Hydrocarbons, C5-C7, n-alkanes, isoalkanes, < 5% n-hexane

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no adverse effect observed

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

There are no data available on effects on fertility of hydrocarbons, C5-C6, n-alkanes, isoalkanes, < 5% n-hexane. However, there are reliable data available considered suitable for read-across using the analogue approach.The target substance is a hydrocarbon solvent with carbon numbers in the range of C5 to C6. The main constituents of the mixed solvent consist of about 43% of C6 species and about 57% of C5 species. n-Hexane is only present in concentrations < 5% of the total volume.The source substances chosen for read-across have similar toxicological properties as the target substance. There is only one distinguishing characteristic for n-hexane. n-Hexane has unique toxicological properties due to its ability to be metabolized to the neurotoxic metabolite 2,5-hexanedione. Other C6 species will not be metabolized to 2,5-hexanedione. For this reason, n-hexane and hydrocarbon solvents containing n-hexane at levels greater than 5% represent a worst case scenario.

Taking into account all available data, animal and human toxicity data as well as environmental fate and effects data show that source substances have similar (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 two-generation reproduction toxicity study conducted similar to OECD 416, commercial hexane (52% n-hexane) was administered to groups of 25 mal and 25 female rats at nominal concentrations of 900, 3000, or 9000 ppm for 10 weeks pre-breeding, 3 weeks during breeding and postnatal days 4 -28 (Daughtrey et al., 1994). After weaning, pups were selected to be parents for the F2 generations, and treated similarly to their parents, except their pre-breeding exposure was 8 weeks. During exposure, animals were monitored for mortality, clinical signs, food consumption, and body weight. Offspring were examined for body weight, survival, and viability. Both parents and offspring were sacrificed and examined for gross abnormalities, and in the case of adults histopathology was also performed.

Reproductive parameters were similar in exposure and control groups. There was reduced body weight in the F1 and F2 generation in both sexes in the 9000 ppm exposure group in both adults and offspring. The NOAEC for systemic effects is therefore 3000 ppm (corresponding to 10560 mg/m³). Since there were no adverse effects in offspring without adverse maternal effects, the NOAEC for reproductive toxicity is ≥ 9000 ppm (corresponding to 31680 mg/m³).

Furthermore, no adverse effects on reproductive organs and tissues were observed in subchronic and chronic toxicity studies when commercial hexane or n-pentane were given by inhalation to rats and mice of both sexes.

Taking into account all available data, hydrocarbons, C5–C6, n-alkanes, isoalkanes, < 5% n-hexane are not considered be toxic to reproduction.

Short description of key information:
Based on read-across using the analogue approach, hydrocarbons, C5-C6, n-alkanes, isoalkanes, < 5% n-hexane are not considered be toxic to reproduction.
Inhalation (similar to OECD 416), rat: NOAEC for reproductive toxicity ≥ 31680 mg/m³ (read-across from commercial hexane)
Inhalation (similar to OECD 416), rat: NOAEC for systemic effects = 10560 mg/m³ (read-across from commercial hexane)

Effects on developmental toxicity

Description of key information

Based on read-across using the analogue approach, hydrocarbons C5-C6, n-alkanes, isoalkanes, < 5% n-hexane are not expected to have a potential to induce developmental toxicity.
Oral (according to OECD 414), rat: NOAEL for maternal and developmental toxicity ≥ 1000 mg/kg bw/day (read-across from n-pentane)
Inhalation (similar to OECD 414), mouse: NOAEC for maternal toxicity = 3168 mg/m³ (read-across from commercial hexane)
Inhalation (similar to OECD 414), mouse: NOAEC for developmental toxicity = 10560 mg/m³ (read-across from commercial hexane)
Inhalation (similar to OECD 414), rat: NOAEC for maternal toxicity = 10560 mg/m³ (read-across from commercial hexane)
Inhalation (similar to OECD 414), rat: NOAEC for developmental toxicity ≥ 31680 mg/m³ (read-across from commercial hexane)

