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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
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 interpret the obtained data. The following information are not given: environmental conditions of the animals, whether females were nulliparous and non-pregnant, acclimatisation period of the animals, body weight at the beginning and the end of the study, historical control data for positive control substance, details on test substances used, animal number per test group is less than 10, details on skin reaction to the induction dose (induction dose should cause mild-to-moderate skin irritation), no second observation has been performed after 72 hours, no details on individual scorings.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Allegernicity and cross-reactivity of naphthenic acid and its metallic salts in experimental animals
Author:
Yamano T., Shimizu M, Noda T.
Year:
2006
Bibliographic source:
Contact Dermatitis, 2006, 54, 25-28
Reference Type:
publication
Title:
A new protocol and criteria for quantitative determination of sensitization potencies of chemicals by guinea pig maximisation test
Author:
Nakamura, A. et al.
Year:
1994
Bibliographic source:
Contact Dermatitis, 1994, 31, 72-85

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
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 important deviation is the number of animals per group. In this test 5 instead 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
Remarks:
data accessed from publication
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Already existing study. The LLNA 429 was not formally adopted by the OECD until 22 July 2010.

Test material

Constituent 1
Reference substance name:
Naphthenic acids, zinc salts
EC Number:
234-409-2
EC Name:
Naphthenic acids, zinc salts
Cas Number:
12001-85-3
IUPAC Name:
zinc bis[3-(3-ethylcyclopentyl)propanoate]
Details on test material:
Fatty acids, zinc salts:
Source: Tokyo Kasei Kogyo (Tokyo, Japan)
Purity: superior grade
Zinc content: 9.5-10.5%

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Japan SLC (Shizuoka, Japan)
- Age: 6 weeks

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, open
Concentration / amount:
First induction: 1%
Second induction: 25%
Challenge
No.:
#1
Route:
epicutaneous, open
Vehicle:
other: 0.5% in petroleum ether
Concentration / amount:
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 both sensitization groups. 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 test substance in vehicle (0.5% in petroleum ether) was applied to a shaved area of the flank for challenge. 2 days after the challenge, each site was scored according to the criteria of Sato et al.

Additional information:
As mentioned in the material and method section, the test was performed as described in Nakamura et al. (1994) (see linked reference). In this reference the following additional information is given:
- Exposure duration: 24 hours
- challenge was perfomed by the open patch test method
- the selected challenge concentration was lower than the irritant concentrations
- time until challenge: 21 days after the initial induction dose (this leads to the conclusion that 7 days were between the first and second induction dose)
- the total erythema and edema scores were summed in each group of animals. The total score was divided by the number of animals in the group to give the mean response induced by the given concentration for induction and challenge. The number of positive sites was divided by the numer of animals of the group to give the sensitization rate.

Reference:
* 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.
Challenge controls:
none
Positive control substance(s):
not specified

Results and discussion

Positive control results:
Not reported

In vivo (non-LLNA)

Resultsopen allclose all
Key result
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: Vehicle
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.5%
No. with + reactions:
3
Total no. in group:
5
Clinical observations:
median skin reaction score: 1
Remarks on result:
other: Naphthenic acid, zinc salts
Reading:
1st reading
Hours after challenge:
48
Group:
positive control
Remarks on result:
not measured/tested

Applicant's summary and conclusion

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
A GPMT test in 6-week-old female Hartley guinea pigs was performed with Naphthenic acid, zinc salts. 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 test substances in vehicle (0.5% in petroleum ether) was applied to a shaved area of the flank for challenge. Each site was scored 48 hours after challenge. Naphthenic acid, zinc salts resulted in 3/5 animals with clear reactions at 48 hours, therefore the substance is considered to be sensitizing for skin.

Although the information is only available as a published peer reviewed article which does not mention GLP compliance of the studies and some information were not provided, enough details are provided to adequately interpret the obtained data and to conclude that both substances seem to have skin sensitising potential.

The following information are not given: environmental conditions of the animals, whether females were nulliparous and non-pregnant, acclimatisation period of the animals, body weight at the beginning and the end of the study, historical control data for positive control substances, details on test substance used, animal number per test group is less than 10, details on skin reaction to the induction dose (induction dose should cause mild-to-moderate skin irritation), no second observation has been performed after 72 hours, no details on individual scorings.
Executive summary:

A GPMT test in 6-week-old female Hartley guinea pigs was performed with Naphthenic acid, zinc salts. 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 test substance in vehicle (0.5% in petroleum ether) was applied to a shaved area of the flank for challenge. Each site was scored 48 hours after challenge. Naphthenic acid, zinc salts resulted in 3/5 animals with clear reactions at 48 hours, therefore the substance is considered to be sensitizing for skin. However, the number of animals per group is too low to obtain information about the potency of the sensitisation effect.