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Endpoint:
basic toxicokinetics
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1988
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: supporting information
Qualifier:
no guideline followed
Principles of method if other than guideline:
Mass Balance
Executive summary:

The fate of pristane (2, 6, 10, 14-tetramethylpentadecane) was studied in rats after a single per os administration of 3H-labeled pristane. The balance study showed extensive fecal excretion (66%) mainly as unchanged hydrocarbon, whereas about 14% of ingested pristane was excreted in urine as pristane metabolites and tritiated water. After one week, 8.3% of the ingested 3H still was stored in the carcass and the radioactive distribution in tissues and organs showed a preferential incorporation into adipose tissue and liver. Over 75% of the radioactivity stored in the carcass was associated with pristane metabolites and tritiated water. Tissue metabolites were characterized by thin layer chromatography, gas chromatography, and mass spectrometric analyses. Four metabolites were identified: pristan-1-ol, pristane-2-ol, pristanic acid and 4, 8, 12-trimethyltridecanoic acid. These results demonstrated that pristane undergoes subterminal hydroxylation or terminal oxidation followed by the classical beta-oxidation process. Incorporation of metabolites in phospholipids and more particularly in the phosphatidylserine fraction has been observed.

Endpoint:
basic toxicokinetics
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable well-documented study report which meets basic scientific principles.
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: supporting information
Principles of method if other than guideline:
Labeled paraffins with 8-18 C atoms prepared from unsaturated hydrocarbons by addition of deuterium have been added in oily solution to normal rats’ food.
Conclusions:
Interpretation of results:
After six days an increase of deuterium content in the body fluid of all the rats was observed indicating that the labeled compounds had been metabolized.
Executive summary:

Labeled paraffins with 8-18 C atoms prepared from unsaturated hydrocarbons by addition of deuterium have been added in oily solution to normal rats’ food. After six days an increase of deuterium content in the body fluid of all the rats was observed indicating that the labeled compounds had been metabolized. Deuterium was found in the fatty acids of the body fats and the liver lipids especially after feeding octadecane and hexadecane. Isolating oleic, stearic, and palmitic acids containing deuterium, indicated that methyl- and beta-oxidation of these hydrocarbons has occurred. Fatty acids resulting from the metabolism of hydrocarbons with shorter chains were not deposited but in these cases the urine contained fatty acids with higher deutrium content than after administration of octadecane and hexadecane. According to the deuterium content of the neutral fractions from the liver and body lipids all the hydrocarbons tested were deposited only to a small extent, the largest depots occurring mainly after feeding with octadecane and hexadecane.

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1999
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable well-documented study report which meets basic scientific principles.
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: supporting information
Principles of method if other than guideline:
In vitro isolated perfused porcine skin flap (IPPSF) Studies.
GLP compliance:
not specified
Radiolabelling:
yes
Remarks:
14C-naphthalene, 3H-dodecane, 14C- hexadecane
Species:
pig
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
in vitro experiment
Type of coverage:
open
Vehicle:
unchanged (no vehicle)
Duration of exposure:
5 hours; 4 trials
Doses:
25 uL of Jet fuel with radio labeled tracers
Control animals:
no
Details on study design:
In vitro isolated perfused porcine skin flap (IPPSF) Studies.
In these studies, jet fuel mixtures were applied non-occluded to mimic field exposure conditions, and experiments were conducted for a total of 5 h in IPPSFs with 4 replicates per treatment condition. A 1 x 5 cm dosing area was drawn on the surface of the skin flap with a surgery marker. A dose, containing 25 uL of the specified jet fuel containing approximately 2 uCi of 14C-naphthalene plus 10 uCi of 3H-dodecane and 14C- hexadecane was applied directly to the surface of the skin flap. The specific activities of the marker compounds were sufficient that the added radio labeled compounds had little effect on the final concentration of naphthalene (1.21% instead of 1.1%) and dodecane (4.701% instead of 4.7%).

