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Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
750 mg/kg bw/day
Additional information

There are no reproduction toxicity studies for Hydrocarbons, C16-C22, n-alkanes, isoalkanes, <2% aromatics. However, there are studies available for GTL Gasoil (C8-C26) and GTL Base Oil Distillates (C18-C50). Thus, based on the similarity of constituents and carbon-range coverage, read-across is justified.

GTL Gasoil (C8 - C26, branched and linear)

A two-generation reproductive toxicity study (oral, gavage) has been carried out using GTL Gasoil (C8-C26, branched and linear, CAS 848301-67-7), following OECD Test Guideline 416 and conducted according to GLP (Faiola, 2011a). 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 Gasoil 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 F2litter 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.

GTL Base Oil Distillates (C18-C50, branched, cyclic and linear)

In a two-generation reproductive toxicity study (Faiola, 2011b),GTL Base Oil [0 (vehicle), 50, 250, or 1000 mg/kg/day)] was given orally to F0and F1parental male and female rats for at least 70 days prior to mating and throughout the 14-day mating, post mating holding (for males), and gestation and lactation (for females) periods. There was a test item-related, non-adverse decrease in Anogenital distance in F1females born from dams given 250 and 1000 mg/kg/day. Test item-related histopathological lesions were identified in the lungs (chronic interstitial/alveolus inflammation) of both males and females of the F0and F1generations with corresponding macroscopic findings and/or increased lung weights and the kidneys (renal tubule hyaline droplets likely representingα2μ-globulin) of the F1males only. The lung lesions were most likely secondary to aspiration of the test material and therefore not relevant for human risk assessment. The renal effects are a well-known male rat specific effect which is induced by hydrocarbons and has no relevance for humans. An equivocal, non-adverse slight decrease in F2pup brain weights was noted. Based on the absence of adverse, test item-related findings on the integrity and performance of the male and female reproductive systems, the absence of adverse findings directly attributable to the test item in non-reproductive tissues, and the absence of adverse effects on in-life parameters (such as body weight, feed consumption, and clinical observations), the dosage level of 1000 mg/kg/day was considered to be the no-observed-adverse-effect level (NOAEL) for reproductive and systemic toxicity.

 

Based on the available weight of evidence for related substances in the relevant carbon number range it can be concluded that Hydrocarbons, C16-C22, n-alkanes, isoalkanes, <2% aromatics is not reprotoxic at dose levels ≥750 mg/kg bw/day.


Short description of key information:
A two-generation reproductive toxicity study (OECD 416) was conducted with GTL Gasoil (C8-C26, branched and linear). In this oral gavage study (Faiola, 2011a), there were no effects on any reproductive parameters up to the highest dose tested, 750 mg/kg bw/day. In a similar study with GTL Base Oil Distillates (C18-C50, branched, cyclic and linear), there were no effects up to the highest dose tested, 1000 mg/kg bw/day (Faiola, 2011b).

Effects on developmental toxicity

Description of key information
Pre-natal developmental toxicity (OECD 414) and two-generation reproductive toxicity studies (OECD 416) were conducted with GTL Gasoil and GTL Base Oil Distillates. In these oral gavage studies (Dunster, 2014, Senn, 2014, Faiola, 2011a and Faiola, 2011b), there were no effects on any parameters examined in the F1 and F2 generations up to the highest doses tested, 750 mg/kg bw/day and 1000 mg/kg bw/day respectively. 
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
750 mg/kg bw/day
Additional information

No specific developmental toxicity studies are currently available for Hydrocarbons, C16-C22, n-alkanes, isoalkanes, <2% aromatics or related Fischer-Tropsch-derived substances. However, evidence from pre-natal developmental studies (OECD 414) and two-generation reproductive toxicity studies (OECD 416) conducted with GTL Gasoil (C8-C26) and GTL Base Oil Distillates (C18-C50) indicates that the substances are not developmental toxins at dose levels ≥750 and 1000 mg/kg bw/day.

GTL Gasoil (C8-C26, branched and linear)

A pre-natal developmental toxicity study in Sprague-Dawley rats was performed with GTL Gasoil (C8-C26) in accordance with OECD Test Guideline 414 and in compliance with GLP (Dunster, 2014). Four groups of 24 mated females were dosed once daily by gavage at dose levels of 0, 50, 200 and 750 mg/kg bw/day from Day 5 until Day 19 of gestation. There were no mortalities or test substance-related clinical findings at any dose level. There were no test substance-related changes in food consumption, water consumption or body weight. No treatment-related macroscopic abnormalities were detected at post mortem. There were no treatment-related effects on the uterine parameters examined, in foetal viability or in growth and development. No treatment-related effects were detected on external development or in the type and incidence of skeletal or visceral findings. The No Observed Adverse Effect Level for both parental females and for development was therefore considered to be 750 mg/kg bw/day.

In a two-generation reproductive toxicity study (OECD 416) with GTL Gasoil (Faiola, 2011a), 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).

GTL Base Oil Distillates (C18-C50, branched, cyclic and linear)

A pre-natal developmental toxicity study in Han Wistar rats was performed with GTL Base Oil Distillates (C18-C50) in accordance with OECD Test Guideline 414 and in compliance with GLP (Senn, 2014). Four groups of 22 mated females were dosed once daily by gavage at dose levels of 0, 50, 200 and 1000 mg/kg bw/day from Day 6 to Day 20post coitum. There were no mortalities or test substance-related clinical findings at any dose level. There were no test substance-related changes in food consumption, mean absolute body weight, body weight gain or corrected body weight gain. The number of post-implantation losses and number of foetuses per dam were not affected by treatment. There were no findings at any dose level during macroscopic examination. There were no test-substance related findings during external examination of the foetuses, and no effect on the sex ratio of the foetuses in any group. Mean body weights of live foetuses were slightly increased at 1000 mg/kg bw/day. This increase was not in the range of the historical control data and a treatment-related effect therefore could not be excluded. There were no test substance-related findings noted during external and fresh visceral examination or skeletal examination of the foetuses and no delay in the stage of ossification was observed. The study author concluded that there were no adverse effects on skeletal development up to and including 1000 mg/kg bw/day. In isolation, the increased mean body weight of live foetuses is not considered to be adverse and therefore the No Observed Adverse Effect Level is 1000 mg/kg bw/day.

Administration of GTL Base Oil Distillates in a two- generation reproductive toxicity study in male and female rats at dosages up to 1000 mg/kg/day had no effect on reproductive performance or gestation length and parturition of both the F0and F1parental generations(Faiola, 2011b).Andrology parameters for F0and F1males were unaffected by test item administration. In addition, there were no test item-related effects on F1and F2litter parameters, postnatal survival, physical condition/mortality, and pup body weights. Vaginal patency of F1females and balanopreputial separation in F1males were also unaffected by test item administration.Based on the absence of adverse, test item related findings a dosage level of 1000 mg/kg/day for developmental effects was considered to be the NOAEL.

Justification for classification or non-classification

Based on the available read-across data Hydrocarbons, C16-C22, n-alkanes, isoalkanes, <2% aromaticsis not classified for reproductive or developmental toxicity according to Regulation (EC) No 1272/2008.

Additional information

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