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Additional information

There are no data available on genetic toxicity of Distillates (Fischer-Tropsch), 210-360 degree Celsius, hydrotreated, isoalkanes, cyclics, <0.1% aromatics.

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).

 

Genetic toxicity: in-vitro

The mutagenic potential of hydrocarbons, C14-C18, n-alkanes, isoalkanes, cyclics, < 2% aromatics was assessed in the Ames test according to OECD 471 and in compliance with GLP (Marzin, 1994). The histidine-requiring S. typhimurium mutants TA 1535, TA 1537, TA 102, TA 98 and TA 100 were used in the presence and the absence of metabolic activation system from the liver fraction of Aroclor 1254-induced rats (S9-mix). Each strain was exposed to 5 dose levels according to the direct incorporating plate method. After 48 hours of incubation at 37 °C, the revertant colonies were scored. A preliminary toxicity assay was performed according to the direct incorporating method to define the 5 dose levels to be used in the main test. The evaluation of toxicity was performed on the basis of the observation of the decrease in the number of revertant colonies. The test substance was tested in the main experiment according to two tests independently performed in the same way as the range-finding test. The test substance was diluted in 10% Pluronic F68 aqueous solution. Dose levels used in the main assay were 2, 6, 20, 60 and 200 µL/plate in the main test, with and without S9-mix. All determinations were made in triplicate. Simultaneous negative (solvent, triplicate) and positive controls (triplicate) were used in all experiments. No toxicity was observed in any of the strains in the absence and in the presence of S-9 mix up to the highest dose tested in the main test (62.4% to 102.2% survival). No increase in revertant mean number was observed in any S. typhimurium strain with and without S9-mix in the preliminary test and in the first main test. Positive controls gave the expected increases in the number of revertants, with and without S-9 mix.

Both statistically significant results and biologically significant results (two-fold increase by comparison with solvent) were observed at the highest test substance dose in S. typhimurium TA 98 but without a dose-effect relationship. Reduced but statistically significant positive results were also observed in S. typhimurium TA 100 with a dose-effect relationship. However, no biological significance was observed at any dose. A third test was performed in S. typhimurium TA 98 and TA 100 under the same conditions as the second main test. In this case the positive results obtained in the previous main test were not observed in either S. typhimurium TA 98 or TA 100. In the absence of reproducible results, the test substance was not considered as mutagenic in S. typhimurium according to the decision criteria of Brusick (1980). Under the conditions of this study, test substance did not demonstrate any in-vitro mutagenic activity in this bacterial test system.

Hydrocarbons, C10-C13, n-alkanes, isoalkanes, cyclics, < 2% aromatics were also examined for mutagenic activity in the Ames test using histidine-requiring Salmonella typhimurium strains TA 1535, 1537, 98 and 100 and the tryptophan requiring E.coli strain WP2 uvrA, in the absence and presence of a liver S9 fraction for metabolic activation (Shell, 1998).  Two tests were performed: Test 1 (8, 40, 200, 1000, 5000 µg/plate), Test 2 (1000, 2000, 3000, 4000, 5000 µg/plate).  The material was not cytotoxic.  In all cases, the test substance did not induce any significant changes in the number of revertant colonies, with or without metabolic activation. Therefore, it is concluded in this study that the test substance is not a mutagenic agent. 

 

In an in-vitro chromosome aberration test, Chinese Hamster Ovary cells were exposed tohydrocarbons, C12-C16, n-alkanes, isoalkanes, cyclics, < 2% aromaticsat concentrations of 3.13, 6.26, 9.35 and 12.5 µg/mL for 10-h harvest and 12.5, 25, 37.5, 50 and 75 µg/mL for 20-h harvest, for 7 and 17 h, without metabolic activation and 37.5, 93.8, 188, 281, 375, 563 and 750 µg/mL for 10 and 20-h harvest, for 2 h, with metabolic activation (ExxonMobil, 1991).

Positive controls (mitomycin C without metabolic activation and cyclophosphamide with metabolic activation) induced the appropriate response. As there was no evidence of chromosome aberration induced over background, test substance is not mutagenic.

