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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study apparently performed according to the method described in Federal Register 1973, Vol. 38, No. 187, Section 1500: 41, which has some significant deviations from current OECD guidelines.
Remarks:
Certain of these deviations are likely to increase the possibility of an irritant reaction.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report Date:
1978

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Skin irritation patch test, as described in Federal Register 1973, Vol. 38, No. 187, Section 1500: 41.
Deviations:
not specified
Principles of method if other than guideline:
0.5 g of material was applied on a gauze pad to abraded and non-abraded skin of six albino rabbits. The site was covered with adhesive tape. The sites were examined after 24 and 72 hours for erythema and oedema.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Ammonium hexachloroplatinate
- Substance type: yellow powder
- Physical state: solid
- Lot/batch No.: 57662

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: “recognised breeders”
- Age at study initiation: 16-18 weeks
- Weight at study initiation: 2.3 kg (average)
- Diet: ad libitum commercial rabbit diet from Rank Hovis MacDougal
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): “Natural lighting conditions”

Test system

Type of coverage:
occlusive
Preparation of test site:
other: Backs of the rabbits were shaved (not “closely clipped” as recommended by the OECD guidelines). One site of each rabbit was abraded immediately before application of the test material, the other site remained intact.
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
Duration of treatment / exposure:
24 hrs
Observation period:
48 hrs
Number of animals:
Six females
Details on study design:
TEST SITE
- Area of exposure: Each site 2.5 cm2 (one intact, one abraded)
- Type of wrap if used: Gauze pad was secured by “Sleek” tape (evidently a waterproof tape)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): None

SCORING SYSTEM: Erythema (and eschar) formation and oedema formation were assessed on the intact and abraded skin of six rabbits at 24 and 72 hrs after initial application of the test compound (i.e. as soon as the dressing was removed and again 48 hrs later). The primary irritation index was calculated by adding the four values for erythema (and eschar) formation to the four for oedema formation, and dividing the total by four. According to the study report, Draize (1959) considers that “compounds producing combined averages (primary irritation indices) of 2 or less are only mildly irritating; whereas those with indices of 2 to 5 are moderate irritants, and those with scores above 6 are considered severe irritants”.

Results and discussion

In vivo

Results
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 72 hrs after initial application
Score:
1.3
Max. score:
8
Reversibility:
other: Reversibility not assessed, as observation period only 48 hrs (not up to 14 days as recommended in the OECD guidelines)
Other effects:
“Two abraded sites showed evidence of changes, possibly necrosis, associated with the abrasions in the skin”. The systemic toxicity was not reported.

Any other information on results incl. tables

Table: Individual animal scores for each time point

 Animal number  Time/hr  Erythema     Oedema   
     Abraded skin  Intact skin  Abraded skin  Intact skin
 1  24  1  0  0  0
   72  2  0  1  0
 2  24  0  0  0  0
   72  0  0  0  0
 3  24  1  0  1  0
   72  1  0  0  0
 4  24  2  2  2  1
   72  N2  1  1  0
 5  24  N2  1  2  1
   72  N2  0  1  0
 6  24  1  1  0  0
   72  0  0  0  0

 

N: Necrosis associated with abrasions

Applicant's summary and conclusion

Interpretation of results:
slightly irritating
Remarks:
Migrated information not irritant by EU criteria Criteria used for interpretation of results: other: Classified “according to the US Federal Register 1973 skin test”
Conclusions:
In an early US guideline study, ammonium hexachloroplatinate (0.5 g) was applied (24-hr, occluded) to the shaved abraded and intact skin of six rabbits. Slight but reversible indications of irritation to intact skin were observed in three animals during the observation period.
Executive summary:

In a US Federal Register Patch Test (1973), the skin irritant potential of ammonium hexachloroplatinate was assessed in six female New Zealand White rabbits. The test material (0.5 g) was applied (occluded) to the shaved abraded and intact skin for 24 hr.The sites were assessedfor evidence of erythema (and eschar) formation and oedema formation immediately upon removal of the patch, and again 48 hr later.

 

Three intact skin sites showed evidence of erythema/oedema which was observed to be reversible (or showed indications of reversibility) during the observation period. No signs of irritation were apparent on the other three intact sites. Two abraded skin sites showed evidence of possible necrosis associated with the abrasions in the skin.A Primary Irritation Score of 1.3 (out of 8) was obtained. The study authors classified ammonium hexachloroplatinate as a mild skin irritant in this test system.

 

This study suffered from a number of significant deviations from those given in the current OECD guidelines, including use of abraded skin, no moistening of test substance (a powder) to ensure good skin contact, a longer exposure period and failure to wash off any residual test material after removal of patch, observation period was insufficient to assess reversibility of effects, and skin was only examined on 2 occasions, at 0 and 48 hrs, rather than at 1, 24, 48 and 72 hrs, after patch removal. However, certain of these deviations are likely to increase the possibility of an irritant reaction, so the study can be considered as likely more sensitive than the current methodology to identify potential irritants.

 

Based on the results of this study, no classification for skin irritation is required under EU CLP criteria (EC 1272/2008).