Distillates (Fischer-Tropsch), 210-360 degree Celcius, hydrotreated, isoalkanes, cyclics, <0.1% aromatics

Dermal absorption

Administrative data

Endpoint:

dermal absorption

Type of information:

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

Adequacy of study:

key study

Study period:

2003

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable well-documented study report which meets basic scientific principles: non-GLP. Source of data is from secondary literature.

Data source

Reference

Reference Type:

publication

Title:

Percutaneous absorption, biophysical, and macroscopic barrier properties of porcine skin exposed to major components of JP-8 jet fuel

Author:

Singh, Somnath; Singh, Jagdish

Year:

2003

Bibliographic source:

Environmental Toxicology and Pharmacology (2003), 14(1-2), 77-85. ISSN: 1382-6689

Materials and methods

Principles of method if other than guideline:

Three aliphatic (dodecane, tridecane, and tetradecane) chemicals, major components of JP-8, were investigated for changes in skin lipid and protein biophysics, and macroscopic barrier perturbation from dermal exposure. Percutaneous absorption was examined in vitro using porcine ears (Yorkshire marine pigs, male). Fourier transform infrared (FTIR) spectroscopy was employed to investigate the biophysical changes in stratum corneum (SC) lipid and protein. FTIR results showed that all of the above five components of JP-8 significantly (P< 0.05) extracted SC lipid and protein. Macroscopic barrier perturbation was determined by measuring the rate of transepidermal water loss (TEWL).

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Dodecane

EC Number:

203-967-9

EC Name:

Dodecane

Cas Number:

112-40-3

IUPAC Name:

dodecane

Constituent 2

Reference substance name:

Tridecane

EC Number:

211-093-4

EC Name:

Tridecane

Cas Number:

629-50-5

IUPAC Name:

tridecane

Constituent 3

Reference substance name:

Tetradecane

EC Number:

211-096-0

EC Name:

Tetradecane

Cas Number:

629-59-4

IUPAC Name:

tetradecane

Details on test material:

Dodecane (DOD)-1-14C (specific activity 8.3 mCi/mmol); tridecane (TRI)-1-14C (specific activity 53.5 mCi/ mmol); tetradecane (TET) -1-14C (specific activity 18.1 mCi/mmol)

Radiolabelling:

yes

Test animals

Species:

pig

Strain:

other: in vitro: from Yorkshire marine pigs

Sex:

male

Administration / exposure

Type of coverage:

other: in vitro

Details on study design:

Model System
Porcine ears (Yorkshire marine pigs, male) were obtained. The external/dorsal skin was dermatomed to 0.5 mm thickness and used in the in vitro percutaneous absorption and TEWL studies. The method of Kligman and Christophers was used to separate epidermis from whole skin to produce the stratum corneum (SC).

In vitro percutaneous absorption
Franz diffusion cells were used in the in vitro percutaneous absorption studies. The dermatomed skin was sandwiched between the cells with the epidermis facing the donor compartment. The maximum capacities of the donor and receiver compartments were 1 and 5 ml, respectively, and the effective diffusion area was 0.785 cm2. The donor compartment contained 4 mCi of radiolabeled test chemicals in 1 ml of JP-8 and the receiver compartment was filled with 5 ml of PBS, pH 7.4 containing 0.1% formaldehyde and 0.2% Tween 80 to act as preservative and solubilizer, respectively. The donor compartment was fitted to minimize evaporation of volatile test chemical. The cells were maintained at 37oC. At appropriate times, 1 ml samples were withdrawn from the receiver compartment and transferred to scintillation vials. The samples were assayed by liquid scintillation counting. The instrument was programmed to give counts for 10 min. Net dpm was obtained by subtracting background dpm measured in the control samples. All experiments were performed in replicates of six, and the results were expressed as the mean +/-S.D. (n = 6).

