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Description of key information

There was evidence of corrosivity when tetrachloroauric(III) acid was applied to the skin of one rabbit using a 4-hour occluded patch. The study was performed in accordance with OECD test guideline with GLP. 
Eye irritation test was waived since the available information indicates that the criteria are met for classification as corrosive to the skin.
No data were identified relating to irritation to the respiratory tract. Given the result from the skin irritation study, tetrachloroauric acid is likely to cause respiratory irritation under physiological conditions.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation / corrosion, other
Remarks:
Although it was not the intention to demonstrate skin corrosion in this OECD404 study, the unexpected result fulfilled the endpoint criteria.
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19 - 24 March 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant, guideline test, available as an unpublished report. Reliable without restriction.
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
Species:
rabbit
Strain:
other: White Russian (Albino)
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: ASTA Medica AG, D-33790 Halle/Westfalen
- Age at study initiation: 8 months
- Weight at study initiation: 2.32 kg
- Fasting period before study: Approx. 16 hours prior to treatment
- Housing: Macrolon cages, type II. Individual caging.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):as libitum
- Acclimation period: The animals were kept at least one day under test conditions prior to administration of the test substance.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 - 20.0°C
- Humidity (%): 50-58%
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 6am - 6pm CET artificial lighting, 6pm - 6am CET darkness
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: no control animal: a similarly prepared patch without test substance on the other side of the animal was used as a control
Amount / concentration applied:
0.5g
Duration of treatment / exposure:
4 hours
Observation period:
Immediately after removal of the patch
Number of animals:
1
Details on study design:
TEST SITE
- Area of exposure: 6.25 cm2
- % coverage: Not calculated
- Type of wrap if used: Patch with two layers: Layer 1: Cellulose fabric coated with natural rubber, Layer 2: Synthetic film glue; Bandage: Acrylastic.


REMOVAL OF TEST SUBSTANCE
Animal was sacrificed immediately after removal of the patch


SCORING SYSTEM: Not used
Irritation parameter:
other: Yellow and black discoloration of the skin, depression and slight oedema
Remarks:
Severe diffuse coagulation necrosis of the skin at the application site and subcutis and cutaneous muscle. Severe focal deposition of black granular particles at these sites and at reticulin fibres and skeletal muscle was also found.
Basis:
animal #1
Time point:
other: Immediately on patch removal after 4 hours
Reversibility:
not specified
Remarks on result:
other: Any indication of irritation was marked by severe signs of corrosion to the skin
Remarks:
Due to the severity of the reaction, only one animal was exposed and assessed.
Irritant / corrosive response data:
Multiple severe signs of corrosion were observed after removal of the patch at 4 hours.
Skin at and around application site was discoloured. Depression of skin at and around application site was observed. Subcutis around application site exhibited slight edema.
After euthanization of the animal a microscopical examimation of the application site showed:
*Severe diffuse coagulation necrosis of the skin and subcutis
*Severe focal coagulation necrosis of the cutaneous muscle
*Severe focal deposition of black granular particles, predominately at the periphery of the coagulation necrosis and at reticulin fibres and skeletal muscle
*Minimal focal inflammatory cell infiltrates
Interpretation of results:
other: corrosive
Remarks:
Criteria used for interpretation of results: not specified
Conclusions:
Tetrachloroauric(III) acid was found to be corrosive to the skin of the rabbit.
Executive summary:

In a GLP compliant, guideline test, tetrachloroauric(III) acid was found to be corrosive to the skin of the rabbit.

