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

Endpoint summary

Description of key information

Based on read-across using the analogue approach, hydrocarbons, C5-C6, n-alkanes, isoalkanes, < 5% n-hexane are not considered to be toxic after single exposure via the oral, dermal or inhalation route. However, based on the values of kinematic viscosity of hydrocarbon solvents, the test substance is considered an aspiration hazard, as it may cause lung damage if swallowed. Moreover, hydrocarbon solvents have the potential to cause anaesthetic effects at high concentrations.
Oral (OECD 401), rat: LD50 > 2000 mg/kg bw (read-across from n-pentane)
Oral (OECD 401), rat: LD50 > 16750 mg/kg bw (read-across from C-6 normal and iso paraffins (hexanes) and naphthenes (methyl-cyclohexane, dimethylcyclohexane), 25-35% n-hexane)
Inhalation (OECD 403), rat: LC50 > 23.2 mg/L (read-across from cyclopentane)
Inhalation (OECD 403), rat: LD50 = 259354 mg/m³ (read-across from C-6 normal and iso paraffins (hexanes) and naphthenes (methyl-cyclohexane, dimethylcyclohexane), 25-35% n-hexane)
Dermal (OECD 402), rabbits: LD50 > 3350 mg/kg bw (read-across from C-6 normal and iso paraffins (hexanes) and naphthenes (methyl-cyclohexane, dimethylcyclohexane), 25-35% n-hexane)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

There are no data available on acute 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 an acute oral toxicity study with n-pentane, 5 rats per sex were given a single oral dose of undiluted n-pentane at a dose of 2000 mg/kg (3.33 mL/kg) and were observed for 14 days (Frank, 1996). There were no mortalities or consistent signs of systemic toxicity through the 14 days observation period. No abnormalities noted at necropsy. The LD50 for n-pentane is thus greater than 2000 mg/kg bw.

In an acute oral toxicity study with test substance “C-6 normal and iso paraffins (hexanes) and naphthenes (methyl-cyclohexane, dimethylcyclohexane), 25-35% n-hexane”, 6 male rats were administered doses up to 25 mL/kg of the test substance by oral gavage, and observed for 14 days post-dosing (Hine and Zuidema, 1970). No mortality was observed at any of the doses. The oral LD50 is therefore greater than 16750 mg/kg bw (25 mL/kg; density of 0.67).

Acute inhalation toxicity studies were identified from n-pentane, cyclopentane and “C-6 normal and iso paraffins (hexanes) and naphthenes (methyl-cyclohexane, dimethylcyclohexane), 25-35% n-hexane”.

4 male rats per concentration were exposed by inhalation to n-pentane for 4 h (Frantik et al., 1994; no concentrations were reported). Animals were examined for neurotropic effects, specifically depression of seizure responses after exposure to an electrical impulse. Mortality was not reported and the LC50 was not calculated. The concentration resulting in 37% depression of the shortening of the tonic extension of hind limbs by 3 s in males was found to be 21000 ppm (6197 mg/m³).

Another acute inhalation study was identified for cyclopentane. In this study, 5 albino Sprague-Dawley rats/sex were administered 25.30 mg/L (nominal concentration of 26.40 mg/L) showed no observed mortalities after animals were exposed whole body for 4 hours (Jackson, 1983). Hunched posture was observed in all rats (male and female) during hours 1 to 4 of the exposure period. A few male rats exhibited reduction in bodyweight gain on the day following exposure. Subsequently though, bodyweight gain was similar to that observed in control rats. Food consumption was found to be slightly reduced in male rats for a single day while water consumption seemed unaffected following exposure to cyclopentane. One male rat also exhibited wet fur around the snout and jaws immediately following the exposure period. No macroscopic abnormalities were noted in rats exposed to cyclopentane and individual findings such as basophilic cortical tubules in kidneys, macrophage aggregates, alveolar hemorrhage and pneumonitis in the lungs were considered spontaneous in origin and not treatment-related. Lung to body-weight ratios were found to be within normal limits for all male and female rats. Based on the results discussed above, the 4-hour inhalation LC50 for cyclopentane is greater than 25.30 mg/L.

In an acute inhalation toxicity study, groups of 10 male rats were exposed to concentrations up to 81800 ppm of “C-6 normal and iso paraffins (hexanes) and naphthenes (methyl-cyclohexane, dimethylcyclohexane), 25-35% n-hexane” for 4 h (Hine and Zuidema, 1970). Animals were then observed for clinical signs and mortality for at least 6 days post-exposure. Several animals died during the exposure period. Surviving animals experienced severe toxicological effects during the exposure. One animal experienced convulsions during and after exposure and died on day 6 post-exposure. The LC50 was determined to be 73680 ppm (259354 mg/m³).

In an acute dermal toxicity study of the test substance, 5.0 mL/kg (corresponding to 3350 mg/kg bw) was placed on the shaved skin of 3 male rabbits (Hine and Zuidema, 1970). The test area was then covered with an occlusive dressing (saran wrap sleeve) for 4 h. After the exposure period, the test substance washed off, and the animals observed for toxicity and mortality over the next 14 days. No animals died; however, they did show signs of discomfort and uncoordinated movements after the exposure. The LD50 for dermal exposure is greater than 3350 mg/kg bw.

 

Based on evaluation of acute oral and inhalation toxicity data discussed above, hydrocarbons do not meet the criteria for classification as an acute oral or inhalation toxicant. Although there is only one acute studies identified for dermal exposure, physiochemical data suggests that absorption via the dermal route is not significant and that dermal toxicity is not a significant cause for concern. Additionally, it is generally assumed that exposure via the oral route leads to greater absorption of the substance compared with exposures via the dermal route. Oral exposure studies within the source substances did not report any potential for serious or severe toxicity by this route of exposure, therefore it is unlikely that toxicity via dermal exposure poses a significant risk.

 

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

 

Justification for selection of acute toxicity – oral endpoint
Based on the values of kinematic viscosity of hydrocarbon solvents, the test substance is considered an aspiration hazard, as it may cause lung damage if swallowed.

Justification for selection of acute toxicity – inhalation endpoint
For details please refer to section 7.9.1 of the technical dossier.

Justification for classification or non-classification

Based on read-across within an analogue approach, the available data on acute toxicity (oral, dermal and inhalation) 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.

However, based on the available data on physico-chemical properties (kinematic viscosity), hydrocarbon solvents meet the criteria for classification as aspiration hazard, Category 1 (H304) according to Regulation (EC) 1272/2008 and as Xn, R65 according to Directive 67/548/EEC.

Moreover, hydrocarbon solvents have the potential to cause anaesthetic effects at high concentrations. Based on the analogue approach, the available data on neurotoxicity meet the criteria for classification as STOT SE Cat. 3 (H336) according to Regulation (EC) 1272/2008 and as R67 according to Directive 67/548/EEC.