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

adverse effect observed

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

There are no data available on effects on developmental toxicity of hydrocarbons, C5-C6, n-alkanes, isoalkanes, < 5% n-hexane. However, there are reliable data available considered suitable for read-across using the analogue approach.The target substance is a hydrocarbon solvent with carbon numbers in the range of C5 to C6. The main constituents of the mixed solvent consist of about 43% of C6 species and about 57% of C5 species. n-Hexane is only present in concentrations < 5% of the total volume.The source substances chosen for read-across have similar toxicological properties as the target substance. There is only one distinguishing characteristic for n-hexane. n-Hexane has unique toxicological properties due to its ability to be metabolized to the neurotoxic metabolite 2,5-hexanedione. Other C6 species will not be metabolized to 2,5-hexanedione. For this reason, n-hexane and hydrocarbon solvents containing n-hexane at levels greater than 5% represent a worst case scenario.Taking into account all available data, animal and human toxicity data as well as environmental fate and effects data show that source substances have similar (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 developmental toxicity study according to OECD 414, n-pentane was orally administered via gavage to 25 rats per dose at dose levels of 100, 500 and 1000 mg/kg bw/day from days 6 through 15 of gestation (Trimmer, 1997). There were no signs of maternal toxicity at any dose level. There were no treatment-related changes in mean body weight, body weight gain, uterine weight, corrected body weight, food consumption, or uterine implantation data. No treatment-related mortalities or clinical signs of toxicity were observed. The NOAEL for maternal toxicity is therefore ≥ 1000 mg/kg bw/day.

There were no signs of developmental toxicity at any dose level and no treatment-related changes in growth or increased fetal death. Moreover, no changes in total malformations or variations were found. Thus, the NOAEL for developmental toxicity is ≥ 1000 mg/kg/day.

In a developmental toxicity study conducted similar to OECD 414, groups of 30 pregnant mice were exposed to commercial hexane (52.19% n-hexane) at concentrations of 900, 3000 and 9000 ppm for 6 h/day during gestational days 6-15 (API, 1989). The animals were then sacrificed on gestation day 18. During the study, the animals were examined for clinical signs, mortality, food and water consumption, and body weights taken. After sacrifice, the internal organs were examined, and the uterus was examined for viable fetuses, number of resorptions, and number of corpora lutea. Fetuses were examined for malformations. Necropsy revealed color changes in the lungs of females in the 3000 and 9000 ppm groups. Fetuses from dams in the 9000 ppm group had a statistically significant increase in some skeletal abnormalities. The maternal NOAEC in mice was 900 ppm (corresponding to 3168 mg/m³) based on lung color changes. The developmental NOAEC in mice was 3000 ppm (corresponding to 10560 mg/m³) based on skeletal abnormalities.

In another developmental toxicity study conducted similar to OECD 414, 25 pregnant rats were exposed to commercial hexane (52.19% n-hexane) at concentrations of 900, 3000 and 9000 ppm for 6 h/day during gestational days 6-15 (API, 1989). The animals were then sacrificed on gestation day 21. During the study, the animals were examined for clinical signs, mortality, food and water consumption, and body weights taken. After sacrifice, the internal organs were examined, and the uterus was examined for viable fetuses, number of resorptions, and number of corpora lutea. Fetuses were examined for malformations. Necropsy revealed color changes in the lungs of females in the 9000 ppm groups along with reduced body weight gain, and reduced food consumption. No treatment related abnormalities was seen in the fetuses. The maternal NOAEC in rats is 3000 ppm (corresponding to 10560 mg/m³) based on lung color changes, reduced body weight gain, and reduced food consumption. The developmental NOAEC in rats is ≥ 9000 ppm (corresponding to 31680 mg/m³).

Taking into account all available data, hydrocarbons, C5–C6, n-alkanes, isoalkanes, < 5% n-hexane 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.