Dilithium azelate

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available (further information necessary)

Quality of whole database:

A combined repeat dose and reproductive and developmental screening study (OECD 422) is currently being conducted on dilithium adipate and a 90-day repeat dose toxicity study via oral route is proposed for dilithium sebacate.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

The lithium salts of dicarboxylic salts C6 - C10 have vapour pressures of <1.3 x 10(-8) Pa at 20°C and are exclusively manufactured in situ in base oil and the use of the grease forms will not result in aerosols, particles or droplets of an inhalable size.

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

The lithium salts of dicarboxylic salts C6 - C10 have vapour pressures of <1.3 x 10(-8) Pa at 20°C and are exclusively manufactured in situ in base oil and the use of the grease forms will not result in aerosols, particles or droplets of an inhalable size.

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

298.5 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

A key 28-day toxicity and reproductive toxicity screen, using the OECD 422 study design, was conducted in rats on monocarboxylate fatty acids C18 (unsaturated) lithium salts via dermal administration. This substance is a structural analogue by virtue of its chemical structure and therefore data have been read across from fatty acids C18 (unsaturated) lithium salts to members of the dilithium salts of dicarboxylic acids C6-10 category.

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

0.23 mg/cm²

Study duration:

subacute

Species:

rat

Quality of whole database:

A key 28-day toxicity and reproductive toxicity screen, using the OECD 422 study design, was conducted in rats on monocarboxylate fatty acids C18 (unsaturated) lithium salts via dermal administration. This substance is a structural analogue by virtue of its chemical structure and therefore data have been read across from fatty acids C18 (unsaturated) lithium salts to members of the dilithium salts of dicarboxylic acids C6-10 category.

Additional information

The substances in the category are considered to be similar on the basis that they have common structures of a lithium ion varying only by the length of the fatty acid chain. As a result, it is expected that the substances will have similar, predictable properties. Due to the close structural similarity and the narrow range of carbon chain numbers covered in this category, the repeated dose toxicity potential is expected to be similar across the category. 

 

A key 28-day toxicity and reproductive toxicity screen, using the OECD 422 study design, was conducted in rats on monocarboxylate fatty acids C18 (unsaturated) lithium salts via dermal administration. Although this substance is not in the category, it is a structural analogue by virtue of its chemical structure and therefore read across from data on fatty acids C18 (unsaturated) lithium salts to members of the dilithium salts of dicarboxylic acids C6-10 category is considered to be justified – see read across justification.

 

The test material was administered at dose levels of 0, 100, 300 and 1000 mg/kg bw/day nominal, equating to 111.25, 345 and 1089.75 mg/kg bw/day by analysis, and were based on local dermal effects from a dose range finding study. There was a 2-week post-dose observation period for satellite high dose level and control groups. No systemic toxicity directly related to the administration of the substance was observed, although dose-related local effects were seen in the skin of treated animals in the 300 and 1000 mg/kg bw/day groups. Since the highest dose of 1089.75 mg/kg bw/day was essentially equivalent to a ‘limit dose’ and was considered to be the systemic NOAEL, this lithium fatty acid salt is not considered to be systemically hazardous. A local NOAEL of 111.25 mg/kg bw/day was determined due to dermal changes seen at higher concentrations.

 

A number of supporting subacute or subchronic toxicity studies by oral or dermal administration on greases containing ca 8.8% lithium 12 -hydroxystearate and 1.8% dilithium azelate in base oil have been published. These studies gave NOAEL levels of 2100 mg/kg bw/day of the grease. However, it should be noted that these greases also contained other additives and full experimental and analytical details were not presented. Therefore, they can only provide an indication of potential toxicity rather than definitive NOAELs for the category of lithium dicarboxylic acid salts. Nevertheless, the results confirm the low toxicity potential for these substances. 

 

The results from this study also permitted consideration of long-term local effects on the skin. The NOAEL for this effect was 111.25 mg/kg/day, which converts to 0.86 mg/cm²based on the area of rat skin exposed in the subacute study (average weight of the rats in the study was 311g, the body surface area was calculated as being approximately 9.1 x bw(g)0.66, and the approximate surface area exposed was 10%).

 

Assuming a molecular weight of 288.4 g/mol for fatty acids C18-(unsaturated) lithium salt with a lithium content of 2.4% and a molecular weight of 158 g/mol for dilithium adipate with a lithium content of 8.8%, the values for fatty acid C18-(unsaturated) lithium salts have been recalculated for dilithium adipate, as the smallest substance in the category.

 

The systemic NOAEL of 1089.75 mg/kg bw/day is equivalent to 26.2 mg Li/kg bw/day and thus 298.5 mg/kg bw/day dilithium adipate. The local NOAEL of 111.25 mg/kg bw/day is equivalent to 2.68 mg Li/kg bw/day and thus 30.5 mg/kg bw/day dilithium adipate. The NOAEL for local long-term effects on the skin of 0.86 mg/cm² is equivalent to 0.021 mg Li/cm² and thus 0.23 mg/cm² dilithium adipate.

 

On the basis of the lack of systemic toxicity read across from relevant structural analogue (fatty acids C18 (unsaturated) lithium salts - see read across justification document), no classification for specific target organ toxicity is required for dilithium salts of dicarboxylic acids C6 -C10.

 

Further testing is proposed or currently ongoing to support this conclusion. A combined repeat dose and reproductive and developmental screening study (OECD 422) is currently being conducted on dilithium adipate and a 90-day repeat dose toxicity study via oral route is proposed for dilithium sebacate.

Justification for classification or non-classification

Not classified for STOT systemic. No toxicologically significant adverse effects observed.