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Description of key information

No repeated dose toxicity study with zinc neodecanoate basic is available, thus the repeated dose toxicity will be addressed with existing data on the individual assessment entities zinc and neodecanoate.

In relevant and reliable repeated dose toxicity studies as well as supporting studies for both assessment entities of zinc neodecanoate basic, there were no toxicological findings reported that would justify a classification for specific target organ toxicity - repeated exposure, oral.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Zinc

From studies in which humans were supplemented with zinc (as zinc gluconate) it was concluded that women are more sensitive to the effects of high zinc intake and that a dose of 50 mg Zn/day is the human NOAEL. This corresponds to a daily exposure of 0.83 mg Zn/kg bw. At the LOAEL of 150 mg Zn/day, clinical signs and indications for disturbance of copper homeostasis have been observed. Studies conducted on animals are not discussed here, since information on human experience are considered of higher relevance for hazard assessment purposes and should take precedence over animal studies. For further information on the toxicity of zinc, please refer to the relevant sections in the IUCLID and CSR.

Neodecanoate

Repeated dose toxicity, oral:

Seven male and seven female rats were exposed to 0; 10; 30; 100, or 300 mg/kg/day propanoic acid, 2,2-dimethyl- (CAS# 75-98-9) by oral gavage for 28 consecutive days (Shell Research Ltd., 1990). No treatment related changes were observed in body weight, food intake, haematology, or histopathology. The only clinical signs seen in this study were a shaking of heads, sneezing, dark nasal discharge, immediately after dosing 100 and 300 mg/kg/day. This behaviour could result from a mild irritant effect of the volatile acidic test compound. Slight increase of alkaline phosphatise, cholesterol and bilirubin levels at the 100 and 300 mg/kg/day dose levels, and slight increase of alkaline phosphatise and cholesterol levels in the plasma of females at the 30 mg/kg/day dose level. Increase in kidney and liver weight was observed in the 300 mg/kg/day group. None of these changes correlated with histopathological effects. These findings were considered adaptive changes and not indicative of a treatment-related adverse effect. The no observed adverse effect level (NOAEL) in this study was 300 mg/kg.

 

Five male and five female rats were exposed to 0; 10; 55; or 300 mg/kg/day fatty acids, C9-C13 neo (CAS# 68938-07-8) by oral gavage for 28 consecutive days (Shell Internationale Petroleum Maatschappij, 1994). There were no mortalities. Increased salivation was observed after dosing in rats receiving 300 mg/kg. No treatment related changes were observed in body weight, food consumption, haematology, or clinical chemistry. In males receiving 300 mg/kg, kidney weight increased and necropsy revealed an abnormal appearance of the kidney. A dose-related hyaline droplet was noted in males at all treatment levels. The findings in the kidney of the treated males are species and sex specific and not considered relevant to humans. The NOAEL in this study was 300 mg/kg.

 

Dermal

In a repeated-dose dermal study, neodecanoic acid was applied repeatedly (once daily for 10 applications with a rest period on days 5 and 6) to the skin of rabbits at doses of 0.5 or 2.5 ml/kg (400 or 2280 mg/kg/day).  All animals survived the exposure.  Wheezing was noted in one animal at the 0.5 ml dose level.  Animals at the lower dose level generally showed an overall body weight gain while those at the high level showed terminal weight losses.  The low level animals generally showed slight erythema and moderate atonia and desquamation following the first or fourth application and during the remainder of the study.  At the high level, moderate erythema and moderate or marked atonia and desquamation were present in all animals.  In addition, slight edema was present following the fifth application and slight fissures or cracks were observed in several animals following the last seven applications.  The exposed skin also became hypersensitive to the touch. There were no indications of systemic toxicity attributed to exposure.

 

A repeated dose dermal toxicity study was conducted for propanoic acid, 2,2-dimethyl- (CAS# 75-98-9) in male rabbits (Hazelton Laboratories Inc., 1964). Test material in isopropyl alcohol solution was repeatedly applied to the shaved intact skin of albino rabbits 5 days/week for two weeks (for a total of 10 applications) at doses of 30 or 300 mg/kg/day. Slight to moderate irritation at the low dose and moderate to marked irritation at the high dose was observed. Slight or moderate erythema, atonia, and desquamation were seen at the low dose. At the high dose, skin irritation consisted of moderate erythema, slight to marked edema, moderate or marked atonia and desquamation. Some dermal necrosis at the site of application was seen in three rabbits and persisted throughout the study. Control animals that received only the solvent (isopropyl alcohol) showed slight irritation. There were no signs of systemic toxicity attributable to dermal absorption of propanoic acid, 2,2-dimethyl-. The NOAEL for systemic toxicity in this study was 300 mg/kg.

 

Carboxylic acid, C6-8 neo (CAS# 95823-36-2) was applied at 55.4 mg/kg and 553.7 mg/kg to the shaved intact skin of rabbits for 10 applications (Hazleton Laboratories, Inc., 1964). No treatment related effects were observed on behaviour of clinical signs during the in-life phase of the study. Gross pathology of the animals in all dose groups did not reveal any abnormalities. Repeated application of carboxylic acid C6-8 neo did produce marked skin irritation with some dermal necrosis at the site of application in the high dose group. Since no systemic effects were observed in this study, the NOAEL for systemic effects following subchronic dermal application of carboxylic acid, C6-8 neo was 553.7 mg/kg.

 

Members of the Neo acid C5 to C28 Category have a low order of toxicity under conditions of repeat exposure by oral and dermal routes. In addition, they display a consistent degree of subchronic toxicity by either oral or dermal route of exposure. No classification for repeated dose toxicity is indicated according to the classification, labelling, and packaging (CLP) regulation (EC) No 1272/2008.

Zinc neodecanoate basic

Since no repeated dose toxicity study is available specifically for zinc neodecanoate basic, information on the individual assessment entities zinc and neodecanoate will be used for the hazard assessment and when applicable for the risk characterisation of zinc neodecanoate basic. For the purpose of hazard assessment of zinc neodecanoate basic, the point of departure for the most sensitive endpoint of each assessment entity will be used for the DNEL derivation. In case of neodecanoic acid in zinc neodecanoate basic, the NOAEL of 75 mg/kg bw/day for the reproductive toxicity will be used. For zinc the NOAEL of 0.83 mg/kg bw/day (human data) will be used.

Justification for classification or non-classification

In relevant and reliable repeated dose toxicity studies as well as human data for both entities formed upon dissolution of zinc neodecanoate basic, namely zinc and neodecanoate, there were no toxicological findings reported that would justify a classification for specific target organ toxicity with repeated exposure. Hence, no classification for zinc neodecanoate as STOT-RE,oral is required.

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