Endpoint:
skin corrosion: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant, guideline test, available as an unpublished report. Reliable without restriction.
Qualifier:
according to guideline
Guideline:
OECD Guideline 435 (In Vitro Membrane Barrier Test Method for Skin Corrosion)
Deviations:
no
GLP compliance:
yes
Test system:
artificial membrane barrier model
Source species:
other: CORROSITEX Assay Kit (Corrosion Detection System (CDS) covered by a bio-barrier membrane)
Cell type:
other: Synthetic system
Cell source:
other: Synthetic system
Source strain:
other: Synthetic system
Details on animal used as source of test system:
Not applicable
Justification for test system used:
In order to replace in vivo testing for skin corrosion, validation studies on alternative in vitro methods were conducted by ICCVAM. One such alternative method was the In vitro Membrane Barrier Test (CORROSITEX (TM) Assay). It was oncluded that this assay could be used as part of a tiered testing strategy for the assessment of the dermal corrosion hazard potential of chemicals. In addition the method allows the subcategorisation of corrosive substances as permitted in the United Nations Globally Harmonised System of Classification and Labelling of Chemicals (GHS) and the assignment to EU Risk Phrases.
Details on test system:
BIOBARRIER preparation: At least 2 hours before test initiation, the dilutent was added to the matrix powder and heated to 68°C in a water bath under smooth agitation. After complete dissolution, the solution was allowed to sit for 5 minutes and 200 µL was pipetted into each membrane disc. The BIOBARRIERS were set on the tray and kept for at least 2 hours at 2-8°C.
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Amount/concentration applied:
Preparation of test item: 500 µL of the test item was applied, undiluted, directly atop the BIOBARRIER
Negative control: 500 µL citric acid (10%) in aqua dest.
Positive control: 1) 500 µL nitric acid (69%), 2) 500 µL phosphoric acid (85%)
Duration of treatment / exposure:
Exposure: Time was recorded from the addition of the test substance to the BIOBARRIER disc to observation of the reaction.
Observation: Time was recorded from the addition of the test substance to the BIOBARRIER disc to observation of the reaction
Qualifying test: 150 µL of the test substance was added to the Qualify test tube, shaken to allow dissolution and left to stand for 1 minute
Categorisation test: 150 µL test substance was added to two tubes and colour changes observed after shaking
Classification test: CDS vials 1-4 were warmed to room temperature (17-25°C) and one BIOBARRIER disc was added to the top of each vial with 500 µL test item applied evenly over the top. Time was recorded from the preparation of the individual vial to observation of the reaction.
Data analysis: The mean time for the four sample replicates to activate the CDS was calculated and used to assign the test substance to the appropriate packing group.
Number of replicates:
Replicates: 4 BIOBARRIERs for the test item, 1 BIOBARRIER for each of the positive (+1, +2), negative (-) and colour controls (C)
Species:
other:
Observation period:
.
Irritation / corrosion parameter:
penetration time (in minutes)
Value:
> 3.69 - < 5.11
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: Under the given test conditions, tetrachloroauric acid showed corrosive effects and is classified as "corrosive" category 1B (R34)
Other effects / acceptance of results:
Qualification test: The test substance was compatible with the CORROSITEX Assay
Categorisation test: An indistinct colour change was observed in categorisation tubes A and B and a pH test was used to confirm classification into category 1
Positive control: The times required to activate the CDS were 1.97 and 16.42 minutes for positive controls 1 and 2 respectively
Negative control: The time required to activate the CDS was 67.67 minutes
Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The mean time required to activate the corrosion detection system was 4.40 ± 0.71 minutes. Tetrachloroauric acid solution showed corrosive effects under the given test conditions and is classified as corrosive to skin category 1B (R34).
Executive summary:

Tetrachloroauric acid was tested in vitro for its corrosivity to skin according to OECD guideline 435 using a Corrosion Detection System covered by a bio-barrier membrane. The mean time to activate the corrosion detection system was 4.40 ± 0.71 minutes. Tetrachloroauric acid solution showed corrosive effects under the given test conditions and is classified as corrosive to skin category 1B (R34).

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 need not be conducted because the available information indicates that the criteria are met for classification as corrosive to the skin or irritating to eyes
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.

The 1993 GLP in vivo study for skin irritation showed that tetrachloroauric acid is corrosive to the skin. When applied to the shaved skin of one rabbit using a 4 -hour occluded patch the test substance caused corrosivity as defined by the clinical assessment of the skin injury. However, this result does not allow for accurate subcategory classification for skin corrosivity, hence, an in vitro skin corrosion assessment study was conducted (2013). In this study, the detection of skin tissue destruction after exposure times >3minutes and =/<1 hour defines the skin corrosion effect as Subcategory 1B. These skin corrosion studies indicate that the test substance would be irritant to eyes. The key and supporting skin irritation/corrosion studies are considered sufficient to meet the criteria for classification as skin corrosive and eye irritant under EC Regulation 1272/2008.

No data were identified relating to irritation to the respiratory tract. Given the result from the skin irritation study, tetrachloroauric acid is likely to cause respiratory irritation.


Effects on skin irritation/corrosion: corrosive

Justification for classification or non-classification

Acceptable in vivo and in vitro skin irritation tests gave results that meet the criteria for classification for skin corrosivity and eye irritation under EC Regulation 1272/2008 (Skin Corr. 1B H314: Causes severe skin burns). The eye irritation studies were waived on the basis of the skin corrosivity. Consequently, classification for eye irritation is based upon the perceived risk and is assigned Eye Damage 1 H318: Causes serious eye damage.