Hexachloroiridic acid

Endpoint summary

Description of key information

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 (Zechel, 1989).
In accordance with Column 2, Annexes VII & VIII, no eye irritation studies were conducted as the criteria are met for classification as corrosive to the skin.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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”

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.

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

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.

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

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as skin corrosion, leading to classification as serious eye damage (Category 1)

the study does not need to be conducted because the substance is a strong acid (pH <= 2.0) or base (pH => 11.5) and the available information indicates that it should be classified as serious eye damage (Category 1)

Endpoint conclusion

Endpoint conclusion:

no study available

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No data were identified in humans relating to skin or eye irritation, and no human or animal data in relation to respiratory irritation were found.

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 (Zechel, 1989).

Justification for selection of skin irritation / corrosion endpoint:
Only one, good quality OECD guideline study, to GLP, available.

Justification for selection of eye irritation endpoint:
Substance is corrosive to skin, thus no eye irritation study conducted.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

Corrosion to the skin was observed following 4 hours exposure, with observation up to 6 days. This satisfies the criteria for the Skin Corrosive subcategory 1C (applicable when responses occur after exposure between 1 and 4 hours and observations up to 14 days).

Skin corrosive substances shall be considered as leading to serious damage to the eyes (Category 1 - Irreversible effects on the eyes), in accordance with EU CLP Regulation (EC1272/2008, as amended).