Perfusate samples (3 ml) were collected every 5 min for the first 40 min then every 10 mm until 1.5 h. and then every 15 min until termination at 5 h. At termination, several samples were taken for mass balance of the marker compounds. The surface of the dose area was swabbed twice with a 1% soap solution and gauze, and then 12 stratum corneum tape strips were collected using cellophane tape (3M Corporation, Minneapolis. MN). The entire dose area was removed. A 1x 1 cm core of the dose area was removed and frozen for subsequent depth of penetration studies. This consisted of laying the core sample epidermal side down in an aluminum foil boat and embedding in Tissue-Tek OCT compound (Miles. Inc., Elkhart, IN), snap freezing in liquid nitrogen, followed by sectioning (40 zm) on a Reichart-Jung Model 1800 Cryocut (Warner Lambert, Buffalo, NY). The remaining dosed area as well as the surrounding skin was separated from the fat and held for analysis. All samples (including swabs, tape strips, core sections, skin, fat, mass balance samples, etc.) were dissolved separately in Soluene. A representative volume of each sample was oxidized completely via a Packard Model 307 Tissue Oxidizer. The 3H and 14C samples were counted separately on a Packard Model 1900TR TriCarb Scintillation Counter.

Data analysis. Data was entered into a custom IPPSF database and the resulting analysis reported. Since all experiments were conducted using the identical marker doses across all fuels, and the absolute concentrations of these marker compounds were similar, these results are expressed as percentage applied dose to give a representative assessment of the absorption and cutaneous penetration of a complex mixture such as jet fuel. This is appropriate since the absolute concentrations of jet fuel hydrocarbons are not fixed across all fuels due to differences that arise from the natural source of the petroleum and different refining processes. Area under the curve (AUC) in the perfusate was calculated using the trapezoidal method. Peak flux was the maximum flux (% dose/mm) observed at any one time point.

The experimental compartments which were analyzed in these studies used the following definitions: (1) Surface is the residue removed by washing the surface of the IPPSF at termination of the experiment plus the residues remaining in the dosing template. (2) Stratum corneum is the residue extracted from the outermost stratum corneum via 12 tape strips at the termination of the experiment. (3) Dosed skin is the residue that remained in the dosed skin plus the depth of penetration core taken at termination. (4) Absorption is the cumulative amount of the marker compound collected in the effluent over the course of the 5-h experiment. (5) Fat is the residue remaining in the fat when it was separated from the dermis at the end of the experiment. (6) Penetration is the summation of the label in the effluent plus skin plus fat, but not stratum corneum or surface. (7) Evaporative loss is that label which was lost to evaporation. Previous studies using IPPSF’s indicated that the penetration estimate is the best empirical correlate to predict eventual in vivo absorption in humans.

Statistical significance of absorption and penetration parameters were determined using ANOVA or by a priori-defined orthogonal contrasts where appropriate at the 0.05 level of significance. A least significance difference (LSD) procedure was used for multiple comparisons on overall tissue disposition.
Details on in vitro test system (if applicable):
A 1 x 5 cm dosing area was drawn on the surface of the skin flap with a surgery marker. A dose, containing 25 uLof the specified jet fuel containing approximately 2 uCi of 14C-naphthalene plus 10 uCi of 3H-dodecane and 14C- hexadecane was applied directly to the surface of the skin flap. Perfusate samples (3 ml) were collected every 5 min for the first 40 min then every 10 min until 1.5 hours and then every 15 min until termination at 5 hours. At termination, several samples were taken for mass balance of the marker compounds. The surface of the dose area was swabbed twice with a 1% soap solution and gauze, and then 12 stratum corneum tape strips were collected using cellophane tape (3M Corporation, Minneapolis. MN). The entire dose area was removed. A 1x 1 cm core of the dose area was removed and frozen for subsequent depth of penetration studies. This consisted of laying the core sample epidermal side down in an aluminum foil boat and embedding in Tissue-Tek OCT compound (Miles. Inc., Elkhart, IN), snap freezing in liquid nitrogen, followed by sectioning (40 zm) on a Reichart-Jung Model 1800 Cryocut (Warner Lambert, Buffalo, NY). The remaining dosed area as well as the surrounding skin was separated from the fat and held for analysis.
Signs and symptoms of toxicity:
not examined
Dermal irritation:
not examined
Conclusions:
Within JP-8, the rank order of absorption for all marker components was (mean +/- SEM; % dose) naphthalene (1.17 +/- 0.07)> dodecane (0.63 +/- 0.04) > hexadecane (0.18 +/- 0.08).  The area under the curve (AUC) was determined to be (mean +/- SEM; % dose-h/mL): naphthalene (0.0199 +/- 0.0020)> dodecane (0.0107 +/- 0.0009) > hexadecane (0.0017 +/- 0.0003). In contrast, deposition within dosed skin showed the reverse pattern.
Executive summary:

