Naphthenic acids, cobalt salts

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

no data available

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Reasonably well conducted study. Positive controls are not given. Test procedure with modification of the standard LLNA, but according to the author, the used method have comparable sensitivity to the radioactive original method.

Qualifier:

no guideline followed

Principles of method if other than guideline:

The method to test the reactivity of CoCl2 was performed by the modified method of the standard LLNA with some modification.

GLP compliance:

no

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

Balb/c

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: CLEA Japan (Tokyo, Japan)
No details are given.

Vehicle:

other: petrolatum

Concentration:

25 µL of 0.3%, 1%, 3% or 10%

No. of animals per dose:

4 mice

Details on study design:

RANGE FINDING TESTS:
No data available, if a range finding test was performed.

MAIN STUDY
TREATMENT PREPARATION AND ADMINISTRATION: Mice were exposed to 25 µL of various concentrations through application to the dorsum of both ears for 3 consecutive days (days 0-2). On day 4, 5-bromo-2'-deoxyuridine (BrdU) was administered i.p. to each mouse. The next day, a pair of auricular lymph nodes from each mouse was excised. After counting the total cell numbers from each mouse, BrdU concentrations were measured by enzyme-linked immunosorbent assay.

EVALUATION
Total lymph node cell count in a dosed animal divided by mean lymph node cell count in a control group was designated as a cellularity index, whereas BrdU incorporation per unit number of cells from a dosed animal divided by mean BrdU incorporation from a control group was used as a BrdU.incorporation index. A LLNA-stimulation index was calculated by multiplying the cellularity indey by the BrdU-incorporation index. At the time of lymph node excision, the thickness of the ears was measured with a digital micrometer. Ear thickness of a dosed animal divided by mean ear thickness of a control group was designated as ear-thickness index.

Positive control substance(s):

not specified

Statistics:

Index values for each dosed group and vehicle-control group were compared via Dunnett's or Steel's multiple comparison method using a Statlight software package.

Positive control results:

no data

Key result

Parameter:

SI

Value:

ca. 1.75

Test group / Remarks:

1 % concentration

Remarks on result:

other: Test substance exhibited significant increase in the LLNA-stimulation index values at the respective highest doses tested. Minimum induction dose for Cobalt naphthenate was 1% (see attached figure).

Key result

Parameter:

SI

Value:

ca. 12

Test group / Remarks:

3 % concentration

Key result

Parameter:

SI

Value:

ca. 12.5

Test group / Remarks:

10 % concentration

Interpretation of results:

other: potential skin sensitiser

Conclusions:

Cobalt naphthenate applied in concentration >1% can be evaluated as a potential skin sensitiser.

Executive summary:

Female BALB/c mice (4 per group) were treated with 25 µl of various concentrations (0.3, 1, 3 and 10 %) of Cobalt naphthenate in pet. or with petrolatum alone (vehicle control). The test substance was applied to the dorsum of both ears for 3 days. On day 4, 5-bromo-2'-deoxyuridine (BrdU) was administered i.p. The next day, a pair of auricular lymph nodes were excised. Total cell numer was counted and total BrdU concentrations were measured by enzyme-linked immunosorbent assay.A stimulation index was determined: BrdU incorporation per unit number of cells from treated animals compared to controls.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Migrated from Short description of key information:
Under the experimental conditions, the test item cobalt naphthenate induced delayed contact hypersensitivity in the murine Local Lymph Node Assay.

Justification for selection of skin sensitisation endpoint:
Key study.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Migrated from Short description of key information:
There is no known direct experience or information implicating this substance as occupational respiratory sensitisers. For further information please refer to the document attached to the endpoint summary in IUCLID section 7.4 (Sensitisation) or the respective appendix of the CSR.

Justification for classification or non-classification

Skin Sensitisation

The reference Yamano (2006) is considered as the key study on skin sensitisation and will be used for classification. The overall sensitisation results are as follows:Test substance exhibited significant increase in the LLNA-stimulation index values at the respective highest doses tested. Minimum induction dose for cobalt naphthenate was 1%. The classification criteria acc. to regulation (EC) 1272/2008 as skin sensitiser are met. Cobalt naphthenate will be classified as skin sensitiser category 1 (H317).

Respiratory sensitisation

There is no known direct experience or information implicating this substance as occupational respiratory sensitizers, thus classification criteria according to regulation (EC) 1272/2008 as respiratory sensitiser are not met.