/or reporting but otherwise adequate for assessment.

Data source

Reference Type:
Evaluation of the Dermal Bioavailability of Aqueous Xylene in F344 Rats and Human Volunteers .
Thrall KD and Woodstock AD
Bibliographic source:
Journal of Toxicology and Environmental Health Part A 66 (13):1267-1281

Materials and methods

Test guideline
no guideline followed
Principles of method if other than guideline:
Dermal exposure animal study conducted according to a published method.
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:
High-performance liquid chromatography (HPLC)-grade xylene, as the ortho isomer (98% purity), was obtained from Sigma-Aldrich (Milwaukee, WI).
Specific details on test material used for the study:
High-performance liquid chromatography (HPLC)-grade xylene, as the ortho isomer (98% purity), was obtained from Sigma-Aldrich (Milwaukee, WI).
not specified

Test animals

Fischer 344
Details on test animals or test system and environmental conditions:
The animals were housed in solid-bottom cages with hardwood chips and were acclimated for 5 days to the room that they were held in. The room had humidity and temperature control and a a 12-hour light/dark cycle.
Certified Purina rodent chow (Ralston Purina Co., St. Louis, MO) and water were provided ad libitum throughout the acclimation period.

Animals had the hair on the lower back lightly clipper shaved while under restraint.

Administration / exposure

Type of coverage:
Dermal exposure patch that was sealed with silicon after addition of test material
unchanged (no vehicle)
Duration of exposure:
The animals were exposed dermally for 4 hours.
2 ml aqueous o-xylene was added to the exposure patch via a gas-tight syringe through a needle hole, which was then sealed using silicon.
The surface area of the skin exposed was 2.27 cm2.
The target concentration was 200 μg/ml (0.02%). The actual dosing volume was determined via weighing the syringe before and after dosing. To quantify total absorbed dose a weighted aliquot (100 μL) was collected from both the original dosing solution and the remaining solution at the end of the exposure, and both were analysed via gas chromatography.
No. of animals per group:
Not described. Dermal exposures were conducted as according to Thrall and Woodstock 2002.
Details on study design:
Rats were exposed to o-xylene dermally and its absorption were measured indirectly using real-time exhaled breath analysis, carried out in individual 2.2-L glass off-gassing chambers. The animals were placed in the chambers directly after dermal application, were awake and free to move and were supplied with "grade D" breathing air through the lid of the chamber at a calibrate date of approximately 12 L/h. Air samples were continually taken via the ASGDI-MS/MS system via a port in the lid at the same rate of 12 L/H and provided new data points every 1.6 s.

A PBPK model was used to calculate dermal permeability coefficient (K(p)).

The animals were sacrificed via CO2 asphyxiation at the end of the monitoring period and returned to the off-gassing chamber for several minutes to ensure that the xylene samples collected were via exhaled breath and not due to a leakage from the exposure patch system.

Results and discussion

Signs and symptoms of toxicity:
not specified
Dermal irritation:
not specified
Absorption in different matrices:
The estimated rat skin permeability coefficient to aqueous o-xylene is 0.058+/-0.009 cm/h (range: 0.05 - 0.07 cm/h, n = 6).
Percutaneous absorption
Key result
other: K(p)
0.058 other: dimensionless

Any other information on results incl. tables

Exhaled breath data shows an initial absorption phase with steady state exhaled breath concentration 1 hour after dermal dose application and a peak exhaled breath concentration of approximately 30 ppb. Variability in data likely reflects temporary variations in breathing rates and any movement by the animal.

Applicant's summary and conclusion

The estimated rat skin permeability coefficient to aqueous o-xylene is 0.058+/-0.009 cm/h (range: 0.05 - 0.07 cm/h, n = 6).
Executive summary:

Male F344 rats were dermally exposed to aqueous o-xylene. O-xylene absorption was measured using real-time exhaled breath analysis together with physiologically based pharmacokinetic (PBPK) modelling. The calculated rat skin permeability coefficient K(p) was 0.058 +/- 0.009 cm/h.