Hydrocarbons, C16-C22, n-alkanes, isoalkanes, <2% aromatics

Endpoint summary

Description of key information

Based on weight of evidence from studies on substances in the relevant carbon number range, the acute oral LD50 in male and female rats is considered to be >5000 mg/kg bw.
Based on an acute inhalation toxicity study performed with the substance itself, the acute (4-hour_ aerosol LC50 in male and female rats is considered to be >1 – 5 mg/l. However, the observed mortalities were concluded to be due to aspiration of the test material rather than indicating systemic toxicity. 
Based on weight of evidence from studies on substances in the relevant carbon number range, the acute dermal LD50 in male and female rats is considered to be >2000 mg/kg bw. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

No acute toxicity studies are available for the registration substance itself. However, Hydrocarbons, C16-C22, n-alkanes, isoalkanes, <2% aromatics has a carbon range covered by the carbon ranges of the analogue substances; Hydrocarbons, C18-C24, isoalkanes, <2% aromatics, GTL Kerosine, GTL Gasoil and GTL Base Oil Distillates for which reliable oral, inhalationand dermal toxicity data are available. Therefore read-across from the available studies with these substances is justified.

Oral

GTL Gasoil (C8-C26) was tested in an acute oral toxicity study according to the fixed dose method (OECD 420). Following a preliminary test in which there were no deaths at a dose level of 5000 mg/kg, an additional 4 fasted Sprague-Dawley rats received a dose of 5000 mg of the undiluted test material per kg body weight by gavage. There were no signs of toxicity, all animals showed normal gains in body weight, and there were no abnormalities on necropsy (SafePharm 2006a).

GTL Base Oil Distillates (C18-C50) was tested in an acute oral toxicity study according to the fixed dose method (OECD 420).Following a preliminary test in which there were no deaths at a dose level of 5000 mg/kg, an additional four fasted Sprague-Dawley DC rats received a dose of 5000 mg of the undiluted test material per kg body weight by gavage. There were no signs of toxicity, all animals showed normal gains in body weight, and there were no abnormalities on necropsy (Sanders, 2007). The acute oral LD₅₀ was therefore >5000 mg/kg bw.

Supporting data are also available for two grades of GTL Kerosine (C8-C16 and C8-C12) which were tested in acute oral toxicity studies according to OECD 420 and OECD 401, resulting in reported LD₅₀ values in excess of 5000 mg/kg (SafePharm, 2006b and Huntingdon Life Sciences 1997a).

Inhalation

 

An acute inhalation study has been performed with Hydrocarbons, C18-C24, isoalkanes, <2% aromatics in accordance with OECD Test Guideline 436 (Acute Toxic Class Method) and GLP (Griffiths, 2014). Two groups of six rats (three male, three female), were exposed for four hours to an aerosol atmosphere of the test substance (nose only) at mean measured test concentrations of 1.14 and 4.98 mg/l, followed by a 14-day observation period. 2/3 males and 1/3 females died following exposure to 4.98 mg/l, whereas no males and 1/3 females died at 1.14 mg/l. Common abnormalities noted during the study included increased respiratory rate, hunched posture, pilo-erection and wet fur; occasional instances of tip-toe gait were also noted. Surviving high dose animals recovered to appear normal on Day 8 post-exposure. Surviving low dose animals recovered to appear normal from Days 6 to 7 post-exposure.

 

In the high dose group, all animals exhibited body weight losses on Day 1 post-exposure. All surviving animals exhibited body weight losses or showed no body weight gain from Days 1 to 3 post-exposure, body weight gains were noted in all surviving animals during the remainder of the recovery period. In the low dose group, All males and two female animals exhibited body weight losses on Day 1 post-exposure. Body weight gains were noted in all surviving animals during the remainder of the recovery period.

 

Dark patches on the lungs were noted at necropsy amongst all three surviving animals from the high dose group and in one out of five surviving animals from the low dose group. A further surviving female from the low dose group exhibited a dark liver at the end of the fourteen day recovery period. Necropsy findings in animals that died during the course of the study included abnormally dark or dark patches on the lungs, dark livers and gaseous distension in the large intestine. Due to the observations noted, the study author considered that the deaths noted during the study may have been mainly attributable to local toxicity. Dark patches in the lungs and abnormally dark lungs in a proportion of animals in both treatment groups were associated with congestion at histopathological examination, and were considered to be treatment-related.

 

Additional histopathological examinations were performed on the lungs and trachea of all animals. Findings in the lungs animals that survived to the end of the study period were minimal to slight congestion, minimal to slight haemorrhage, moderate oedema, minimal to slight alveolar macrophaces, slight acute alveolar inflammation and minimal to slight acute perivascular inflammation. Findings in the trachea were limited to minimal intraepithelial inflammation. Examinations in animals that died during the study revealed effects on the lungs, namely slight to moderate congestion, slight haemorrhage, minimal to moderate oedema, minimal to slight alveolar macrophages minimal to slight alveolar inflammation and minimal to moderate acute perivascular inflammation. There were no findings in the trachea of decedent animals.

 

The histopathological findings are consistent with a conclusion that the observed mortalities were related to hydrocarbon aspiration-induced inflammation (i.e. chemical pneumonitis), rather than being indicative of systemic toxicity. The substance is therefore classified as Aspiration Toxicity Category 1.

Dermal

A study on the acute dermal toxicity of GTL Kerosine with a limited range, (C8-C12) reported an LD₅₀value of >2000 mg/kg bw for the test substance in rats (Huntingdon Life Sciences, 1997b). There were no deaths, no systemic toxicity or treatment related abnormalities at necropsy reported for the test substance. It is expected that based on lower bioavailabity of >C18 alkanes, acute toxicity by dermal route will be equal or less toxic than the lower molecular weight analogues.

In addition, relevant acute dermal toxicity studies with rats and rabbits are available for a number of related substances following administration by the dermal route, covering the higher carbon numbers in the range C20-C24. In all cases, the reported LD₅₀values are >2000 mg/kg bw.

Taking all available acute toxicity data for relevant carbon numbers into consideration it can be concluded that the acute oral and dermal LD₅₀values for Hydrocarbons, C16-C22, n-alkanes, isoalkanes, <2% aromatics are >5000 mg/kg bw and >2000 mg/kg bw, respectively.

Justification for classification or non-classification

On the basis of the available oral, inhalation and dermal data, Hydrocarbons, C16-C22, n-alkanes, isoalkanes, <2% aromatics does not require classification for lethal effects following a single exposure according to Regulation (EC) No. 1272/2008.

Since the substance is composed of aliphatic hydrocarbons and has low viscosity (kinematic viscosity: 2.4 mm²/s at 40°C), it may present an aspiration hazard in humans following oral exposure. This is supported by macroscopic and microscopic examinations performed following an acute inahaltion study with an aerosol atmosphere of the registered substance.It is therefore appropriate to classify the substance as Aspiration Toxicity Category 1 according to Regulation (EC) No. 1272/2008.