The potential of hydrocarbons, C11-C14, n-alkanes, isoalkanes, cyclics, < 2% aromatics to cause chromosome aberration was investigated in cultured human lymphocytes with and without the metabolic activation S9 system (Shell, 1998). Negative and positive control substances were include in both experiments to confirm the activity and sensitivity of the test systems.  In the first experiment, the maximum dose levels selected for chromosome analysis were 82.34 µg/ml and 1000 µg/ml, in the absence and presence of S9 respectively. These dose levels caused inhibitions of the mitotic index of 57% and 30% respectively.  In the second experiment, the highest concentration used for chromosome analysis were 35.18 µg/ml and 1000 µg/ml in the absence and presence of S9-mix respectively, these gave a reduction in the mitotic index of 52% and 12% respectively.  In both Experiments 1 and 2 in the presence of S9; and in Experiment 2 in the absence of S9-mix only there were no significant increases in the frequency of the cells with structural aberrations in cultures treated with the test substance. Following treatment in Experiment 2 in the absence of S9-mix there was a significant increase in the frequency of structural aberrations at the lowest dose analyzed (22.52 µg/ml). Additional doses from Experiment 1 were analysed (19.79 and 28.25 µg/ml) to confirm whether this effect was only apparent at low concentrations.  No increase in the frequency of structural aberrations was apparent at these concentrations.  In order to further clarify the findings seen in the initial experiments, a third experiment was performed in which there were no significant increases in the frequency of cells with structural aberrations in all cultures treated with test substance.  Since the increase in structural aberrations seen at 22.52 µg/ml in Experiment 2 was not apparent in other experiments at similar or higher concentrations, the effect was considered to be non-reproducible and of no biological importance.  Based on these results, it is concluded that test substance did not induce chromosome aberrations in cultured lymphocytes when tested to its limit of toxicity in both the absence and presence of S9-mix.

 

In the study of the Chevron Philips Chemical Company (1982), the potential of C10-C13, isoalkanes to induce gene mutations in L5178Y mouse lymphoma cells at the T/K locus study was assessed. Appropriate negative, solvent, and positive controls were included with each assay. The test concentrations were determined by a preliminary range finding study with the highest concentration targeted to give approximately fifty to ninety percent inhibition of suspension cell growth depending on the solubility of the compound. The test substance achieved a homogeneous mixture at approximately 100 mg/mL in dimethylsulfoxide. The maximum concentration selected for the mutagenicity test was 1000 µg/mL because it represents the limits of solubility of the test substance. Exposure to 8 test concentrations upt to 1000 µg/mL in the presence and in the absence of metabolic activation did not increase the induction of forward mutations in L5178Y mouse lymphoma cells at the T/K locus. Therefore, the test substance was not considered to be mutagenic in this test system.

 

Genetic toxicity: in-vivo

Hydrocarbons, C10-C13, n-alkanes, isoalkanes, cyclics, < 2% aromatics wereexamined for its potential to induce chromosomal damage in bone marrow erythrocytes in mice dosed by oral gavage at concentrations of 5.0,2.5, and 1.25 g/kg (ExxonMobil, 1991). Vehicle and positive control animals received corn oil and cyclophosphamide, respectively.  Bone marrow samples were collected and evaluated for micronucleus formation 24, 48 and 72 hours after dosing.  The test substance did not induce a statistically significant change in the PCE/NCE ratio in any of the test material dose groups when compared to their concurrent vehicle control groups. The positive control material (cyclophosphamide) produced a marked increase in the frequency of micronucleated PCE when compared to the concurrent vehicle control group. The test substance was considered to be non-genotoxic and non-clastogenic under the conditions of the test.

 

Based on the read-across using an analogue approach, these results suggest that hydrocarbons, C11-C19, isoalkanes, cyclics, < 2% aromatics are not expected to induce genotoxicity in-vitro and in-vivo.

 


Short description of key information:
Based on read-across using the analogue approach, Distillates (Fischer-Tropsch), 210-360 degree Celsius, hydrotreated, isoalkanes, cyclics, <0.1% aromatics are not considered to be genotoxic.

Genetic toxicity: in-vitro
RA with C14-C18: Gene mutation (equivalent to OECD 471): negative with and without metabolic activation
RA with C10-C13: Gene mutation (equivalent to OECD 471): negative with and without metabolic activation
RA with C12-C16: Chromosome aberration (equivalent to OECD 473, CHO cells): negative with and without metabolic activation
RA with C11-C14: Chromosome aberration (equivalent to OECD 473, human lymphocytes): negative with and without metabolic activation
RA with C10-C13: Gene mutation (equivalent to OECD 476, MLA): negative with and without metabolic activation

Genetic toxicity: in-vivo
RA with C10-C13: Chromosome aberration (equivalent to OECD 474): negative in CD-1 mice

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on read-across within an analogue approach, the available data on genetic toxicity do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.