Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

Overall, on the basis of the category justification for the C14 to C22 fatty acid lithium salts, and supporting evidence, the lack of reproductive and developmental toxicity when C18 (unsaturated) lithium salts was administered to rats can be read across to other members of the category. A dermal reprotoxicity screening study in rats conducted according to OECD 422 showed no adverse effect was seen in any of the reproductive parameters examined at any dose. The NOAEL for reproductive and developmental toxicity is 1089.75 mg/kg/day.

OECD 422 combined repeat dose and reproductive toxicity screening studies via oral route are currently being conducted on lithium myristate (C14), fatty acids C16 -18 lithium salts, lithium 12 -hydroxystearate (C18 -OH) and fatty acids C16 -18 (even numbered) saturated and C16 -20 (even numbered) unsaturated lithium salts. The dossier will be updated when the results of these studies are available.

Effect on fertility: via oral route
Endpoint conclusion:
no study available (further information necessary)
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 089.75 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
GLP study conducted according to standard guideline
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 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 reproductive toxicity is expected to be similar across the category. Although fatty acids C18 (unsaturated) lithium salts is not in the list of substances being registered, this substance falls within the definition of the lithium salts of fatty acids C14-C22 category by virtue of its chemical structure and therefore read across from data on fatty acids C18 (unsaturated) lithium salts to other members of the category is considered to be justified (see category and read across justification).

A key toxicity and reproductive toxicity screen, using the OECD 422 study design, was conducted in rats on fatty acids C18 (unsaturated) lithium salts via dermal administration. The test material was administered at dose levels of 0, 100, 300 and 1000 mg/kg/day nominal, equating to 111.25, 345 and 1089.75 mg/kg/day by analysis, and were based on local dermal effects from a dose range finding study. There were no treatment-related effects at any dose level on any of the reproductive parameters evaluated in this study, or in any of the developmental parameters evaluated. Based on these data, the NOAEL for reproductive and developmental toxicity was 1089.75 mg/kg/day.

Further testing

OECD 422 combined repeat dose and reproductive toxicity screening studies via oral route are currently being conducted on lithium myristate (C14), fatty acids C16 -18 lithium salts, lithium 12 -hydroxystearate (C18 -OH) and fatty acids C16 -18 (even numbered) saturated and C16 -20 (even numbered) unsaturated lithium salts. The dossier will be updated when the results of these studies are available.

Effects on developmental toxicity

Description of key information

Overall, on the basis of the category justification for the C14 to C22 fatty acid lithium salts, the lack of developmental toxicity when C18 (unsaturated) lithium salts and grease containing lithium 12-hydroxystearate were administered to rats can be read across to other members of the category, and no classification for this endpoint is required. A dermal reprotoxicity screening study in rats conducted according to OECD 422 in which no adverse effect was seen in any of the reproductive/developmental parameters examined at any dose. Based on these data, the dermal NOAEL for reproductive and developmental toxicity was 1089.75 mg/kg/day.

Further testing

OECD 422 combined repeat dose and reproductive toxicity screening studies via oral route are currently being conducted on lithium myristate (C14), fatty acids C16 -18 lithium salts, lithium 12 -hydroxystearate (C18 -OH) and fatty acids C16 -18 (even numbered) saturated and C16 -20 (even numbered) unsaturated lithium salts. The dossier will be updated when the results of these studies are available.

A testing proposal for a pre-natal development toxicity study via oral route, as required under Annex IX of REACH, has been included for lithium 12 -hydroxystearate and the results will be read across to fatty acids C16 -18 lithium salts, though the testing proposal will be confirmed after the completion of the OECD 422 studies via oral route.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available (further information necessary)
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 089.75 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
GLP study conducted according to standard guideline
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 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 developmental toxicity is expected to be similar across the category. Although fatty acids C18 (unsaturated) lithium salts is not in the list of substances being registered, this substance falls within the definition of the lithium salts of fatty acids C14-C22 category by virtue of its chemical structure and therefore read across from data on fatty acids C18 (unsaturated) lithium salts to other members of the category is considered to be justified (see category and read across justification).

A key toxicity and reproductive toxicity screen, using the OECD 422 study design, was conducted in rats on fatty acids C18 (unsaturated) lithium salts via dermal administration. The test material was administered at dose levels of 0, 100, 300 and 1000 mg/kg/day nominal, equating to 111.25, 345 and 1089.75 mg/kg/day by analysis, and were based on local dermal effects from a dose range finding study. There were no treatment-related effects at any dose level on any of the reproductive parameters evaluated in this study, or in any of the developmental parameters evaluated. Based on these data, the NOAEL for reproductive and developmental toxicity was 1089.75 mg/kg/day.

Lithium 12-hydroxystearate

A supporting dermal developmental toxicity study in rats using a grease containing ca. 8% lithium 12-hydroxystearate in base oil, together with additives, is reported. This showed no adverse reproductive or developmental effects. The NOAEL (developmental) was 2000 mg/kg bw/day, and the NOAEL (maternal) was 500 mg/kg bw/day of the grease (160 and 40 mg/kg bw/day of lithium 12-hydroxystearate respectively).

Further testing

OECD 422 combined repeat dose and reproductive toxicity screening studies via oral route are currently being conducted on lithium myristate (C14), fatty acids C16 -18 lithium salts, lithium 12 -hydroxystearate (C18 -OH) and fatty acids C16 -18 (even numbered) saturated and C16 -20 (even numbered) unsaturated lithium salts. The dossier will be updated when the results of these studies are available.

A testing proposal for a pre-natal developmental toxicity study via oral route, as required under Annex IX of REACH, has been included for lithium 12 -hydroxystearate and the results will be read across to fatty acids C16 -18 lithium salts, though the testing proposal will be confirmed after the completion of the OECD 422 studies via oral route.

Justification for classification or non-classification

Not classified. No adverse reproductive or developmental toxicity effects observed.

Additional information