Naphthenic acids, copper salts

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Although the information is only available as a published peer reviewed article which does not mention GLP compliance of the studies enough details are provided to adequately interprete the obtained data.

Data source

Reference

Reference Type:

publication

Title:

Allegernicity and cross-reactivity of naphthenic acid and its metallic salts in experimental animals

Author:

Yamato T., Shimizu M, Noda T.

Year:

2006

Bibliographic source:

Contact Dermatitis, 2006, 54, 25-28

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Although no guideline was followed the methods and results are well described allowing a detailed interpretation of the results.
The most inmportant deviation is the number of animals per group. In this test 5 in stead of the recommended minimum of 10 animals have been used. Next to this also the non-reporting of the performance of the positive control is deviating from the guideline.

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Since the LLNA is the preferred method for new in vivo testing, the use of the standard guinea pig tests to obtain new data on the skin sensitisation potential of a substance will be acceptable only in exceptional circumstances and will require scientific justification. However, existing data of good quality that were generated before 10 May 2017, or for which the study was initiated before 10 May 2017, and derived from such tests are acceptable; and if these tests provide clear results that are adequate for classification, even when a conclusion on potency (Cat. 1A or not) cannot be drawn, they will preclude the need for further in vivo testing.

Test material

Test material information

Constituent 1

Reference substance name:

Naphthenic acids

EC Number:

215-662-8

EC Name:

Naphthenic acids

Cas Number:

1338-24-5

Molecular formula:

For the acidic (naphthenic) fraction: CnH2n+zO2, where n = carbon number and z = homologous group series number: z = 0 when no ring structures are present, z = -2 when 1 ring is present, z = -4 when 2 rings are present etc. For the non-acidic fraction: not applicable

IUPAC Name:

Naphthenic acids, consisting of an acidic (naphthenic) fraction (70-95%) composed mainly of C8-C20 and 0-3 rings and a non-acidic (petroleum) fraction (5-30%), composed mainly of C12-C22, <10% aromatics, with a boiling range of approximately 160-350°C.

Test material form:

other: liquid

Details on test material:

Chemical obtained from Wako Pure Chemical Industries (Osaka Japan)
Next to naphthenic acid also cobalt naphthenate, copper naphthenate and zinc napthtenate have been investigated using the Guinea pig maximization test.

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

female

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

epicutaneous, open

Vehicle:

other:

Induction 2

Concentration / amount:

1%, 25% as induction; 0.5% as challenge dose

Challenge

Challenge 1

Route:

epicutaneous, open

Vehicle:

other:

Challenge 2

Concentration / amount:

1%, 25% as induction; 0.5% as challenge dose

No. of animals per dose:

5

Details on study design:

6-week-old female Hartley guinea pigs from Japan SLC (Shizuoka, Japan) were used The GPMT was performed as described previously in the literature 5 animals were used for each sensitization group (CuN, CoN, ZnN and Ν A) The first induction dose was set at 1%, while the second induction dose was 25%. 2 weeks after the second induction, 0.1 ml aliquots of the 7 chemicals in vehicles (0.5% in petroleum ether for CuN, CoN. ZnN and NA, 1% in ethanol for C0CI2. CuCL and ZnCU) were applied to a shaved area of the fiank for challenge all at once. 2 D after the challenge, each site was scored according to the criteria of Sato et al. (*). 1 week later, CoN-sensitized animals were further challenged with various concentrations of CoN and C0CI2 for a dose-response study.
* Sato Y. Katsumura Y. Ichikawa H. Kobayashi T. Kozuka T. Morikawa F. Ohta S. A modilied tcchnique of guinea pig testing to identify delayed hypersensitivity allergens. Contact Dermatitis 1981: 7: 225 237.

Positive control substance(s):

not specified

Results and discussion

Positive control results:

Not reported

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

48

Group:

negative control

Dose level:

0

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0.

Results 2

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.5%

No. with + reactions:

4

Total no. in group:

5

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5%. No with. + reactions: 4.0. Total no. in groups: 5.0.

Results 3

Reading:

1st reading

Hours after challenge:

48

Group:

positive control

Remarks on result:

other: not reported

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Althought there are only a limited numer of animals used per group the sensitizing properties of this substance were clearly positive.

Executive summary:

A GPMT test in 6-week-old female Hartley guinea pigs was performed with Natphenic acids and salts (copper, zin and cobalt naphthenate). The first induction dose was set at 1%, while the second induction dose was 25%. Two weeks after the second induction, 0.1 ml aliquots of the 7 chemicals in vehicles (0.5% in petroleum ether for CuN, CoN. ZnN and NA) were applied to a shaved area of the fiank for challenge. Each site was scored 48 hours after challenge. Napthenic acid resulted in 4/5 animals with clear reactions at 48 hours, therefore it is considered to be sensitizing for skin.