Distillates (Fischer-Tropsch), heavy, C18-50-branched, cyclic and linear

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Additional information

Distillates (Fischer-Tropsch), heavy, C18-50 - branched, cyclic and linear

In a two-generation reproductive toxicity study ‘Distillates (Fischer-Tropsch), heavy, C18-50 - branched, cyclic and linear’ [0 (vehicle), 50, 250, or 1000 mg/kg/day)] was given orally to F0 and F1 parental 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 F1 females 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 F0 and F1 generations with corresponding macroscopic findings and/or increased lung weights and the kidneys (renal tubule hyaline droplets likely representingα2μ-globulin) of the F1 males 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 F2 pup 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.

 

Distillates (Fischer-Tropsch), C8-C26 - branched and linear

A two-generation reproductive toxicity study (oral, gavage) has been carried out using the related substance ‘Distillates (Fischer-Tropsch), C8-C26 - branched and linear’, following OECD Test Guideline 416 and conducted according to GLP. 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 F0 and F1 generations, respectively. Test concentrations were 0 (control), 50, 200 and 750 mg/kg bw/day for the F0 and F1 generations. 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 the test material to male and female rats at dosages up to 750 mg/kg/day had no effect on reproductive performance or gestation lengthand 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. Vaginal patency of F1 females 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 F1 males 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 F1 males 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 F1 males 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 F1 males 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 F1 males 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:
1000 mg/kg/day was considered to be the no-observed-adverse-effect level (NOAEL) for reproductive and systemic toxicity.

Effects on developmental toxicity

Description of key information

As results of 2-generation study