Naphthenic acids, copper salts

Endpoint summary

Description of key information

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

Signs of acute oral and dermal toxicity are not expected for the moiety naphthenic acid, since the LD50 is 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 dermal LD50 value for copper is >2000 mg Cu/kg bw.

The calculated oral LD50 for naphthenic acids, 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).

The calculated dermal LD50 for naphthenic acids, copper salts is >2000 mg/kg bw, thus the substance is not classified for acute dermal toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

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 an OECD No.423 study. The test substance induced showed no systemic toxicity and a 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 an OECD No. 401 study, Sanders (2001) estimated a LD50 in rats to be in the range of 300-500 mg/kg bw. Lheritier (1994) determined a LD50, for copper sulphate, in rats of about 481-482 mg/kg bw in a OECD No. 401 study. 

Copper sulphate is characterized best and has a LD50 of 481 mg/kg bw. Based on the assumption that copper is the moiety of concern and responsible for adverse effects observed, a LD50 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 (H302: Harmful if swallowed). 

 

Acute dermal toxicity

Three relevant and reliable GLP studies (Lheritier 1993, Sanders 2001b, Sanders 2002) tested different copper substances in regard to acute dermal toxicity. All studies were used in a weight of evidence approach. All studies were performed in rats according to OECD test guideline No. 402. None of the copper substances tested showed acute dermal toxicity and, thus LD50 was determined to be greater than 2000 mg/kg bw. All studies were used in a weight of evidence approach. The LD50 for copper salt is set accordingly to be greater than 2000 mg/kg bw.

 

Naphthenate

Acute oral toxicity was obtained from various studies, that were considered as Weight of Evidence information. There were various studies with limited to moderate information, however all providing consistent LD50 values:

- LD50 = 5.88 g/kg bw in male rats; male rats were dosed from 1 to 10 g/kg of body weights (HPVIS, 2003; Exxon, 1979). Deaths occurred at the four highest dose levels of 3.26, 4.64, 6.81, and 10 g/kg bw. 8/10 animals died at the two highest dose levels. Significant predeath toxic signs included tremors, lethargy, ptosis, ataxia, prostration, negative righting reflex, flaccid muscle tone, piloerection, diarrhea, chromodacryorrhea, dyspnea and chromorhinorrhea. Body weight changes were noted in the survivors. Necropsy findings in the animals that died during the study included dilated hearts and gastrointestinal irregularities.

- LD50 = 3.0 -5.2 g/kg bw in rats; this was based on fraction from crude kerosene acids and a fraction from mixed crude oils, respectively (Rockhold, 1955) . Death appeared to result from gastrointestinal disturbances, with the mortality peak occurring on the third to fourth day after administration. The animals exhibited anorexia, inanition, diarrhea, and asthenia.

- LD50 = 3.55 g/kg bw in mice (HPVIS, 2003; Penissi & Lynch, 1977). Clinical observations included CNS depression, corneal eye opacity,dryness of mouth, convulsions, diarrhea, and death due to respiratory arrest

- Finally acute oral toxicity testing was performed in Wistar rats with a mixture of naphthenic acids isolated from Althabasca oils sand (AOS). Single dosages of 3, 30 and 300 mg/kg bw were given to female rats and 300 mg/kg bw was given to male rats by oral gavage. Food consumption was temporarily suppressed in the high dose groups of both sexes. Histopathology 14 days after dosing revealed a significant incidence of pericholangitis in the high dose group of both sexes, suggesting hepatotoxicity as an acute effect. Other histological lesions included brain haemorrhage in the high dosed males, and cardiac perioarteriolar necrosis and fibrosis in female rats. *

 

Acute dermal toxicity was studied after 24 hours occlusive dressing in 2 studies in New Zealand rabbits:

- LD50 >3.16 g/kg (HPVIS, 2003; Exxon, 1979). No deaths occurred at the 3.16 mg/kg dose level and most of the animals (3/4) appeared normal during the first 2 to 4 hours of dosing, after which symptoms of toxicity were observed, e.g. lethargy, diarrhea, ptosis, adipsia, anorexia, and few feces.

- LD50> 20 g/kg bw (Auletta, 1979).Ataxia and motor activity decrease were evident throughout the fourteen day observation period; from Day 2 through Day 14 of the study these signs were noted at least once in all animals; abdominal griping and soft stool were noted in a few animals and oral, ocular and nasal discharge, alopecia, aggressiveness and fecal staining of the abdomen were noted sporadically in one or two animals.

 

 

Naphthenic acids, copper salts

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

The oral LD50 for naphthenic acids, copper salts is based on the LD50 values of the assessment entities copper and naphthenic acid. Based on the oral LD50 value for copper of 197 mg Cu/kg bw and the oral LD50 values of naphthenic acid of >2000 mg/kg bw, the calculated LD50 for naphthenic acids, 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).

The dermal LD50 for naphthenic acids, copper salts is based on the LD50 values of the assessment entities copper and naphthenic acid. Based on the dermal LD50 value for copper of >2000 mg Cu/kg bw and the dermal LD50 values of naphthenic acid of >2000 mg/kg bw, the calculated dermal LD50 for naphthenic acids, copper salts is >2000 mg/kg bw, thus the substance is not classified for acute dermal toxicity.

 

For further information on the toxicity of the individual moieties, please refer to the relevant sections in the IUCLID and CSR.

Justification for classification or non-classification

The calculated oral LD50 for naphthenic acids, 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).

The calculated dermal LD50 for naphthenic acids, copper salts is >2000 mg/kg bw, thus the substance is not classified for acute oral toxicity.

No adverse effects were observed upon necropsy in the acute oral and dermal toxicity studies with the assessment entity copper or naphthenic acid that would justify a classification for specific target organ toxicity-single exposure.