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Toxicological information

Dermal absorption

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Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2002
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: The documentation is from secondary literature.
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:
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:
weight of evidence
Study period:
2002
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: The documentation is from secondary literature.
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:
read-across source
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
Deviations:
no
Principles of method if other than guideline:
Comparison of human and pig (ear) dermatomed skin in vitro using Franz diffusion cells.
GLP compliance:
no
Remarks:
not specified
Radiolabelling:
yes
Remarks:
0.5 uCi of 14C labeled hexadecane
Species:
other: human and porcine skin
Strain:
not specified
Sex:
not specified
Type of coverage:
other: in vitro
Vehicle:
not specified
Duration of exposure:
24 hours with serial samples
Doses:
One mL of JP-8 fuel
Control animals:
no
Details on study design:
1 mL of JP-8 jet fuel containing 0.5 uCi of 14C- labeled hexadecane (1.92 x 10E-4 mM/mL JP-8) was applied to the skin the in donor side of the Franz diffusion cells. 6 cells/substance.
Details on in vitro test system (if applicable):
In Vitro Percutaneous Absorption. Franz diffusion cells were utilized. The surface of the epidermis exposed to the solution was 1 cm2. The pig/human skin was sandwiched between the cells with the dermal side towards receiver compartment. 1 mL of JP-8 jet fuel containing 0.5 uCi of 14C- labeled hexadecane was applied to the skin the in donor compartment (1.92 x 10E-4 mM/mL JP-8). Donor compartment was capped with a glass cap snugly fitted to prevent evaporation of the chemical. The receiver compartment contained 5 mL PBS and was constantly stirred. Aliquots of 20uL were withdrawn from the receiver compartment over the duration of the experiment. Six sets of experiments were performed for each chemical.

Determination to Powdered Pig/ Human Stratum Corneum. The binding of hexadecane was determined from powdered pig/human skin. The skin was pulverized with a mortar and pestle. The particles that passed through a 48-mesh sieve but retained by an 80-mesh sieve were used. The particles were mixed with 0.5 uCi of 14C- labeled hexadecane (1.92 x 10E-4 mM/mL JP-8) and allowed to come to equilibrium over 10h. The mixture was separated by centrifugation and the amount of bound chemical was determined by subtracting the recovered supernatant from total amount of chemical originally added through the use of a liquid scintillation counter.
Signs and symptoms of toxicity:
not examined
Dermal irritation:
not examined
Absorption in different matrices:
The flux, permeability coefficient (Kp), and binding of hexadecane for porcine skin was determined to be 8.80 +/- 0.00 (nmol/cm2/h) x 10E-3. The permeability coefficient (Kp), and binding of hexadecane for human skin were determined to be 7.02 +/- 0.00 (nmol/cm2/h) x 10E-3
Total recovery:
Not specified
Conversion factor human vs. animal skin:
Can be equivalent to 1.
Conclusions:
The flux, permeability coefficient (Kp), and binding of hexadecane for porcine skin was determined to be 8.80 +/- 0.00 (nmol/cm2/h) x 10E-3. The permeability coefficient (Kp), and binding of hexadecane for human skin were determined to be 7.02 +/- 0.00 (nmol/cm2/h) x 10E-3. Factor of difference (FOD) in the permeability of pig and human skin was 1.28 for hexadecane. The FOD in binding of hexadecane to pig and human skin was found to be 0.76.
Executive summary:

Human and pig skin pertmeability coefficient were compared using the determination of flux and permeability coefficient measured in a Franz cell. Measurements were made at 30 minutes, 1, 2, 4, 8, 12 and 24 hours. The flux, permeability coefficient (Kp), and binding of hexadecane for porcine skin was determined to be 8.80 +/- 0.00 (nmol/cm2/h) x 10E-3. The permeability coefficient (Kp), and binding of hexadecane for human skin were determined to be 7.02 +/- 0.00 (nmol/cm2/h) x 10E-3. Factor of difference (FOD) in the permeability of pig and human skin was 1.28 for hexadecane. The FOD in binding of hexadecane to pig and human skin was found to be 0.76.