The percutaneous absorption and cutaneous disposition of topically applied neat Jet-A, JP-8, and JP-8(100) jet fuels (25 uL/5 cm2) was examined by monitoring the absorptive flux of the marker components 14C naphthalene and 4H dodecane simultaneously applied non-occluded to isolated perfused porcine skin flaps (a = 4). Absorption of 14C hexadecane was estimated from JP-8 fuel. Absorption and disposition of naphthalene and dodecane were also monitored using a nonvolatile JP-8 fraction reflecting exposure to residual fuel that might occur 24 h after a jet fuel spill. In all studies, perfusate, stratum corneum, and skin concentrations were measured over 5 h. Naphthalene absorption had a clear peak absorptive flux at less than 1 h, while dodecane and hexadecane had prolonged, albeit significantly lower, absorption flux profiles. Within JP-8, the rank order of absorption for all marker components was (mean +/- SEM; % dose) naphthalene (1.17 +/- 0.07) > dodecane (0.63 +/- 0.04) > hexadecane (0.18 +/- 0.08).  The area under the curve (AUC) was determined to be (mean +/- SEM; % dose-h/mL): naphthalene (0.0199 +/- 0.0020) > dodecane (0.0107 +/- 0.0009) > hexadecane (0.0017 +/- 0.0003). In contrast, deposition within dosed skin showed the reverse pattern.

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
supporting study
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: supporting information
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
Deviations:
no
GLP compliance:
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
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.
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 I 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
Executive summary:

The flux of hexadecane for human skin was determined to be 7.02 +/- 0.00 (nmol/cm2/h) x 10E-3. The permeability coefficient (Kp), of hexadecane for human skin were determined to be 3.60 +/- 0.00 (cm/h) x 10E-3. The binding for hexadecane in human skin was 1.53 +/-0.27. 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.

Endpoint:
dermal absorption in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
2003
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: supporting information
Executive summary:

The percutaneous absorption and dermal toxicity was determined for three components of JP-8 (i.e., xylene, heptane, and hexadecane) in vivo in weanling pigs. In vivo percutaneous absorption results suggest a greater absorption of hexadecane (0.43%) than xylene (0.17%) or heptane (0.14%) of the applied dose after 30 min exposure. Transepidermal water loss (TEWL) provides a robust method for assessing damage to the stratum corneum. Heptane showed greater increase in TEWL than the other two chemicals. No significant (p < 0.05) increase in temperature was observed at the chemically treated site than the control site. Heptane showed greater TEWL values and erythema score than other two chemicals (xylene and hexadecane). Erythema was completely resolved after 24 h of the patch removal in case of xylene and hexadecane.

Description of key information

Short description of key information on bioaccumulation potential result:

C14-C20 aliphatic, 2-20% aromatic hydrocarbon fluids are typically metabolized by side chain oxidation to alcohol and carboxylic acid derivatives. These metabolites can be glucuronidated and excreted in the urine or further metabolized before being excreted. The majority of the metabolites are excreted in the urine and to a lower extent, in the feces. Excretion is rapid with the majority of the elimination occurring within the first 24 hours of exposure. As a result of the lack of systemic toxicity and the ability of the parent material to undergo metabolism and rapid excretion, bioaccumulation of the test substance in the tissues is not likely to occur.

Short description of key information on absorption rate:

C14-C20 aliphatic, 2-20% aromatic hydrocarbon fluids are poorly dermally absorbed and they tend to partition into the stratum corneum. When dermally absorbed, C14-C20 aliphatic, 2-20% aromatic hydrocarbon fluids are rapidly metabolized and eliminated.

Key value for chemical safety assessment

Additional information

C14–C20 aliphatic, 2 -30% aromatic hydrocarbon fluids are readily absorbed when inhaled or ingested.  C14–C20 aliphatic, 2 -30% aromatic hydrocarbon fluids are poorly dermally absorbed. Regardless of exposure route, C14–C20 aliphatic, 2-30% aromatic hydrocarbon fluids are rapidly metabolized. Bioaccumulation of C14–C20 aliphatic, 2 -30% aromatic hydrocarbon fluids is not expected.

