Fatty acids, C9-13-neo-, barium salts

Endpoint summary

Description of key information

No repeated dose toxicity study with fatty acids, C9-13-neo-, barium salts is available, thus the repeated dose toxicity will be addressed with existing data on the individual assessment entities barium and neodecanoate.As the two moieties of fatty acids, C9-13-neo-, barium salts do not induce adverse effects, fatty acids, C9-13-neo-, barium salts in all probability has also no potential for systemic toxicity leading to a classification.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

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

Barium

Repeated dose toxicity, oral, rat

Comparing the results of the different oral studies it becomes obvious that the findings of all these studies are not contradictory. The studies conducted by NTP (1994) and Dietz and co-workers (1992) in rats and mice found similar targets of toxicity; although some differences in sensitivity were found. The main adverse effect caused by barium chloride was the nephrotoxicity in rats and mice of both sexes.

The available data in laboratory animals suggest that the toxicity of ingested barium is similar across species. The lowest NOAEL for nephrotoxic effects in rats or mice were identified from the 13-week drinking water study by Dietz et al. (1992) as the NOAEL of 61 mg Ba/kg bw/d in male rats and 81 mg/kg bw/d in female rats and of about 165 mg Ba/kg bw/d in male mice and 166 mg Ba/kg bw/d in female mice.

The no-observable-effect concentration of the 13-weeks NTP study (1994) conducted with barium chloride was estimated to be 2000 ppm as based on changes of the final mean body weights, mean body weight gains, mortality, and renal toxicity at 4000 ppm in both species (LOAEL). The dose of 2,000 ppm represents the NOAEL value of this study corresponding to 62.0 and 65.3 mg Ba/kg bw/d in male and female rats, respectively. Thus, the dose of 62.0mg Ba/kg bw/d in male rats and 65.3 mg Ba/kg bw/d in female rats can be regarded as relevant NOAEL for chronic barium toxicity in this 13-week study.

Taken the results for male and female rats from both studies (NTP and Dietz et.al) into consideration, an average NOAEL could safely be calculated at 61.5 mg Ba/kg bw/d, which results in a re-calculated value of 93.3 mg/kg bw/d for barium chloride.

It is explicitly noted that according to the precautionary principle the “worst case value” of 61 mg Ba/kg bw/d (in male rats according to Dietz et al.) is used for the derivation of DNELs. This value refers to approx. 92.5 mg BaCl2/ kg bw/d. However, for classification and labelling purposes it appears appropriate to consider all relevant data on repeated dose oral toxicity. As already mentioned above, the results of the NTP study (1994) and the study performed by Dietz et al. (1992) are not contradictory, and in both investigations similar target organs of toxicity were found and no differences in susceptibility of gender was seen. Therefore, it could safely be stated that the calculation of an average value, using the NOAELs for male and female rats coming from the NTP and the Dietz studies, is considered to be a valid approach for the classification and labelling discussion.

 

 

 

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.

 

Fatty acids, C9-13-neo-, barium salts

Since no repeated dose toxicity study is available specifically for fatty acids, C9-13-neo-, barium salts, information on the individual moieties barium and neodecanoate will be used for the hazard assessment and when applicable for the risk characterisation of fatty acids, C9-13-neo-, barium salts. The assessment entity representative for fatty acids, C9-13-neo- have a low order of toxicity under conditions of repeat exposure by oral and dermal routes. In addition, they display a consistent degree of sub-chronic toxicity by either oral or dermal route of exposure. The assessment entity barium showed changes of the final mean body weights, mean body weight gains, mortality, and renal toxicity. For further information on the toxicity of the assessment entities, please refer to the relevant sections in the IUCLID and CSR. For the purpose of hazard assessment of fatty acids, C9-13-neo-, barium salts, the point of departure for the most sensitive endpoint of each moiety will be used for the DNEL derivation. In case of neodecanoic acid in fatty acids, C9-13-neo-, barium salts, the NOAEL of 75 mg/kg bw/day for the reproductive toxicity will be used. In case of barium the NOAEL of 61.0 mg/kg bw/day obtained in a repeated dose toxicity study will be used. 

Justification for classification or non-classification

The adverse effects were observed for the assessment entities barium and neodecanoate do not meet the classification criteria since no severe adverse effects were observed at the guidance value, oral for a Category 1 classification of 10 mg/kg bw/day and at the guidance value for a Category 2 classification of 100 mg/kg bw/day, hence no classification required for fatty acids, C9-13-neo-, barium salts.