Data source

Reference
Reference Type:
publication
Title:
In vitro permeability and binding of hydrocarbons in pig ear and human abdominal skin
Author:
Singh Somnath, Zhao Kaidi, Singh Jagdish
Year:
2002
Bibliographic source:
Drug and Chemical Toxicology 25( 1): 83-92

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
Deviations:
no
Principles of method if other than guideline:
Comparison of human and pig (ear) dermatomed skin in vitro using Franz diffusion cells.
GLP compliance:
no
Remarks:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
JP-8 fuel
Radiolabelling:
yes
Remarks:
0.5 uCi of 14C labeled hexadecane

Test animals

Species:
other: human and porcine skin
Strain:
not specified
Sex:
not specified

Administration / exposure

Type of coverage:
other: in vitro
Vehicle:
not specified
Duration of exposure:
24 hours with serial samples
Doses:
One mL of JP-8 fuel
Control animals:
no
Details on study design:
1 mL of JP-8 jet fuel containing 0.5 uCi of 14C- labeled hexadecane (1.92 x 10E-4 mM/mL JP-8) was applied to the skin the in donor side of the Franz diffusion cells. 6 cells/substance.
Details on in vitro test system (if applicable):
In Vitro Percutaneous Absorption. Franz diffusion cells were utilized. The surface of the epidermis exposed to the solution was 1 cm2. The pig/human skin was sandwiched between the cells with the dermal side towards receiver compartment. 1 mL of JP-8 jet fuel containing 0.5 uCi of 14C- labeled hexadecane was applied to the skin the in donor compartment (1.92 x 10E-4 mM/mL JP-8). Donor compartment was capped with a glass cap snugly fitted to prevent evaporation of the chemical. The receiver compartment contained 5 mL PBS and was constantly stirred. Aliquots of 20uL were withdrawn from the receiver compartment over the duration of the experiment. Six sets of experiments were performed for each chemical.

Determination to Powdered Pig/ Human Stratum Corneum. The binding of hexadecane was determined from powdered pig/human skin. The skin was pulverized with a mortar and pestle. The particles that passed through a 48-mesh sieve but retained by an 80-mesh sieve were used. The particles were mixed with 0.5 uCi of 14C- labeled hexadecane (1.92 x 10E-4 mM/mL JP-8) and allowed to come to equilibrium over 10h. The mixture was separated by centrifugation and the amount of bound chemical was determined by subtracting the recovered supernatant from total amount of chemical originally added through the use of a liquid scintillation counter.

Results and discussion

Signs and symptoms of toxicity:
not examined
Dermal irritation:
not examined
Absorption in different matrices:
The flux, permeability coefficient (Kp), and binding of hexadecane for porcine skin was determined to be 8.80 +/- 0.00 (nmol/cm2/h) x 10E-3. The permeability coefficient (Kp), and binding of hexadecane for human skin were determined to be 7.02 +/- 0.00 (nmol/cm2/h) x 10E-3
Total recovery:
Not specified
Conversion factor human vs. animal skin:
Can be equivalent to 1.

Applicant's summary and conclusion

Conclusions:
The flux, permeability coefficient (Kp), and binding of hexadecane for porcine skin was determined to be 8.80 +/- 0.00 (nmol/cm2/h) x 10E-3. The permeability coefficient (Kp), and binding of hexadecane for human skin were determined to be 7.02 +/- 0.00 (nmol/cm2/h) x 10E-3. Factor of difference (FOD) in the permeability of pig and human skin was 1.28 for hexadecane. The FOD in binding of hexadecane to pig and human skin was found to be 0.76.
Executive summary:

Human and pig skin pertmeability coefficient were compared using the determination of flux and permeability coefficient measured in a Franz cell. Measurements were made at 30 minutes, 1, 2, 4, 8, 12 and 24 hours. The flux, permeability coefficient (Kp), and binding of hexadecane for porcine skin was determined to be 8.80 +/- 0.00 (nmol/cm2/h) x 10E-3. The permeability coefficient (Kp), and binding of hexadecane for human skin were determined to be 7.02 +/- 0.00 (nmol/cm2/h) x 10E-3. Factor of difference (FOD) in the permeability of pig and human skin was 1.28 for hexadecane. The FOD in binding of hexadecane to pig and human skin was found to be 0.76.