Hexachloroiridic acid

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 January 1989 – 16 January 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline study, to GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Hexachloroiridic acid

EC Number:

241-012-8

EC Name:

Hexachloroiridic acid

Cas Number:

16941-92-7

Molecular formula:

Cl6Ir.2H

IUPAC Name:

hexachloroiridium(2-);hydron

Test material form:

solid: crystalline

Details on test material:

- Name of test material (as cited in study report): chloroiridic acid
- Molecular formula (if other than submission substance): H2IrCl6.6H20
- Substance type: brown crystals
- Physical state: solid
- Analytical purity: ca. 38% Ir
- Lot/batch No.: 6767
- Storage condition of test material: room temperature
- Other: soluble in water, strongly acidic

Test animals

Species:

rabbit

Strain:

other: White Russian (albino)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: ASTA Pharma AG, D-4800 Bielefeld 14
- Age at study initiation: 10 months
- Weight at study initiation: 3 kg
- Housing: 1 rabbit in a stainless steel cage with a grating floor
- Diet: approx. 120 g/day/animal of a standard diet, ssniff K (“special diet for rabbits”) from Ssniff Spezialfutter GmbH
- Water: ad libitum
- Acclimation period: 1 day under test conditions before application of the material.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Humidity (%): 45-55
- Photoperiod (hrs dark / hrs light): 6am-6pm artificial lighting, 6pm-6am “natural light-dark-rhythm”

Test system

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):0.5 g moistened with 0.1 ml demineralized water

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Purity: demineralized

Duration of treatment / exposure:

4 hrs

Observation period:

6 days post application

Number of animals:

One female

Details on study design:

TEST SITE
- Area of exposure: approx. 6.25 cm2
- Type of wrap if used: A linen cloth adhered to a synthetic film glue and a bandage (Acrylastic, No. 2408, width 8 cm, P.Beiersdorf & Co. AG, Hamburg) wrapped several times around the trunk.

REMOVAL OF TEST SUBSTANCE
- Washing: remaining test material gently washed off as far as possible.
- Time after start of exposure: 4 hrs

SCORING SYSTEM: The irritation index on the intact skin was “assessed by a modified method according to Gilman et al.” 1983. Erythema, eschar and oedema formation were assessed using the Draize method 1, 24, 48 and 72 hr after removal of the patch and, thereafter once daily for 6 days. In addition, further reactions on the skin (e.g. corrosive effects) as well as clinical symptoms (systemic toxic effects) were noted. The animal was sacrificed after 6 days of observation and a sample of the skin was examined microscopically. No irritation index was determined because of the corrosive effects.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24 and 48 hrs after termination of exposure

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 4 days

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 48 hrs after termination of exposure

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 4 days

Irritant / corrosive response data:

Microscopic examination revealed “coagulation necrosis of the upper third to half of the corium, including skin adnexae, with complete loss of the epidermal epithelium and demarcation to the lower corium by a wall of inflammatory cells (predominantly granulocytes) and cell detritus. Reactive inflammation at the border to the intact skin occurred.” Chloroiridic acid was, therefore, found to be corrosive.

Other effects:

Discoloration of the treated skin area (black, partially changing to brown during days 1-3 of observation) was noted, along with deepened spots (to a depth of 2 mm) 1 day after treatment which progressed to eschar formation later on. There was no evidence of systemic toxicity.

Any other information on results incl. tables

Table 1: Irritant/corrosive response data for animal no. 2010 at each observation time.Test substance:chloroiridic acid

Score at time point / Reversibility	Erythema and Eschar formation:	Edema
60 min	1	1
24 h	2	2
48 h	2	3
72 h	1	2
4 d	1	2

The areas not treated with the test substance did not show any reactions

Table 2:         Microscopical Examination of the Skin: Test Substance: Chloroiridic acid

 

Skin Section                           Findings

Animal No. 2010   - coagulation necrosis of the upper third to half of the corium, including skin adnexae, with complete loss of epidermal epithelium

- demarcation to the lower corium by a wall of inflammatory cells (predominantly granulocytes) and cell detritus

- reactive inflammation at the border to the intact skin

Applicant's summary and conclusion

Interpretation of results:

Category 1C (corrosive) based on GHS criteria

Conclusions:

In a guideline study, to GLP, chloroiridic acid (0.5 g) produced well defined erythema (grade 2), moderate oedema (grade 3) and was corrosive to the shorn, intact skin of one female rabbit following 4hr occluded application.

Executive summary:

In an in vivo skin irritation assay, conducted according to OECD Test Guideline 404, and to GLP, chloroiridic acid (0.5 g) was applied (occluded) to the shorn, intact skin of one female albino rabbit.

After 4 hrs, the dressing was removed, the remaining test material was gently washed off and the skin site qualitatively and quantitatively assessed for erythema (and eschar) and oedema formation using the Draize method. Observations were again made 1, 24, 48 and 72 hrs later, as well as once daily for 6 days. After 6 days of observation, the animal was sacrificed and the skin was examined microscopically.

Well defined erythema and moderate oedema were noted and chloroiridic acid was classified as corrosive. Due to these effects, an irritation index was not determined. Deepened spots leading to eschar formation were seen but no systemic toxicity was detected.