Binding of chemicals
SC was pulverized in a mortar with a pestle. Ten milligrams of pulverized SC was mixed by vortexing for 5 min with 1 ml of JP-8 containing 4 mCi of the test chemical. The mixture was shaken for 10 h at 37 8C. Since the lag time of these chemicals for attaining steady state transport was well below 2 h, 10 h contact time was considered adequate for reaching equilibrium. After 10 h of contact time, the mixture was separated by centrifugation, and the supernatant was removed. The sediment was resuspended three times in JP-8 to remove chemical adsorbed on the surface. The amount of radioactivity in the supernatants was determined by liquid scintillation counting. The amount of chemical that bound to the SC was obtained by subtracting the amount of chemical recovered in supernatants from the amount of chemical originally added. Six sets of experiments were performed for each chemical.

Biophysical properties of SC lipids and proteins by FTIR
The SC samples were treated for 24 h by applying 500ml of chemical on 10 cm2 area of SC in a closed petridishes. The samples were vacuum-dried (650 mmHg) at 21oC for 3 days and stored in a desiccator to evaporate JP-8 (Yamane et al., 1995). The treated SC was then subjected to FTIR spectroscopy. Attention was focused on characterizing the occurrence of peaks near 2850 and 2920 per cm, which were due to the symmetric and asymmetric C-H stretching, respectively. Strong amide absorbance occurred in the region of 1500-1700 per cm due to C-O stretching and N-H bending. The decrease in peak heights and areas of methylene and amide absorbances is related to the SC lipid and protein extraction, respectively. For each SC sample, peak height and area were measured before and after the chemical treatment. This experimental strategy allowed each sample to serve as its own control.

In vitro transepidermal water loss (TEWL) through skin
Franz diffusion cells were used for in vitro TEWL studies. The dermatomed skin was treated with chemical in a manner similar to the SC for FTIR studies. The treated dermatomed skin was then sandwiched between the diffusion cells with the SC side up and the dermal side exposed to the receiver compartment containing isotonic saline (0.9% sodium chloride solution). Holding the probe over the donor cell opening until a stable TEWL value was achieved performed TEWL measurement. The experiments were performed in a room with an ambient temperature between 20 and 26 oC and relative humidity between 30 and 45%. In all the cases, six replicates of experiments were performed and the results expressed as the mean +/- S.D. (n=6). Experiments were performed in the same manner without chemical treatment of the dermatomed skin to serve as control.

Data analysis
The chemical concentration was corrected for sampling effects (Hayton and Chen, 1982): The permeability coefficient (Kp) was calculated as (Scheuplein, 1978): The binding of chemicals to the SC (P) was calculated as (Zhao and Singh, 2000). Statistical comparisons were made using the Student’s t -test and analysis of variance (ANOVA). The level of significance was taken as P< 0.05.

Results and discussion

Signs and symptoms of toxicity:

not examined

Dermal irritation:

not examined

Any other information on results incl. tables

RESULTS

Binding to the stratum corneum can be determined by calculating the Log PC (octanol/water) values. There is an increase in binding of the aliphatic JP-8 components to with increasing Log PC value. Log PC values are 8.76 +/- 0.74, 13.15 +/- 1.05, 15.85 +/- 1.36 for dodecane (DOD), tridecane (TRI), and tetradecane (TET), respectively.

The flux (JSS), values were determined to be (mean) 1.94, 13.80, and 1.40 (nmol/cm2 per h)*10E-2 for DOD, TRI, and TET, respectively. The diffusion coefficient values were determined to be (0.21 +/- 0.02)E-6, (6.84 +/- 0.57)E-6,  and (0.20 +/- 0.04)E-6 cm2/h for DOD, TRI, TET, respectively. The lag time, values were determined to be (mean) 1.33, 0.89, and 1.63 hours for DOD, TRI, and TET, respectively. FTIR results suggest that all of the test chemicals significantly (P<0.05) extracted SC lipid and protein in comparison to control. TRI exhibited greater extraction of the SC lipid and protein as well as greater transport through the skin than other chemicals.

