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Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Study duration:
subacute
Species:
rat
Additional information

There are no data available on toxicity to reproduction 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).

In a reproduction/developmental toxicity screening test, males and female rats were given orally by gavage 100, 300 and 1000 mg/kg undecane (C11) per day (Ministry of Health and Welfare, Japan, 1996). Male rats were dosed for 46 days (14 days prior to mating and then during the mating period) and female rat from 14 days before mating to day 3 of lactation similar to OECD 421.

Salivation was observed in males and females given 300 and 1000 mg/kg of the test substance. Body weight gain was suppressed in males given 1000 mg/kg, and body weights were increased in females given 1000 mg/kg during the lactation period. Food consumption was decreased in males given 300 and 1000 mg/kg in the first half of the administration period, increased in males given 1000 mg/kg in the second half of the administration period, and increased in females given 1000 mg/kg in the second half of pregnancy and during the lactation period. Hematological and blood chemical examinations revealed a decrease in hemoglobin concentration, an increase in the white blood cell count, a decrease in albumin, and increases in alpha 2µ-globulin, GPT, cholinesterase and total cholesterol in males given 1000 mg/kg. Relative liver weights and absolute and relative thymus weights were increased in males given 1000 mg/kg, and absolute and relative liver weights were elevated in females given 1000 mg/kg. No effects were detected in the autopsy or histopathology findings. Due to the lack of effects in both sexes and the lack of corresponding histopathology, these effects are determined not to be toxicologically relevant. The NOAEL for repeated dose toxicity is considered to be ≥ 1000 mg/kg/day for both sexes.

No treatment-related effects were observed on the sex cycle of females and copulation and conception of males and females. In addition, no dose-related effects were observed on the weights of reproductive organs (testis, epididymis and ovary) and there were no abnormalities noted in the dissection and histopathological examination. Incidentally, the reproductive organs of infertile cases showed no histopathological findings suggesting the causes. Abnormal cases observed in this study were confirmed to be spontaneous when compared to historical controls. Those cases observed in the present study were considered to be unrelated to the test substance. The number of live or dead pups delivered per each dam in the test groups showed no apparent difference from that in the control group if those dead and unknown pups in those cases of abnormal delivery or death of all of the litter during nursing were excluded. The body weight gain rates of both males and females in the 1000 mg/kg bw group were observed to be reduced, but no treatment-related effects were observed as a result of general condition observation or dissection. The NOAEL for reproductive performance was considered to be ≥ 1000 mg/kg bw/day.

Furthermore, no adverse effects on reproductive organs were observed in several 90-day studies when hydrocarbons were given by the oral (C11-C14; C10-C13), inhalation (C11-C14; C10-C12) or dermal (hydrodesulfurized kerosene) route to male and female rats.

In addition, a testing proposal for a “Two Generation Reproductive Toxicity Test”has been proposed with a C9-C20 aliphatic hydrocarbon solvent, as a test substance with a wide range of hydrocarbon fluids. The results will be read-across to Distillates (Fischer-Tropsch), 210-360 degree Celsius, hydrotreated, isoalkanes, cyclics, <0.1% aromatics based on an analogue approach as permitted according to Regulation (EC) 1907/2006, Annex XI. Based on the outcome of the two generation reproductive toxicity study, the next steps in the testing strategy will be reconsidered. In accordance with Regulation (EC) 1907/2006, which specifies that unnecessary tests should be avoided in terms of animal welfare, it is suggested to conduct the proposed two generation reproductive toxicity study with C9-C20 aliphatic hydrocarbon solvent as a representative test substance.


Short 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 be toxic to reproduction.
Reproduction/Developmental Toxicity Screening Test (OECD TG 421), oral, rat: NOAEL for developmental toxicity and reproductive toxicity ≥ 1000 mg/kg/day.

Effects on developmental toxicity

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 expected to have a potential to induce developmental toxicity.
Prenatal Developmental Toxicity Study (OECD TG 414), oral, rat: NOAEL for developmental toxicity ≥ 1000 mg/kg bw/day
Prenatal Developmental Toxicity Study (OECD TG 414), inhalation, rat: NOAEC for developmental toxicity ≥ 5220 mg/m3
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
5 220 mg/m³
Study duration:
subacute
Species:
rat
Additional information

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).

Hydrocarbons, C16-C20 n-alkanes, isoalkanes, cyclics, < 2% aromatics were administered by oral gavage to three groups of Crl:CDBR female rats at doses of 400, 800, and 1000 mg/kg/day according to OECD 414 (ExxonMobil, 1996). A fourth group (Group 1) served as a control and received the carrier (corn oil) only. Mated females were dosed once daily from Gestation Day (GD) 6 through GD 15. Dosing volumes were 5 mL/kg for all groups and based on the animals' most recent body weights.

There was no evidence of overt systemic maternal toxicity at any dose level tested. Overt signs of maternal toxicity were not apparent at any dose tested, as indicated by the absence of adverse clinical or postmortem findings or effects on body weight, food consumption, and/or uterine implantation data. Similarly, there were no treatment-related adverse effects on fetal development or growth observed at any dose level tested. There was a statistically significant increase in the incidence of rudimentary ribs in the low dose (400 mg/kg/day) group, but not at the higher doses, compared with controls, which resulted in an increased incidence of total fetuses with skeletal variations in the 400 mg/kg/day group. However, all these incidences were within the historical control range of this laboratory. Therefore, this common finding in fetal rats was not considered biologically important. Accordingly, the NOAEL for the maternal and developmental toxicity was determined to be ≥ 1000 mg/kg/day under the conditions of this study.

Hydrocarbons, C10-C12, isoalkanes, < 2% aromatics were administered to pregnant female rats by inhalation exposure to vapor concentrations of 300 or 900 ppm, 6 hours/day during gestation days 6 to 15 to assess developmental toxicity similar to OECD 414 (ExxonMobil, 1978).  Included in this study was a negative control (chamber exposed) group and a positive control group that was treated via gastric intubation on gestational days 6-15 with 400mg/kg/day of acetylsalicylic acid.  All surviving females were sacrificed on Day 21 of testation and fetuses examined for external, soft tissue and skeletal malformations.  Pregnancy rate, mortality, body weight gain and gross postmortem observations were unaffected by treatment.  The treatment at either dose level had no effect on reproductive endpoints, fetal size, sex distribution, ossification variation, or fetal examination endpoints. Thus, there was no evidence of maternal or fetal toxicity at either exposure level tested.  Based on these results, the NOAEL for maternal and developmental toxicity were greater than or equal to 900 ppm (≥ 5220 mg/m3).

In conclusion, based on read-across using the analogue approach, Distillates (Fischer-Tropsch), 210-360 degree Celsius, hydrotreated, isoalkanes, cyclics, <0.1% aromatics are not expected to have a potential to induce developmental toxicity.

Justification for classification or non-classification

Based on the read-across within an analogue approach, the available data on toxicity to reproduction 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.


Additional information