Hydrocarbons, C13-C20, n-alkanes, isoalkanes, cyclic, aromatics (40-60%)

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Additional information

There are no reliable reproductive toxicity studies for C13-C20 n-alkanes, isoalkanes, cyclics, 40-60% aromatics. However, there were several studies located for analogous test materials, JP-8 fuel and hydrodesulfurized kerosene. Thus read-across was performed.

JP-8 fuel was examined for its reproductive toxicity to male and female rats in a one generation reproductive toxicity study, conducted similar to OECD 415 (Mattie et al., 2000). For the male reproductive toxicity study, male rats were given 0, 750, 1500 or 3000 mg/kg neat JP-8 daily by gavage for 70 days prior to and during mating with naive females. Since there were no significant differences in the sperm parameters examined and no adverse effects on pregnancy rate as well as gestation length, the reproductive NOAEL for male rats was set ≥ 3000 mg/kg/day, which was the highest dose tested. For the female reproductive toxicity study, female rats were dosed with neat JP-8 (0, 325, 750, 1500 mg/kg) daily by gavage for a total of 21 weeks (90-day plus mating with naive males, gestation and lactation) in order to assess general toxicity, fertility and reproductive endpoints. Based on the absence of tretment-related effects on pregnancy rate, gestation duration, litter size as well as percentage of live pups, the reproductive NOAEL for female rats is considered ≥ 1500 mg/kg/day, which was the highest dose tested. The F1 (fetus) NOAEL is set to be 750 mg/kg/day based on a decrease in body weight that correlated to a decrease in maternal body weight.

Hydrodesulfurized kerosene was examined in a reproduction / developmental toxicity screening test according to OECD 421 (Schreiner et al., 1997). Hydrodesulfurized kerosene was dermally administered at doses of 0 (vehicle), 165, 330, and 494 mg/kg/day to groups of male and female Sprague-Dawley rats. Based on the absence of effects, it was concluded that hydrodesulfurized kerosene did not induce reproductive toxicity in the parental animals, moreover no effects on the endocrine system were observed. Therefore, the NOAEL was determined to be ≥ 494 mg/kg bw/day.

Based on the available read-across data, C13-C20 n-alkanes, isoalkanes, cyclics, 40-60% aromatics are not expected to be reproductive toxicants.

Short description of key information:
Based on the weight of evidence of all available data, e. g. absence of adverse effects in male and female rats in reproductive toxicity studies performed similar to OECD 415 with JP-8 fuel and a screening study with hydrodesulfurized kerosene (according to OECD 421) as well as the incapability of Jet Fuel A to induce dominat lethal effects in mice (API, 1980), C13-C20 n-alkanes, isoalkanes, cyclics, 40-60% aromatics are not expected to be reproductive toxicants. Therefore, the NOAEL for reproductive effects is considered > 3000 mg/kg/day, which corresponds to the highest dose tested in the available studies.

Effects on developmental toxicity

Description of key information

OECD Guideline 414 (Prenatal Developmental Toxicity Study) - Oral Administration - The NOAEL for developmental toxicity was 1000 mg/kg/day and the NOAEL for teratogenicity was >=2000 mg/kg/day, which was the highest dose tested.  
OECD Guideline 414 (Prenatal Developmental Toxicity Study) - Inhalation - The NOAEC for developmental toxicity was >= 364 and the NOAEL for teratogenicity was >=364 ppm, which was the highest dose tested.  

Effect on developmental toxicity: via oral route

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Additional information

There are no available data on developmental toxicity for hydrocarbons, C13 -C20, n-alkanes, isoalkanes, cyclics, 40 -60% aromatics.However, there were several studies located for the structurally analogous test materials, JP-8 fuel and hydrodesulfurized kerosene. Thus read-across was performed.

In a developmental study (OECD TG 414), pregnant dams were dosed by oral gavage with 0, 500, 1000, 1500, or 2000 mg/kg of JP-8 during gestational days 6 through 15 (Cooper and Mattie, 1996). The NOAEL for fetotoxicity was 1000 mg/kg/day based on decreased body weight and the NOAEL for teratogenicity was >=2000 mg/kg/day, which was the highest dose tested. In another study, jet fuel A and kerosene were tested for developmental toxicity via inhalation exposure (Anonymous, 1979). For both substances, the NOAEL for developmental toxicity was >= 364 and the NOAEL for teratogenicity was >=364 ppm, which was the highest dose tested.

The following information is taken into account for any hazard / risk assessment:

OECD Guideline 414 (Prenatal Developmental Toxicity Study) - Oral Administration - The NOAEL for developmental toxicity was 1000 mg/kg/day and the NOAEL for teratogenicity was >=2000 mg/kg/day, which was the highest dose tested.

OECD Guideline 414 (Prenatal Developmental Toxicity Study) - Inhalation - The NOAEL for developmental toxicity was >= 1893 mg/m3 and the NOAEL for teratogenicity was >= 1893 mg/m3, which was the highest dose tested.

Justification for classification or non-classification

These findings do not warrant classification C13 -C20, n-alkanes, isoalkanes, cyclics, 40 -60% aromatics as a reproductive or developmental toxin under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.