READ ACROSS STRATEGY

Substances in the C14-C20 aliphatic [2-30% Aromatics] Hydrocarbon solvent category are mixed solvents of variable composition, containing primarily aliphatic constituents with up to 30% aromatic constituents. The hydrocarbon solvents which are compositionally most closely related are the category 3 substances (C9-C14 aliphatic [2-25% aromatics]. These substances consist of molecules which are of similar types and proportions to those in category 4 but are of lower molecular weight. The toxicological principle which supports read across to category 4 from category 3 is that substances of similar composition are likely to have similar toxicological properties.

 

The other types of substances which may also be useful for read across are petroleum substances of similar carbon number and in aromatic content, principally kerosene and jet fuel which, as noted above, are typically in the range of C9-C16. These substances also contain similar types of molecules in similar proportions to those in category 4. In general hydrocarbon solvents are more highly refined than petroleum substances. Accordingly, the petroleum substances typically represent a “worse case” with respect to hydrocarbon solvents and can be used for read across on that basis. 

Discussion on bioaccumulation potential result:

C14-C20 aliphatic, 2-20% aromatic hydrocarbon fluids are absorbed if ingested. C14-C20 aliphatic, 2-20% aromatic hydrocarbon fluids undergo metabolism and rapid excretion and low deposition, bioaccumulation of the test substance in the tissues is not likely to occur. 

The fate of pristane (2, 6, 10, 14-tetramethylpentadecane) was studied in rats after a single administration of 3H-labeled pristane. The balance study showed extensive fecal excretion (66%) mainly as unchanged hydrocarbon, whereas about 14% of ingested pristane was excreted in urine as pristane metabolites and tritiated water. After one week, 8.3% of the ingested 3H still was stored in the carcass and the radioactive distribution in tissues and organs showed a preferential incorporation into adipose tissue and liver. Over 75% of the radioactivity stored in the carcass was associated with pristane metabolites and tritiated water. Tissue metabolites were characterized by thin layer chromatography, gas chromatography, and mass spectrometric analyses. Four metabolites were identified: pristan-1-ol, pristane-2-ol, pristanic acid and 4, 8, 12-trimethyltridecanoic acid. These results demonstrated that pristane undergoes subterminal hydroxylation or terminal oxidation followed by the classical beta-oxidation process.

 

Labeled paraffins with 8-18 C atoms prepared from unsaturated hydrocarbons by addition of deuterium were added in oily solution to normal rats’ food. After six days an increase of deuterium content in the body fluid of all the rats was observed indicating that the labeled compounds had been metabolized. Deuterium was found in fatty acids of body fats and in liver lipids, especially for octadecane and hexadecane. Isolating oleic, stearic, and palmitic acids containing deuterium, indicated that methyl- and beta-oxidation of these hydrocarbons has occurred. Fatty acids resulting from metabolism of hydrocarbons with shorter chains were not deposited, but in these cases the urine contained fatty acids with higher deutrium content than after administration of octadecane and hexadecane. According to the deuterium content of the neutral fractions from liver and body lipids, all hydrocarbons tested were deposited to only a small extent. The largest depots mainly occurred after feeding with octadecane and hexadecane.

 

Discussion on absorption rate:

There have not been any in vivo dermal absorption studies of C14-C20 aliphatic, 2-20% aromatic hydrocarbon fluids, but there have been in vitro and in vivo studies for constituents of the C14-C20 aliphatic, 2-20% aromatic hydrocarbon fluids.  Due to the structural similarity of these molecules to other constituents of the C14 – C20 aliphatic, 2-20% aromatic hydrocarbon fluids, it seems reasonable to assume that the solvents would have toxicokinetic properties similar to those of these constituents.  

