Kerosine (Fischer-Tropsch), full-range, C8-16-branched and linear

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

750 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

The available information meets fully the tonnage-driven data requirement of REACH. The study was performed on the test substance 'Distillates (Fischer-Tropsch), C8-26 - branched and linear', which is produced using the same Fischer-Tropsch process as 'Distillates (Fischer-Tropsch), C8-16 - branched and linear' and contains all of the same hydrocarbon constituents. This is a foreseen alternative under REACH in order to avoid unnecessary animal testing. The study was conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions. So it can be considered to be reliable with minor restrictions.
Therefore, the database is of good quality, i.e. sufficient to meet the data requirements under REACH.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

No reproductive toxicity data are available for GTL Kerosine ( Kerosine (Fischer-Tropsch), full range, C8-16 - branched and linear). A two-generation reproductive toxicity study (oral, gavage) has been carried out using the related substance, GTL Diesel (C8-C26, branched and linear, CAS 848301-67-7), following OECD Test Guideline 416 and conducted according to GLP (Faiola, 2011). GTL Diesel contains all constituents that are present in GTL Kerosine. The test material was administered by gavage to three groups of male and female Crl:CD (SD) rats, each of 25 and 28 animals of each sex for the F₀and F₁generations, respectively. Test concentrations were 0 (control), 50, 200 and 750 mg/kg bw/day for the F₀and F₁generations. Dosing was performed for 70 consecutive days prior to mating. Males continued to be dosed during the 14-day mating period and post-mating holding. Females were dosed during the mating period, gestation and lactation.

Administration of GTL Diesel to male and female rats at dosages up to 750 mg/kg/day had no effect on reproductive performance or gestation length and parturition of both the F0and F1parental generations. In addition, there were no test item-related effects on F1and F2 litter parameters, postnatal survival, physical condition/mortality, anogenital distance, and pup body weights. Vaginal patency of F1females was unaffected by test item administration. There was a statistically significant, test article-related increase in the mean age and adjusted age of attainment of balanopreputial separation in F1males given 750 mg/kg/day. However, this change was not considered adverse, as the age and adjusted age of attainment fell within the historical control data range for this parameter. Reproductive performance parameters (mating and fertility indices) for F1males given 750 mg/kg/day, although slightly lower than the control group, were not statistically significantly different from the control group and also fell within the historical control data range. In addition, andrology parameters and sperm morphology data for the individual F1males in the high-dose group, with the longest delay in attainment of balanopreputial separation, were similar to the group mean data, further supporting the conclusion that the delay in preputial separation was non-adverse. Sperm morphology assessments of F1males showed a statistically significant increase in the percent of abnormal sperm in those males given 750 mg/kg/day; however, this change was not observed in F₀males and resulted primarily from a single male, and was therefore considered equivocal and non-adverse since the percent of abnormal sperm seen fell within the historical control data range for this parameter. Reproductive performance parameters (mating and fertility indices) for F1males given 750 mg/kg/day were unaffected, and there were no microscopic findings in the testes. Based on the absence of adverse, test item-related findings on the integrity and performance of the male and female reproductive systems, a dosage level of 750 mg/kg/day was considered to be the no-observed-adverse-effect level (NOAEL) for reproductive toxicity.

Short description of key information:
Reproductive toxicity: Subchronic study oral (gavage), rat (Crl:CD (SD)) m/f (OECD guideline 416, GLP): NOAEL: 750 mg/kg bw/day (male/female, highest dose tested)

Justification for selection of Effect on fertility via oral route:
Only one study available.
However, the study was conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. Additionally, although stated as "supporting substance", the test substance (C8-C26 carbon chain length) covers fully the carbon chain length range of the registered substance and does therefore sufficiently cover the detection of all possible effects arinsing from the C8-16 derivatives. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Effects on developmental toxicity

Description of key information

Reproductive toxicity: Subchronic, Two-Generation study oral (gavage), rat (Crl:CD (SD)) m/f (OECD guideline 416, GLP): NOAEL: 750 mg/kg bw/day (male/female, F1/F2 litters, highest dose tested)

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

750 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

The available information meets fully the tonnage-driven data requirement of REACH.
A two-generation reproductive toxicity study was performed on the test substance 'Distillates (Fischer-Tropsch), C8-26 - branched and linear', which is produced using the same Fischer-Tropsch process as 'Distillates (Fischer-Tropsch), C8-16 - branched and linear' and contains all of the same hydrocarbon constituents. This is a foreseen alternative under REACH in order to avoid unnecessary animal testing. It demonstrated an absence of developmental effects in both F1 and F2 litters at the highest dose tested. Traditional endpoints for evaluation of developmental toxicity are hence included and a separate developmental study can be avoided.
The study was conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions. So it can be considered to be reliable with minor restrictions.
Therefore, the database is of good quality, i.e. sufficient to meet the data requirements under REACH.

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

In a two-generation reproductive toxicity study (OECD 416) with GTL Diesel (Faiola, 2011), there were no test item-related effects on F1and F2litter parameters, postnatal survival, physical condition, mortality, pup body weights and anogenital distance. Equivocal, non-adverse decreases (not statistically significant) in absolute and relative spleen weights were observed in the F1and F2male and female PND 21 pups in the group given 750 mg/kg/day, compared with the control group. Macroscopic and microscopic findings in PND 21 pups were not test item related. Further details are presented in Sections 5.6 and 5.9.1. Based on this study, NOAEL for developmental effects can therefore be considered to be at least 750 mg/kg bw/day (the highest dose tested).

Justification for selection of Effect on developmental toxicity: via oral route:
A separate developmental study can be avoided because reliable data from a two-generation reproductive toxicity is available (See: Effects on fertility: via oral route):
The two-generation reproductive toxicity study with GTL Diesel (see IUCLID section 7.8.1, Distillates (Fischer-Tropsch), full range, C8-26 - branched and linear), demonstrated an absence of developmental effects in both F1 and F2 litters at the highest dose tested. Traditional endpoints for evaluation of developmental toxicity are hence included. Based on this study, the NOAEL for developmental effects can therefore be considered to be at least 750 mg/kg bw/day.

Justification for classification or non-classification

A reliable two-generation study (OECD 416) is available on 'Distillates (Fischer-Tropsch), full range, C8-26 - branched and linear'. This substance is produced using the same Fischer-Tropsch process as 'Distillates (Fischer-Tropsch), C8-16 - branched and linear' and contains all of the same hydrocarbon constituents, but the product fraction additionally contains longer carbon chain lengths, up to C26, compared to C16 in 'Distillates (Fischer-Tropsch), C8-16 - branched and linear'. It hence serves perfectly as a surrogate for 'Distillates (Fischer-Tropsch), C8-16 - branched and linear' and the results can be used for classification.

Administration of 'Distillates (Fischer-Tropsch), full range, C8 -26 - branched and linear' to male and female rats at dosages up to 750 mg/kg/day had no effect on reproductive performance or gestation length and parturition of both the F0 and F1 parental generations. In addition, there were no test item-related effects on F1 and F2 litter parameters, postnatal survival, physical condition/mortality, anogenital distance, and pup body weights.

So, no evidence for reproductive or developmental toxicity of 'Distillates (Fischer-Tropsch), C8-16 - branched and linear' was detected up to the highest tested dose of 750 mg/kg bw/day. and consequently, it does not need be classified, neither according 1272/2008/EC nor 67/548/EEC.