Dilithium azelate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

insufficient hazard data available (further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

insufficient hazard data available (further information necessary)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Value:

0.046 mg/cm²

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

5

AF for intraspecies differences:

5

Justification:

Standard worker assessment factor

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

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. REACH Annex V, Entry 9, groups fatty acids and their potassium, sodium, calcium and magnesium salts, including C6 to C24, predominantly even-numbered, unbranched, saturated or unsaturated aliphatic monocarboxylic acids. Since published reviews do not distinguish between the properties of monocarboxylic or dicarboxylic acids as a category, then the same interpretation can be applied to the dicarboxylic acids. Due to the close structural similarity and the narrow range of carbon chain numbers covered in this category, the toxicity expected to be similar across the category. 

 

None of the category substances have been tested by the inhalation route. 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 not in isolated form, so the potential for the generation of inhalable forms is low. Also, the use of the grease forms will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur.

 

Acute oral toxicity studies in rats conducted on lithium salts of dicarboxylic acids C6-C10 showed consistent evidence of acute toxicity, with a discriminating dose of 300 mg/kg bw. An acute dermal toxicity studies in rats conducted on dilithium adipate and dilithium sebacate, showed a lack of acute toxicity up to the highest dose tested (2000 mg/kg bw or greater). 

 

A combined short-term repeat dose and reproductive toxicity screening study via dermal route was conducted on fatty acids C18 -(unsaturated) lithium salts. No systemic effects were observed at the highest dose tested so the NOAEL was determined to be 1089.75 mg/kg bw/day. However, as there is no clear evidence of rate and level uptake of the substance to allow the potential for systemic toxicity, it is proposed not to use this study to calculate DNELs. Instead, it is proposed to conduct route to route extrapolation in order to calculate DNELs based results of the ongoing OECD 422 study via oral route on dilithium adipate. It is proposed that the acute/short-term DNEL is extrapolated from the long-term DNEL when available. ​

​

The experimental results from the repeated dose dermal toxicity study on fatty acids C18 (unsaturated) lithium did permit consideration of long-term local effects on the skin. The NOAEL for this effect was 111.25 mg/kg/day, which converts to 0.23 mg/cm²dilithium adipate based on lithium ion concentration and on the area of rat skin exposed in the subacute study (average weight of the rats in the study was 311 g, the body surface area was calculated as being approximately 9.1 x bw(g)0.66, and the approximate surface area exposed was 10%). 

 

Available data show that all the substances in the category of lithium salts of C6-C10 dicarboxylic acids exhibit a similar lack of irritant and corrosive properties requiring classification.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

insufficient hazard data available (further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

insufficient hazard data available (further information necessary)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.023 mg/cm²

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

10

AF for intraspecies differences:

10

Justification:

Standard general population assessment factor

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

insufficient hazard data available (further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

insufficient hazard data available (further information necessary)

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

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. REACH Annex V, Entry 9, groups fatty acids and their potassium, sodium, calcium and magnesium salts, including C6 to C24, predominantly even-numbered, unbranched, saturated or unsaturated aliphatic monocarboxylic acids. Since published reviews do not distinguish between the properties of monocarboxylic or dicarboxylic acids as a category, then the same interpretation can be applied to the dicarboxylic acids. Due to the close structural similarity and the narrow range of carbon chain numbers covered in this category, the repeated dose toxicity expected to be similar across the category.  

     

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 not in isolated form, so the potential for the generation of inhalable forms is low. The general population are only exposed to the substance as part of the formulated greases, which are viscous liquids. The use of the grease forms will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur.

 

Acute oral toxicity studies in rats conducted on lithium salts of dicarboxylic acids C6-C10 showed consistent evidence of acute toxicity, with a discriminating dose of 300 mg/kg bw. An acute dermal toxicity studies in rats conducted on dilithium adipate and dilithium sebacate, showed a lack of acute toxicity up to the highest dose tested (2000 mg/kg bw or greater). 

 

A combined short-term repeat dose and reproductive toxicity screening study via dermal route was conducted on fatty acids C18 -(unsaturated) lithium salts. No systemic effects were observed at the highest dose tested so the NOAEL was determined to be 1089.75 mg/kg bw/day. However, as there is no clear evidence of rate and level uptake of the substance to allow the potential for systemic toxicity, it is proposed not to use this study to calculate DNELs. Instead, it is proposed to conduct route to route extrapolation in order to calculate DNELs based results of the ongoing OECD 422 study via oral route on dilithium adipate. It is proposed that the acute/short-term DNEL is extrapolated from the long-term DNEL when available. ​

​

The experimental results from the repeated dose dermal toxicity study on fatty acids C18 (unsaturated) lithium did permit consideration of long-term local effects on the skin. The NOAEL for this effect was 111.25 mg/kg/day, which converts to 0.23 mg/cm² dilithium adipate based on lithium ion concentration and on the area of rat skin exposed in the subacute study (average weight of the rats in the study was 311 g, the body surface area was calculated as being approximately 9.1 x bw(g)0.66, and the approximate surface area exposed was 10%). 

 

Available data show that all the substances in the category of lithium salts of C6-C10 dicarboxylic acids exhibit a similar lack of irritant and corrosive properties requiring classification.