 

The TEWL values through control and chemically treated porcine skin. All of the test chemicals caused significant (P/0.05) increase in TEWL in comparison to control. TRI produced larger increase in TEWL (29.22 +/- 0.99 g/m2 per h) followed by DOD (15.15 +/- 1.34 g/m2 per h), and TET (11.64 +/- 1.42 g/m2 per h).

Applicant's summary and conclusion

Conclusions:

Retention in the stratum corneum can be determined by calculating the Log PC (octanol/water) values. There is an increase in the retention of the aliphatic JP-8 components to with increasing Log PC value. Log PC values are 8.76 +/- 0.74, 13.15 +/- 1.05, 15.85 +/- 1.36 for dodecane (DOD), tridecane (TRI), and tetradecane (TET), respectively.

The flux, JSS (nmol/cm2 per h)*10E-2, values were determined to be 1.94 +/- 0.39, 13.80 +/- 0.82, and 1.40 +/- 0.20 for DOD, TRI, and TET, respectively. The permeability coefficients, Kp (cm/h)*10E-4, were 0.37 +/- 0.13, 18.46 +/- 1.50, 0.64 +/- 0.20 for DOD, TRI, and TET, respectively. The diffusion coefficient values, D (cm/h)*10E-6, were determined to be 0.21 +/- 0.02, 6.84 +/- 0.57, and 0.20 +/- 0.04 for DOD, TRI, TET, respectively. The lag time (hours) was determined to be 1.33 +/- 0.07, 0.89 +/- 0.17, and 1.62 +/- 0.34 hours for DOD, TRI, and TET, respectively. FTIR results suggest that all of the test chemicals significantly (P<0.05) extracted SC lipid and protein in comparison to control. TRI exhibited greater extraction of the SC lipid and protein as well as greater transport through the skin than other chemicals.

Executive summary:

Three aliphatic (dodecane, tridecane, and tetradecane) chemicals, major components of JP-8, were investigated for changes in skin lipid and protein biophysics, and macroscopic barrier perturbation from dermal exposure. Percutaneous absorption was examined in vitro using porcine ears (marine pigs, male).  Fourier transform infrared (FTIR) spectroscopy was employed to investigate the biophysical changes in stratum corneum (SC) lipid and protein. FTIR results showed that all of the tested components of JP-8 significantly (P < 0.05) extracted SC lipid and protein.

Retention in the stratum corneum can be determined by calculating the Log PC (octanol/water) values. There is an increase in the retention of the aliphatic JP-8 components to with increasing Log PC value. Log PC values are 8.76 +/- 0.74, 13.15 +/- 1.05, 15.85 +/- 1.36 for dodecane (DOD), tridecane (TRI), and tetradecane (TET), respectively.

 

The flux, JSS (nmol/cm2 per h)*10E-2, values were determined to be 1.94 +/- 0.39, 13.80 +/- 0.82, and 1.40 +/- 0.20 for DOD, TRI, and TET, respectively. The permeability coefficients, Kp (cm/h)*10E-4, were 0.37 +/- 0.13, 18.46 +/- 1.50, 0.64 +/- 0.20 for DOD, TRI, and TET, respectively. The diffusion coefficient values, D (cm/h)*10E-6, were determined to be 0.21 +/- 0.02, 6.84 +/- 0.57, and 0.20 +/- 0.04 for DOD, TRI, TET, respectively. The lag time (hours) was determined to be 1.33 +/- 0.07, 0.89 +/- 0.17, and 1.62 +/- 0.34 hours for DOD, TRI, and TET, respectively. FTIR results suggest that all of the test chemicals significantly (P<0.05) extracted SC lipid and protein in comparison to control. TRI exhibited greater extraction of the SC lipid and protein as well as greater transport through the skin than other chemicals.