Oleic acid, copper salt

Endpoint summary

Description of key information

No acute toxicity studies with oleic acid, copper salts are available, thus the acute toxicity will be addressed with existing data on the individual moieties copper and oleic acid.

Signs of acute oral toxicity are not expected for the moiety oleic acid, since all oral LD50 for fatty acids tested were greater than 2000 mg/kg bw. The studies for moiety copper were assessed in a weight of evidence approach. The oral LD50 value is 197 mg Cu/kg bw. Further, copper sulphate is legally classified (Regulation 1272/2008; Index No. 029 -004 -00 -0) for acute oral toxicity category 4.

The calculated LD50 for oleic acid, copper salts is 300 < LD50 <= 2000, thus the substance is classified according to regulation (EC) 1272/2008 for acute oral toxicity category 4 (H302: Harmful if swallowed).

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No acute toxicity studies with oleic acid, copper salt are available, thus the acute toxicity will be addressed with existing data on the dissociation products copper and oleic acid.

Copper

Acute oral toxicity

Three relevant and reliable GLP studies (Lheritier 1994, Sanders 2001a, Sanders 2002) tested different copper substances in regard to acute oral toxicity. All studies were used in a weight of evidence approach. Sanders (2002) assessed acute oral toxicity of copper oxide in rats conducting a OECD No.423 study. The test substance showed no systemic toxicity and an LD50 >2500 mg/kg bw was determined. In contrast, Lheritier (1994) and Sanders (2001a) showed comparable results in regard to acute oral toxicity for copper sulphate and coated copper flakes, respectively. In a OECD No. 401 study, Sanders (2001) estimated an LD50 value in rats to be in the range of 300-500 mg/kg bw. Lheritier (1994) determined an LD50, for copper sulphate, in rats of about 481-482 mg/kg bw in a OECD No. 401 study. 

 

Oleic acid

Acute oral toxicity

A registration dossier shall contain information on the human health hazard assessment (regulation 1907/2006, Art.10). However, it is considered that the information requirements for oleic acid as laid down in annex VII to IX can be fulfilled by adaptation of the standard testing regime according to Annex XI, points 1.2. and 1.3. as presented in the following:

According to Regulation (EC) No 1907/2006 Annex V substances obtained from natural sources and not modified such as vegetable fats and oils as well as fatty acids from C6 to C24 and their potassium, sodium, calcium and magnesium salts are excluded from the obligation to register.

The substance subjected to registration is a monounsaturated C18- fatty acid. Based on this, the following endpoint is covered by publicly available data on fatty acids with the same or similar structure. Due to the structural similarity and the fact that only one hydrogenation of the double bond of oleic acid yields the saturated derivative stearic acid, most of the data are focused on stearic acid.

According to the HERA document on fatty acid salts “the available data for fatty acids provide a clear picture of low acute toxicity for this class of chemicals. All oral LD50 values were greater than 2,000 mg/kg, with little mortality being observed even at the highest doses tested in the studies (IUCLID, 2000c, 2000e, 2000f, 2000g; Clayton & Clayton, 1982; CIR, 1987). The available data for the fatty acid salts also indicate that these are of low acute toxicity. For example, an acute oral LD50 value of >5,000 mg/kg (highest dose tested) has been reported for sodium soap. This test was done according to GLP and OECD Guideline 401 (IUCLID, 2000f), while in another study also done to GLP and according to Directive 84/449/EEC, B.1, an LD50value of >2,000 mg/kg (highest dose tested) was reported for fatty acids, C16-18 and C18-unsat., sodium salts (IUCLID, 2000f)” (HERA, 2002).

“In an OECD TG 401 study, a group of five rats/sex was administered octadecanoic acid (as a 50% suspension in DMSO) at a dose of 5000 mg/kg bw. There was one death. Animals exhibited transient piloerection, excessive salivation, and diminished activity. At necropsy, the male animal that died exhibited a stomach full of test substance; surviving animals showed remnants of test substance in the stomach with swelling of the mucous membrane. The LD50 was > 5000 mg/kg bw” (OECD SIDS, 2014).

“International-BioResearch (1974, as referred to by CIR, 1987) determined the acute oral toxicity in groups of five male albino rats. Animals were administered by gavage lauric-, myristic-, palmitic- or stearic acid with increasing doses of up to 10,000 mg/kg bw and oleic acid up to 20,000 mg/kg bw. It was observed that for all these fatty acids the LD50value was above the maximum level tested. No mortality was observed in five albino rats gavaged with 5 g/kg bw oleic acid (commercially supplied); clinical signs were not reported during the 7-day post-exposure period (CTFA, 1978, as referred to in CIR, 1987)” (EFSA NDA Panel, 2017).

“Any toxic effects, such as excessive salivation, diarrhoea, central nervous system depression, loss of reflex actions or coma, shown at higher doses, decrease in severity with an increase in the chain length of the fatty acid (Pi-Sunyer et al., 1969). These reported effects are a result of the high doses administered and the fact that unlike humans rats don’t have a vomiting reflex. Therefore, these high dose effects are not considered relevant for human exposure” (HERA, 2002).

In conclusion, the conduct of any further toxicity studies with acute exposure in animals would not contribute any new information and is therefore not considered to be required.

 

Oleic acid, copper salts

Acute oral toxicity

Three relevant and reliable GLP studies (Lheritier 1994, Sanders 2001a, Sanders 2002) tested different copper substances for acute oral toxicity. All studies were used in a weight of evidence approach. Copper sulphate is characterized best and has an LD50 value of 481 mg/kg bw. Based on the assumption that copper is the moiety of concern and responsible for adverse effects observed, an LD50 value for copper of about 197.2 mg/kg bw could be calculated based on the molecular weight. Moreover, copper sulphate is legally binding classified (Regulation (EC) No. 1272/2008; Index No. 029-004-00-0) for acute oral toxicity category 4.

The LD50 for oleic acid, copper salts is based on the LD50 values of the assessment entities copper and oleic acid. Based on the oral LD50 value for copper of 197 mg Cu/kg bw and the oral LD50 values of oleic acid of >2000 mg/kg bw/day, the calculated LD50 for oleic acid, copper salts is 300 < LD50 <= 2000, thus the substance is classified according to regulation (EC) 1272/2008 for acute oral toxicity category 4 (H302: Harmful if swallowed).

For further information on the toxicity of the assessment entities, please refer to the relevant section in the IUCLID.

 

Justification for classification or non-classification

The calculated LD50 for oleic acid, copper salts is 300 < LD50 <= 2000, thus the substance is classified according to regulation (EC) 1272/2008 for acute oral toxicity category 4 (H302: Harmful if swallowed). No adverse effects were observed upon necropsy in the acute oral toxicity studies with the assessment entity copper or oleic acid that would justify a classification for specific target organ toxicity-single exposure.