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

Endpoint summary

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 possess repeated dose toxicity via the oral and inhalation exposure route.
Oral (similar to OECD 408), 90 d, rat: NOAEL ≥ 1000 mg/kg bw 
Oral (similar to OECD 408), 90 d, rat: NOAEL ≥ 1000 mg/kg bw 
Inhalation (similar to OECD 413), 90d, rat: NOAEC ≥ 6000 mg/m³

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Study duration:

subchronic

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Study duration:

subchronic

Species:

rat

Additional information

There are no data available on repeated dose toxicity via the oral and inhalation exposure route 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).

 

Oral:

A 90-day subchronic study was conducted in rats to assess the toxicity of hydrocarbons, C11-C14, n-alkanes, isoalkanes, cyclics, < 2% aromatics (ExxonMobil, 1991). The test substance was administered by oral gavage at a dose of 0, 100, 500, or 1000 mg/kg 7 days per week for a period of 13 weeks.  The control animals received a carrier (corn oil) dose and a satellite group was dosed at 1000 mg/ kg, 7 days/week for 13 weeks and was then observed for reversibility, persistence or delayed occurrence of toxic effects for 28 days post-treatment.  Observations were made as to the nature, onset, severity, and duration of toxicological signs. There were no deaths attributed to the oral administration of the test substance (two control group females died prior to termination).  The majority of animals in all groups displayed no observable abnormalities during the test period.  The most frequently noted observations included broken/maloccluded incisors, alopecia, and scabs, all of which were considered incidental.  Body weight, food consumption, and hematology data displayed no biologically significant trends for either males or females during the test period.  The most remarkable finding was a treatment-related microscopic change in the liver of the mid-dose females and the high dose of both sexes.  This change was minor and is typical of an adaptive change probably related to the livers metabolism of large volumes of the test substance and was reversible upon microscopic evaluation of the tissues from the satellite recovery group. Microscopic changes were also observed in the male kidneys at all doses.  These changes are characteristic of kidney changes produced in male rats by hydrocarbons and are considered to be a male rat specific phenomenon without human significance. Based on the data recorded in this study, the NOAEL for the test substance is ≥ 1000 mg/kg bw/day.

Hydrocarbons, C10-C13, n-alkanes, isoalkanes, cyclics, < 2% aromatics were administered by oral gavage to rats at concentrations of 500, 2500 and 5000 mg/kg, 7 days a week for 13 weeks to assess the subchronic toxicity (ExxonMobil, 1991).  An additional group of animals, dosed at 5000 mg/kg/day, was held for 4 weeks to assess reversibility.  No treatment-related mortality was observed; however, male body weights were decreased while food consumption increased in the 2500 and 5000 mg/kg dose groups.  Liver weights were elevated in male and female rats at 2500 and 5000 mg/kg/day.  Adrenal weights were significantly increased in male and female rats at 5000 mg/kg and in female rats at 2500 and 5000 mg/kg.  Testes weights were elevated in male rats at 5000 mg/kg.  Kidney effects occurred in males at all dose levels, and are indicative of alpha-2µ-globulin nephropathy.  Alpha-2µ-globulin nephropathy, also known as hyaline droplet nephropathy, results from the formation of complexes with a naturally occurring protein (alpha-2µ-globulin) in the kidneys of male rats.  These complexes can accumulate in the proximal renal tubule and may produce species-specific histopathological changes.  These kidney effects are specific to male rats and are not considered to be of biological relevance to humans.

Dose-related changes in hematology or serum chemistry parameters were observed and were consistent with the changes seen in the liver.  Histological findings of hepatocellular hypertrophy (liver cell enlargement) were seen in livers of both sexes in all dose groups.  These findings are believed to have been a compensatory response and not an indication of toxicity.  Additionally, these liver effects were reversible and occurred only at high doses that are not typical of hydrocarbon exposures for humans.  Other treatment-related effects were mucosal thickening and other signs of irritation of the stomach and anus which appear to be the direct result of high dose intubation of the locally irritating test substance.  These effects are believed to have been a compensatory response to local irritation and not an indication of toxicity.  All treatment-related effects were reversible within the 4-week recovery period.  Based on the results, the No Observed Adverse Effect Level (NOAEL) for the 90-day study was ≥ 5000 mg/kg/day.

 

Inhalation:

Hydrocarbons, C11-C14, n-alkanes, isoalkanes, cyclics, < 2% aromatics were administered by inhalation to albino rats for 6 hours/day, 5 days/week for 13 weeks at nominal vapor concentrations of 1500 mg/m³and 3000 mg/m³, and 6000 mg/m³to assess inhalation toxicity (Shell, 1980).  No mortality or treatment-related effects in any of the hematology and serum chemistry values were observed.  Liver and kidney weights were increased in male rats at all exposure levels, and liver weights were increased in female rats at 6000 mg/m³.  In addition, the male rats exposed to the test substance at all concentrations contained multiple, hyaline, intracytoplasmic, inclusion-droplets in the epithelium of the proximal convoluted tubules and showed an increased incidence of focal cortical, tubular basophilia.  The kidney effects observed in male rats are indicative of alpha-2µ-globulin nephropathy.  Alpha-2µ-globulin nephropathy, also known as hyaline droplet nephropathy, results from the formation of complexes with a naturally occurring protein (alpha-2µ-globulin) in the kidneys of male rats.  These complexes can accumulate in the proximal renal tubules and may produce species-specific histopathological changes.  These kidney effects are specific to male rats and are not considered to be of biological relevance to humans.  Histopathological examination did not reveal any abnormalities that were considered treatment related.  As there were no pathologic changes, changes in liver weight to body weight ratios mentioned above were judged to have been compensatory rather than toxic effects.  Based on these results, the No Observed Adverse Effect Concentration (NOAEC) was greater than or equal to 6000 mg/m³.

 

Hydrocarbons, C10-C12, isoalkanes, < 2% aromatics were administered by inhalation to albino rats for 6 hours/day, 5 days/week for 13 weeks at nominal vapor concentrations of 10400 mg/m³, 5200 mg/m³and 2600 mg/m³ to assess inhalation toxicity.  No mortality or treatment-related effects in any of the hematology and serum chemistry values were observed.  Liver and kidney weights were increased in male rats at all exposure levels, male heart weights were increased at the highest exposure level and liver and kidney weights were increased in female rats at 10400 mg/m³.  In addition, the male rats exposed to the test substance at all concentrations showed tubular degeneration and hyaline inclusion-droplets in the epithelium.  There was also scattered degeneration of the proximal renal tubules which showed cytoplasmic pallor and shrinkage. Occasionally the degenerate tubules were surrounded by a lymphocyte infiltrate. Many tubules also showed dilatation of the cortico-medullary junction, the dilated tubule being filled with a flocculent eosinophilic material. The kidney effects observed in male rats are indicative of alpha-2µ-globulin nephropathy.  Alpha-2µ-globulin nephropathy, also known as hyaline droplet nephropathy, results from the formation of complexes with a naturally occurring protein (alpha-2µ-globulin) in the kidneys of male rats.  These complexes can accumulate in the proximal renal tubule and may produce species-specific histopathological changes.  These kidney effects are specific to male rats and are not considered to be of biological relevance to humans.  Histopathological examination did not reveal any abnormalities that were considered treatment related.  As there were no pathologic changes, changes in organ weights mentioned above were judged to have been compensatory rather than toxic effects.  Based on these results, the No Observed Adverse Effect Concentration (NOAEC) was greater than or equal to 10400 mg/m³.

 

Justification for classification or non-classification

Based on read-across within an analogue approach, the available data on repeated dose toxicity (oral and inhalation) 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.