Magnesium neodecanoate

Endpoint summary

Description of key information

No repeated dose toxicity study with magnesium neodecanoate is available, thus the repeated dose toxicity will be addressed with existing data on the individual moieties magnesium and neodecanoic acid.

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

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 adverse effect observed

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 adverse effect observed

Additional information

No repeated dose toxicity study with magnesium neodecanoate is available, thus the repeated dose toxicity will be addressed with existing data on the individual moieties magnesium and neodecanoic acid.

Magnesium

Based on daily consumption of magnesium via drinking water, food and supplements, everyone is exposed to high concentrations of magnesium on a daily basis for the entire life. Magnesium is an essential element for many cellular processes for all species. In humans, mild diarrhoea is the most sensitive non-desirable effect of orally administered readily dissociable magnesium salts, because excessive magnesium is excreted via faeces. Eventually, not any of the plethora of human data sets available showed adverse effects upon chronic oral exposure.

 

Neodecanoic acid

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 phosphatase, cholesterol and bilirubin levels at the 100 and 300 mg/kg/day dose levels, and slight increase of alkaline phosphatase 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 was 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.

 

Repeated dose toxicity: 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.

Magnesium neodecanoate

As the two moieties of magnesium neodecanoate do not induce adverse effects in any relevant and reliable repeated dose toxicity studies, magnesium decanoate in all probability has also no potential to induce adverse effects after repeated exposure.

For the purpose of hazard assessment of magnesium neodecanoate, the point of departure for the most sensitive endpoint of each constituent will be used for the DNEL derivation. In case of neodecanoic acid in magnesium neodecanoate, the NOAEL of 75 mg/kg bw/day, the highest tested doese of a three-generation reproductive toxicity study, will be used.

Justification for classification or non-classification

As the two moieties of substance magnesium neodecanoate do not induce adverse effects leading to a STOT RE classification, magnesium neodecanoate in all probability has also no potential for systemic toxicity leading to a classification.

According to the criteria of REGULATION (EC) No 1272/2008 and its subsequent adaptions, magnesium neodecanoate does not have to be classified and has no obligatory labelling requirement for Specific target organ toxicity by repeated exposure (STOT-RE).