 

IN VIVO

 

The percutaneous absorption and cutaneous disposition of topically applied neat Jet-A, JP-8, and JP-8(100) jet fuels (25 uL/5 cm2) was examined by monitoring the absorptive flux of the marker components 14C naphthalene and 4H dodecane simultaneously applied non-occluded to isolated perfused porcine skin flaps (a = 4). Absorption of 14C hexadecane was estimated from JP-8 fuel. Absorption and disposition of naphthalene and dodecane were also monitored using a nonvolatile JP-8 fraction reflecting exposure to residual fuel that might occur 24 h after a jet fuel spill. In all studies, perfusate, stratum corneum, and skin concentrations were measured over 5 h. Naphthalene absorption had a clear peak absorptive flux at less than 1 h, while dodecane and hexadecane had prolonged, albeit significantly lower, absorption flux profiles. Within JP-8, absorption was (mean +/- SEM; % dose) hexadecane (0.18 +/- 0.08).  The area under the curve (AUC) was determined to be (mean +/- SEM; % dose-h/mL): hexadecane (0.0017 +/- 0.0003).

 

IN VITRO

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.

 

The percutaneous absorption was determined in vivo (weanling pigs) for the constituent hexadecane, which is also a component of JP-8. In vivo percutaneous absorption results suggest a greater absorption of hexadecane (0.43%) than xylene (0.17%) or heptane (0.14%) of the applied dose after 30 min exposure. Transepidermal water loss (TEWL) provides a robust method for assessing damage to the stratum corneum. Heptane showed greater increase in TEWL than the other two chemicals. No significant (p < 0.05) increase in temperature was observed at the chemically treated site than the control site. Heptane showed greater TEWL values and erythema scores than other two chemicals (xylene and hexadecane). Erythema was completely resolved after 24 h of the patch removal in case of xylene and hexadecane.

OVERVIEW of PERCUTANEOUS ABSORPTION OF HYDROCARBON SOLVENTS

There are no studies of repeated dose toxicity of hydrocarbon solvents using the dermal route of administration. Accordingly, where it is necessary to calculate dermal DNELs, systemic data from studies utilizing other routes of administration, normally inhalation but also oral data, can be used in some situations.  In accordance with ECHA guidance, read across from oral or inhalation data to dermal should account for differences in absorption where these exist (R8, example B.6). In fact, hydrocarbon solvents are poorly absorbed in most situations, in part because some are volatile and do not remain in contact with the skin for long periods of time and also because, due to their hydrophobic natures, do not partition well into aqueous environments and are poorly absorbed into the blood. 

 

If these differences in relative absorption are introduced into the DNEL calculations to calculate external doses, the DNELs based on systemic effects are highly inflated. This seems potentially misleading as it implies that substances have different intrinsic hazards when encountered by different routes whereas in fact the differences are due ultimately to differences in absorbed dose. Accordingly, it is our opinion that it would be more transparent if the differences in absorption were taken into account in the exposure equations rather than in DNEL derivation. 

 

Shown below is a compilation of percutaneous absorption information for a number of hydrocarbon solvent constituents covering carbon numbers ranging from C5 to C14 as well as examples of both aliphatic and aromatic constituents. The low molecular weight aliphatic hydrocarbons (n-pentane, 2-methylpentane, n-hexane, n-heptane, and n-octane) were tested by Tsuruta (1982) using rat skin in an in vitro model system. As shown (Table 1), the highest percutaneous absorption value was 2 ug/cm2/hr for pentane. Lower values (< ~ 1 ug/cm2/hr) were reported for aliphatic hydrocarbons ranging from hexane to octane. Several authors have assessed the percutaneous absorption of higher molecular weight aliphatic constituents including Baynes et al. (2000), Singh and Singh (2003), Muhammad et al. (2005), and Kim et al., (2006). The first three of these authors used porcine skin models and reported that, except for one anomalous result with tridecane, the percutaneous absorption values for aliphatic constituents ranging from nonane to tetradecane were well below 1 ug/cm2/hr. Rat and human skin are considered to be more permeable than human skin (Kim et al., 2006), so these numbers can be considered conservative. 

 

Kim et al. (2006) reported results of percutaneous absorption studies with human skin under in vivo conditions. In this case, the assessment method was based on tape stripping. The authors reported percutaneous absorption values ranging from 1 – 2 ug/kg/day for decane, undecane and dodecane. These values are higher than those reported by other authors, most likely because this technique measures absorption into the skin but not through the skin as was done in the studies listed above. Accordingly, it seems likely that these numbers are conservative as well.

With respect to aromatic hydrocarbons, most of the reported percutaneous absorption values [Baynes et al. (2000); Singh and Singh (2003); Mohammad et al. (2005); and Kim et al. (2006)] are less than 2 ug/cm2/day. The only exceptions are the values for naphthalene from Mohammad et al. (2005) which range from 4.2-6.6 ug/cm2/hr. 

