[No public or meaningful name is available]

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study meets generally accepted scientific principles, acceptable for assessment.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study meets generally accepted scientific principles, acceptable for assessment.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across source

Signs and symptoms of toxicity:

not examined

Dermal irritation:

yes

The flux values for Normal-Heptane and the 10 and 60 min short-term absorption values (the quantity of chemical remaining in the skin plus that portion that had penetrated the skin was detected in the receptor fluid) were 63.2 µg/cm2/h, 113 µg/cm2/h (for the 10 min flux) and 22.1 µg/cm2/h (for the 60 min flux). Therefore, 10 min flux value for Normal-Heptane (based on both the amount in the skin and the receptor solution) was greater than the flux measured in a similar manner over 60 min.

Skin integrity measurements were taken before and after each experiment. All reporting laboratories (Normal-Heptane: Hask, DuPont Haskell Laboratory, USA) either used tritiated water permeability or electrical resistance (impedance) to confirm skin integrity; for consistency and to ease comparisons, all tritiated Kp values were converted to electrical impedance values expressed in kilo-ohms (k-ohms). A ratio of post- to pre-test impedance of "1" indicates that the skin barrier did not change over the course of the experiment. In the Kp experiments, skin exposed to Normal-Heptane had a damage ratio of 0.57, confirming that approx. 43% of the skin barrier function was lost due to exposure to Normal-Heptane. The barrier properties for the skin in the short-term experiments were given as the ratios of 0.90 for 10 min and 0.88 for 60 min.

Recovery of the applied dose, based on liquid scintillation count data when the radioactive chemical form was spiked into the non-radiolabeled chemical, was 95.5% (for the Kp experiment), 54.0% (for the 10 min experiment) and 110.0% (for the 60 min experiment).

At the end of the Kp experiment, the portion of Normal-Heptane in the skin (0.01%) was less than the portion in the receptor solution (0.12%). The portion of Normal-Heptane in the donor solution (wash) was 95.4%. In contrast to the Kp experiment, the skin (0.14%) retained a larger percentage of Normal-Heptane following a 10 min exposure. The portion of Normal-Heptane in the donor solution (wash) was 6.84% at 10 min. The greater portion of the applied dose remaining in the skin at 10 min suggests that partitioning into the skin from the donor solution is the driver of penetration with this brief exposure. After the 60 min experiments, there was also a larger percentage of n-heptane in the receptor solution (0.12%) than in the skin (0.06%). The increased proportion of Normal-Heptane detected in the receptor solution illustrates and confirms the movement of the chemical from the skin into the receptor solution.

Conclusions:

Under the test conditions, Normal-Heptane was able to penetrate the skin. During prolonged exposure, the penetration of the skin was aggravated, since the exposure to n-heptane simultaneously reduced skin barrier function.

Executive summary:

This data is being read across from the source study that tested heptane based on analogue read across.

Under the test conditions, Normal-Heptane was able to penetrate the skin. During prolonged exposure, the penetration of the skin was aggravated, since the exposure to Normal-Heptane simultaneously reduced skin barrier function.

Data source

Reference

Reference Type:

publication

Title:

In vitro dermal absorption rate testing of certain chemicals of interest to the occupational safety and health administration: Summary and evaluation of USEPA¿s mandated testing.

Author:

Fasano, W.J. and McDougal, J.N.

Year:

2008

Bibliographic source:

Regulatory Toxicology and Pharmacology 51: 181-194

Materials and methods

Principles of method if other than guideline:

Guidance for conduct of the in vitro dermal kinetic experiments was posted in the United States FR, April 26, 2004 (Volume 69, Number 80), pages 22402-22441, "In vitro dermal absorption rate testing of certain chemicals of interest to the occupational safety and health administration".

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Heptane

EC Number:

205-563-8

EC Name:

Heptane

Cas Number:

142-82-5

Molecular formula:

C7H16

IUPAC Name:

Heptane

Details on test material:

- Name of test material (as cited in study report): n-heptane
- Physical state: liquid
- Analytical purity: no data

Radiolabelling:

yes

Test animals

Species:

other: in vitro human skin model

Strain:

other: in vitro human skin model

Sex:

not specified

Details on test animals or test system and environmental conditions:

not applicable

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

up to 60 min

Doses:

infinite dose: 1200 µL/cm2
10 min: 20 µL
60 min: 20 µL

No. of animals per group:

in vitro human skin model

Control animals:

no

Details on in vitro test system (if applicable):

see "any other information on materials and methods"

Results and discussion

Signs and symptoms of toxicity:

not examined

Dermal irritation:

yes

Any other information on results incl. tables

The flux values for Normal-Heptane and the 10 and 60 min short-term absorption values (the quantity of chemical remaining in the skin plus that portion that had penetrated the skin was detected in the receptor fluid) were 63.2 µg/cm2/h, 113 µg/cm2/h (for the 10 min flux) and 22.1 µg/cm2/h (for the 60 min flux). Therefore, 10 min flux value for Normal-Heptane (based on both the amount in the skin and the receptor solution) was greater than the flux measured in a similar manner over 60 min.

Skin integrity measurements were taken before and after each experiment. All reporting laboratories (Normal-Heptane: Hask, DuPont Haskell Laboratory, USA) either used tritiated water permeability or electrical resistance (impedance) to confirm skin integrity; for consistency and to ease comparisons, all tritiated Kp values were converted to electrical impedance values expressed in kilo-ohms (k-ohms). A ratio of post- to pre-test impedance of "1" indicates that the skin barrier did not change over the course of the experiment. In the Kp experiments, skin exposed to Normal-Heptane had a damage ratio of 0.57, confirming that approx. 43% of the skin barrier function was lost due to exposure to Normal-Heptane. The barrier properties for the skin in the short-term experiments were given as the ratios of 0.90 for 10 min and 0.88 for 60 min.

Recovery of the applied dose, based on liquid scintillation count data when the radioactive chemical form was spiked into the non-radiolabeled chemical, was 95.5% (for the Kp experiment), 54.0% (for the 10 min experiment) and 110.0% (for the 60 min experiment).

At the end of the Kp experiment, the portion of Normal-Heptane in the skin (0.01%) was less than the portion in the receptor solution (0.12%). The portion of Normal-Heptane in the donor solution (wash) was 95.4%. In contrast to the Kp experiment, the skin (0.14%) retained a larger percentage of Normal-Heptane following a 10 min exposure. The portion of Normal-Heptane in the donor solution (wash) was 6.84% at 10 min. The greater portion of the applied dose remaining in the skin at 10 min suggests that partitioning into the skin from the donor solution is the driver of penetration with this brief exposure. After the 60 min experiments, there was also a larger percentage of n-heptane in the receptor solution (0.12%) than in the skin (0.06%). The increased proportion of Normal-Heptane detected in the receptor solution illustrates and confirms the movement of the chemical from the skin into the receptor solution.

Applicant's summary and conclusion

Conclusions:

Under the test conditions, Normal-Heptane was able to penetrate the skin. During prolonged exposure, the penetration of the skin was aggravated, since the exposure to n-heptane simultaneously reduced skin barrier function.

Executive summary:

Under the test conditions, Normal-Heptane was able to penetrate the skin. During prolonged exposure, the penetration of the skin was aggravated, since the exposure to Normal-Heptane simultaneously reduced skin barrier function.