Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Value:
3 mg/m³
DNEL related information
DNEL derivation method:
other: General nuisance dust OEL for chronic exposure to inert alveolar (respirable) dust used as DNEL surrogate in accordance with ECHA REACH TGD R.8
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Value:
6 mg/m³
DNEL related information
DNEL derivation method:
other: General nuisance dust OEL for acute exposure to inert alveolar (respirable) dust used as DNEL surrogate in accordance with ECHA REACH TGD R.8

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:
DNEL (Derived No Effect Level)
Value:
0.172 mg/cm²
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
AF for intraspecies differences:
5
Justification:
Standard worker intraspecies assessment factor (AF 5) applied
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 and the presence of unsaturated and/or hydroxyl functional groups. 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 is expected to be similar across the category.

Inhalation

The category members are almost exclusively produced and used directly in grease form. They have vapour pressures of less than 10 E-10 Pa and melting points of greater than 160°C, 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. Only two category substances – Fatty acids C16-18, lithium salts and lithium 12-hydroxystearate – are produced to some extent in solid form and then subsequently formulated by occupational downstream users into a grease form. From the granulometry data on the solid, generation of dusts of an inhalable size cannot be excluded. However, at the production and occupational downstream user sites, the formation of dusts/aerosols is not significant due to specific operational conditions and implemented general dust RMMs. None of the category substances have been tested by the inhalation route. However, a number of acute oral and dermal toxicity studies in rats conducted on lithium salts of myristic (C14),12-hydroxystearic (C18 hydroxylated), stearic (C18), C18 unsaturated and behenic (C22) monocarboxylic acids showed consistent evidence of a lack of acute toxicity up to the highest doses tested (2000 mg/kg or greater). This value is well above the cut off values for classification for acute toxicity hazard of dusts. This value is considerably higher than the general dust limits, which apply in any case.  Although no substance specific intrinsic inhalative toxicity is expected, generally accepted OELs derived for inert (nuisance) dust/particulates not otherwise classified (PNOCs) of 10 mg/m³ for chronic and 20 mg/m³ for acute exposure to inhalable dust and of 3 mg/m³ for chronic and of 6 mg/m³ for acute exposure to alveolar (respirable) dust are applicable and must be adhered to, to avoid non-specific inhalative dust toxicity. By adherence to the general dust limits, the risk to humans can be considered to be sufficiently controlled. In accordance with ECHA REACH TGD R.8, the general dust limits are used as DNEL surrogate.

Dermal

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 studies via oral route on lithium myristate, lithium 12 -hydroxystearate, fatty acids C16 -18 lithium salts, and fatty acids C16 -18 (even numbered) saturated and C16 -20 (even numbered) unsaturated lithium salts. 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 permits 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/cm2 based 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%). Using a standard worker assessment factor of 5, the DNEL was calculated to be 0.172 mg/cm2.

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:
0.086 mg/cm²
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
AF for intraspecies differences:
10
Justification:
Standard general population intraspecies assessment factor (AF 10) applied
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:
no hazard identified
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 and the presence of unsaturated and/or hydroxyl functional groups. 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 is expected to be similar across the category.

Inhalation

The category members are almost exclusively produced and used directly in grease form. They have vapour pressures of less than 10 E-10 Pa and melting points of greater than 160°C, 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. Only two category substances – Fatty acids C16-18, lithium salts and lithium 12-hydroxystearate – are produced to some extent in solid form and then subsequently formulated by occupational downstream users into a grease form. From the granulometry data on the solid, generation of dusts of an inhalable size cannot be excluded. However, at the production and occupational downstream user sites, the formation of dusts/aerosols is not significant due to specific operational conditions and implemented general dust RMMs. None of the category substances have been tested by the inhalation route. However, a number of acute oral and dermal toxicity studies in rats conducted on lithium salts of myristic (C14),12-hydroxystearic (C18 hydroxylated), stearic (C18), C18 unsaturated and behenic (C22) monocarboxylic acids showed consistent evidence of a lack of acute toxicity up to the highest doses tested (2000 mg/kg or greater). This value is well above the cut off values for classification for acute toxicity hazard of dusts. This value is considerably higher than the general dust limits, which apply in any case. Although no substance specific intrinsic inhalative toxicity is expected, generally accepted OELs derived for inert (nuisance) dust/particulates not otherwise classified (PNOCs) of 10 mg/m³ for chronic and 20 mg/m³ for acute exposure to inhalable dust and of 3 mg/m³ for chronic and of 6 mg/m³ for acute exposure to alveolar (respirable) dust are applicable and must be adhered to, to avoid non-specific inhalative dust toxicity. By adherence to the general dust limits, the risk to humans can be considered to be sufficiently controlled. In accordance with ECHA REACH TGD R.8, the general dust limits are used as DNEL surrogate.

Dermal

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 studies via oral route on lithium myristate, lithium 12 -hydroxystearate, fatty acids C16 -18 lithium salts, and fatty acids C16 -18 (even numbered) saturated and C16 -20 (even numbered) unsaturated lithium salts. 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 toxicity study on fatty acids C18 (unsaturated) lithium permits 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/cm­2 based 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%).

Oral

Combined short-term repeat dose and reproductive toxicity studies via oral route are currently ongoing for lithium myristate, fatty acids C16 -18 lithium salts, lithium 12 -hydroxystearate and fatty acids C16 -18 (even numbered) saturated and C16 -20 (even numbered) unsaturated lithium salts. The dossier will be updated with the results of these studies once available. Testing proposals for a 90 day repeat dose toxicity study and a pre-natal developmental toxicity study on lithium 12 -hydroxystearate have also been submitted, pending the outcome of the ongoing OECD 422 studies, and the dossiers will be further updated with these results, when available.