 

After considering all of the above, it seems reasonable to assume apparent that across the entire range of hydrocarbon solvent constituents, percutaneous absorption values are less than 2 ug/cm2/day. Accordingly, when systemic dermal DNELs are calculated using route to route extrapolations, the values will not be corrected for differences in absorption. Rather, 2 ug/cm2/hr will be used as a common percutaneous absorption rate for all hydrocarbon solvents for which dermal exposure estimates are provided. 

           

Table 1: Summarized information on percutaneous absorption of hydrocarbon solvent constituents (C5-C16). 

 

Constituent

Molecular Weight

nmol/min/cm2

nmol/hr/cm2

ug/cm2/hr

Reference

Aliphatic Constituents

 

 

 

 

 

Pentane

72

0.52

31.2

2.2

Tsuruta et al. 1982

 

 

 

 

 

 

2-methyl pentane

86

0.02

1.2

0.1

Tsuruta et al., 1982

 

 

 

 

 

 

n-hexane

86

0.02

0.6

0.5

Tsuruta et al., 1982

 

 

 

 

 

 

n-heptane

100

0.02

1.2

0.1

Tsuruta et al., 1982

 

 

 

 

 

 

n-octane

114

0.08 x 10-3

0.005

0.0005

Tsuruta et al., 1982

 

 

 

 

 

 

Nonane

128

 

 

0.03

Muhammad et al., 2005

Nonane

 

 

 

0.38

McDougal et al., 1999

 

 

 

 

 

 

Decane

142

 

 

2

Kim et al., 2006

Decane

 

 

 

1.65

McDougal et al., 1999

 

 

 

 

 

 

Undecane

156

 

 

0.06-0.07

Muhammad et al., 2005

Undecane

 

 

 

1.0

Kim et al., 2006

Undecane

 

 

 

1.22

McDougal et al., 1999

 

 

 

 

 

 

Dodecane

170

 

 

0.02-0.04

Muhammad et al., 2005

Dodecane

 

 

 

2

Kim et al., 2006

Dodecane

 

 

 

0.3

Singh and Singh, 2003

Dodecane

 

 

 

0.51

McDougal et al., 1999

Dodecane

 

 

 

0.1

Baynes et al. 2000

 

 

 

 

 

 

Tridecane

184

 

 

0.00-0.02

Muhammad et al., 2005

Tridecane

 

 

 

2.5

Singh and Singh, 2003

Tridecane

 

 

 

0.33

McDougal et al., 1999

Tetradecane

198

 

 

0.3

Singh and Singh, 2003

Hexadecane

 

 

7.02 x 10E-3

0.00004

Singh and Singh, 2002

 

 

 

 

 

 

Aromatic Constituents

 

 

 

 

 

Trimethyl benzene

120

 

 

0.49 - 1.01

Muhammad et al., 2005

Trimethyl benzene

 

 

 

1.25

McDougal et al., 1999

 

 

 

 

 

 

Naphthalene

128

 

 

6.6 - 4.2

Muhammad et al., 2005

Naphthalene

 

 

 

0.5

Kim et al., 2006

Naphthalene

 

 

 

1.4

Singh and Singh 2002

Naphthalene

 

 

 

1.8

Baynes et al. (2000)

Naphthalene

 

 

 

1.0

McDougal et al., 1999

 

 

 

 

 

 

1 methyl naphthalene

142

 

 

0.5

Kim et al., 2006

Methyl naphthalene

 

 

 

1.55

McDougal et al., 1999

 

 

 

 

 

 

2-methyl naphthalene

 

 

 

0.5

Kim et al., 2006

2-methyl naphthalene

 

 

 

1.1

Singh and Singh, 2002

 

 

 

 

 

 

 

 

 

 

 

 

Dimethyl naphthalene

156

 

 

0.62 – 0.67

Muhammad et al., 2005

Dimethyl naphthalene

 

 

 

0.59

McDougal et al. 1999

 

References

Tsuruta, H. et al. (1982). Percutaneous absorption of organic solvents III. On the penetration rates of hydrophobic solvents through the excised rat skin. Industrial Health 20:335-345.

 

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