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

Endpoint summary

Description of key information

Short description of key information on bioaccumulation potential result: 
If C9-C14 aliphatic, < 2% aromatic hydrocarbon fluids are absorbed, they 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: 
C9-C14 aliphatic, < 2% aromatic hydrocarbon fluids are poorly absorbed dermally with an estimated overall percutaneous absorption rate of approximately 2ug/cm2/hr or 1% of the total applied fluid.  Regardless of exposure route, C9-C14 aliphatic, < 2% aromatic hydrocarbon fluids are rapidly metabolized and eliminated.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

There are no experimental studies available in which the toxicokinetic properties of Distillates (Fischer-Tropsch), 210-360 degree Celsius, hydrotreated, isoalkanes, cyclics, <0.1% aromatics were investigated.

Distillates (Fischer-Tropsch), 210-360 degree Celsius, hydrotreated, isoalkanes, cyclics, <0.1% aromatics consist of hydrocarbon solvents with predominant carbon numbers in the range of C11 to C19. The constituents of this solvent are single isomers as well as mixed solvents of which the primary constituents are branched chain (iso-), and cyclic aliphatic hydrocarbons. Aromatic constituents, if present, represent less than 0.1% of the total volume.

N-paraffins are only present in very low concentrations (<1%).

The carbon numbers in the range of C11 to C19 and initial distillation points (IBP) characterize the source substances. The distillation range of the source substances ranges from 220°C to 350 degree Celsius although some solvents may contain higher boiling material. The benzene and sulphur contents of source substances are low, benzene levels for example are typically <3 ppm.

The toxicology and environmental fate and effects data show that source substances have a similar order of (eco-)toxicological and environmental fate properties as the target substance. Therefore, read-across is performed based on an analogue approach (for details please refer to the analogue justification which is attached in section 13 of the technical dossier).

Basic toxicokinetic

Labeled paraffins with C8-C18 prepared from unsaturated hydrocarbons by addition of deuterium have been added in oily solution to normal rats’ food (Tulliez, 1977). 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 C18 and C16. 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 deuterium content than after administration of C18 and C16. 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 C18 and C16.

For n-alkanes > C9, no acute toxicity at saturated vapour concentrations and no evidence of acute central nervous system effects were found. In general, it is technically not possible for n-alkanes > C9, to achieve vapour concentrations (at 21.6 °C) which produce biological effects under acute conditions.

Inhaled n-alkanes C9-C13 are taken up into the blood and brain. However, uptake into both blood and brain decreases with increasing carbon number. In part this is because the vapour concentrations are reduced at increasing carbon number. There is also a corresponding reduction in the blood/air and brain/air ratios with increasing carbon numbers. Thus the efficiency of uptake into both blood and brain also decreases with increasing carbon number (Nilsen et al, 1988).

The aim of the study of Anand et al., 2007 was to determine in-vitro metabolic rate constants for semivolatile n-alkanes (C9, C10 and C14) by rat liver microsomal oxidation. The metabolism was assessed by measuring the disappearance of parent compound by gas chromatography. Various concentrations of n-alkanes were incubated with liver microsomes from adult male F-344 rats. Nonlinear kinetic constants for C9 and C10 were V(max) (nmol/mg protein/min) = 7.26 ± 0.20 and 2.80 ± 0.35 and K(M) (µM) = 294.83 ± 68.67 and 398.70 ± 42.70, respectively. Metabolic capacity as assessed by intrinsic clearance (V(max)/K(M)) was approximately four-fold higher for C9 (0.03 ± 0.005) than for C10 (0.007 ± 0.001). There was no appreciable metabolism of C14 even with higher microsomal protein concentration and longer incubation time. These results show a negative correlation between metabolic clearance and chain length of n-alkanes.

If hydrocarbon solvents are absorbed, they undergo metabolism, rapid excretion and low deposition. Bioaccumulation of hydrocarbons solvents in the tissues is not likely to occur.

Hydrocarbon solvents 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 h of exposure.

 

Dermal absorption

Three aliphatic (C12, C13, C14) chemicals, major components of JP-8, were investigated for changes in skin lipid and protein biophysics, and macroscopic barrier perturbation from dermal exposure (Singh S. and Singh, J., 2003). 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 C12, C13 and C14, 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 C12, C13 and C14, respectively. The permeability coefficients, Kp (cm/h)*10E-4, were 0.37 ± 0.13, 18.46 ± 1.50, 0.64 ± 0.20 for C12, C13 and C14, 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 C12, C13 and C14, respectively. The lag time was determined to be 1.33 ± 0.07, 0.89 ± 0.17, and 1.62 ± 0.34 hours for C12, C13 and C14, respectively. FTIR results suggest that all of the test chemicals significantly (P<0.05) extracted SC lipid and protein in comparison to control. C13 exhibited greater extraction of the SC lipid and protein as well as greater transport through the skin than other chemicals.

The flux, permeability coefficient (Kp), and binding of hexadecane for porcine and human skin was measured in a Franz diffusion cell (Singh et al., 2002). 1 mL of JP-8 jet fuel containing 0.5 µCi of 14C- labeled hexadecane was applied to the powdered skin (1.92 x 10E-4 mM/mL JP-8). The permeability coefficient and binding of hexadecane for porcine skin was determined to be 8.80 ± 0.00 (nmol/cm2/h) x 10E-3. The permeability coefficient 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 penetration and skin retention of C9, C12 and C14 was assessed in-vitro using hairless rats' skin (Babu et al., 2004). The effects of unocclusive dermal exposures of these chemicals (15 µL every 2 h for 8 h a day for four days) on the transepidermal water loss (TEWL) and erythema were measured in CD hairless rats. The expression of interleukin 1alpha (IL-1a) and TNF-alpha in the skin and blood were measured at the end of dermal exposures. The flux of C12 was 3- and 77-fold higher than C9 and C14. The retention of chemicals in stratum corneum (SC) was in the order of C14 > C12 > C9, and directly correlated to the log Kp (r2 = 0.9900) and molecular weight of the chemicals (r2 = 0.8782). The TEWL and erythema data indicate that irritation was in the following order: C14 > C12 > C9. Likewise, the expression of IL-la in the blood and TNF-alpha in the skin after dermal exposures was higher for C14 followed by C12 and C9 compared to control. In conclusion, the aliphatic hydrocarbon chemicals of the present study induced cumulative irritation upon low-level repeat exposures for a four-day period. The affinity of the chemicals to SC and their gradual accumulation in the skin in the present study is the probable cause for the differences in the skin irritation profiles of different aliphatic chemicals.

The aim of the study of Riviere et al. (1999) was to assess the percutaneous absorption and cutaneous disposition of topically applied (25 µL/5 cm2) neat Jet-A, JP-8, and JP-8(100) jet fuels by monitoring the absorptive flux of the marker components 14C-naphthalene and 4H-dodecane simultaneously applied non-occluded to isolated perfused porcine skin flaps (IPPSF) (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.

Taking into account all available data on surrogate substances, hydrocarbon fluids can be dermally absorbed, although they tend to partition into the stratum corneum. Regardless of exposure route, hydrocarbons fluids are rapidly metabolized and eliminated. Bioaccumulation of hydrocarbon fluids is not expected.