Naphthenic acids, nickel salts

Endpoint summary

Description of key information

No acute toxicity studies with naphthenic acids, nickel salts are available, thus the acute toxicity will be addressed with existing data on the assessment entities nickel and naphthenic acid.

No adverse effects were observed in acute oral toxicity studies with the moiety naphthenate. However, two studies with the moiety nickel are available. An LD50 for acute oral toxicity of 361.9 mg NiSO4.6H2O/kg bw from the EPSL (2009a) study and a NOAEL of 100 mg NiSO4.6H2O/kg (or 22 mg Ni/kg) (FDRL, 1983) have been identified.

Thus,naphthenic acids, nickel salts is classified as acute toxic via the oral route Category 4 according to the Regulation (EC) 1272/2008 and subsequent adaptations (Cat.4; H302).

The calculated dermal LD50 for naphthenic acids, nickel 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

Nickel

Acute oral toxicity

Two studies with the assssment entity nickel are available. In the FRDL study, a NOAEL of 100 mg NiSO4.6H2O/kg (or 22 mg Ni/kg) (FDRL, 1983) was identified. Classification based on this study was confirmed by a GLP OECD guideline compliant acute oral toxicity test (Up and Down Procedure) in rats with nickel sulfate hexahydrate to produce toxicity from a single dose via the oral route. Under the conditions of this study, the acute oral LD50 of the test substance is estimated to be 361.9 mg/kg (based on maximum likelihood) of body weight in female rats. (EPSL, 2009)

 

Acute dermal toxicity

There are no available data on which to evaluate acute dermal toxicity. However, acute toxicity is expected to be low in view of the poor absorption by this route.

No risk characterisation will be conducted for acute dermal toxicity. Acute systemic effects are not relevant due to the very low dermal absorption of nickel. Acute local effects are covered by the long term DNEL based on prevention of dermal sensitization.

Naphthenate

Acute oral toxicity

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

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, nickel salts

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

The acute toxicity for naphthenic acids, nickel salts will be addressed based on the toxicological information for the assessment entity nickel, which is classified as acute toxic via the oral route Category 4 based on the acute oral toxicity studies with an LD50 of 361.9 mg NiSO4.6H2O from the EPSL (2009a) study and of 100 mg NiSO4.6H2O/kg bw (22 mg Ni/kg bw/day from the FDRL (1983) study.

Naphthenic acid can safely be assumed having a significantly lower human health hazard potential than nickel. Consequently, the assessment entity nickel is considered the toxicological driver for the acute toxicity for naphthenic acids, nickel salts.

The dermal LD50 for naphthenic acids, nickel salts is based on the LD50 values of the assessment entities nickel and naphthenic acid. Based on the low absorption for nickel and the dermal LD50 values of naphthenic acid of >2000 mg/kg bw, the calculated dermal LD50 for naphthenic acids, nickel 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 acute toxicity for naphthenic acids, nickel salts will be addressed based on the toxicological information for the assessment entity nickel. Thus, naphthenic acids, nickel salts is classified as acute toxic via the oral route Category 4 according to the Regulation (EC) 1272/2008 and subsequent adaptations (Cat.4; H302).

Naphthenic acid can safely be assumed having a significantly lower human health hazard potential than nickel. Consequently, the assessment entity nickel is considered the toxicological driver for classification. The classification for naphthenic acids, nickel salts will be derived by using the nickel NOAEL values and apply a stoichiometric correction on the basis of the maximum nickel content of 10.8% in accordance with the mixture rules.

 

The calculated dermal LD50 for naphthenic acids, nickel 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 nickel or naphthenic acid that would justify a classification for specific target organ toxicity-single exposure.