Registration Dossier

Administrative data

Description of key information

Skin irritation/corrosion: In a primary skin irritation/corrosion study in 1 male New Zealand White rabbit, performed according to OECD Guideline 404, EPA OPPTS 870.2500 and JMAFF Japanese Test Guideline, the test substance was observed to be corrosive to the skin (van Otterdijk, 2003).

Eye irritation test: According to the REACH Regulation (Annex VII column 2 adaptation), an eye irritation test does not need to be performed if the substance is corrosive to the skin.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2003-03 - 2003-04
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
- Name of test material (as cited in study report): XTJ 568
- Physical state: Clear colourless liquid
- Analytical purity: 97.8%
- Impurities (identity and concentrations): No data
- Purity test date: No data
- Lot/batch No.: 8191-34
- Expiration date of the lot/batch: 01-01-2004
- Stability under test conditions: no data
- Storage condition of test material: at room temperature in the dark
- Other: specific gravity: 0.94 g/cm3
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: at least 6 weeks old
- Weight at study initiation: at least 1.0 kg
- Housing: Animals were housed in controlled environment. Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 56 x 44 x 37.5 cm)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days before start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.9 - 21.7 °C
- Humidity (%): 49-76%
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 / 12
- Cleaning procedures in the room might have caused the temporary fluctuations above the optimal level of 70% for relative humidity. Based on laboratory historical data these conditions were considered not to have affected the study integrity
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:
3 min and 1 h
Observation period:
In the initially treated animal, the skin reactions of all visible treated sites were assessed immediately after removal of a dressing. The skin reactions on the 3-minute treated skin area were also assessed approximately 1 hour after exposure.
Number of animals:
1 male
Details on study design:
TEST SITE
- Area of exposure: clipped skin of the flanks
- % coverage: 150 cm2 (10 x 15 cm2)
- Type of wrap if used: Metalline patch of 2 x 3 cm; the patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage.

REMOVAL OF TEST SUBSTANCE
- The dressing was removed 3 minutes and 1 hour after application. The treated skin was cleaned with water.

SCORING SYSTEM:
Erythema and eschar formation:
No erythema: 0
Very slight erythema (barely perceptible): 1
Well-defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beet redness)*: 4
*: Where signs of necrosis or corrosion (injuries in depth) prevent erythema scoring, the maximum grade for erythema (=4) is given.

Oedema formation:
No oedema: 0
Very slight oedema (barely perceptible): 1
Slight oedema (edges of area well-defined by definite raising): 2
Moderate oedema (raised approximately 1 millimeter): 3
Severe oedema (raised more than 1 millimeter and extending beyond the area of exposure: 4
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
3 min exposure
Time point:
other: immediately after removal bandage
Score:
1
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
3 min exposure
Time point:
other: 1 h after removal bandage
Score:
2
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
3 min exposure
Time point:
other: immediately and 1 h after removal of dressing
Score:
0
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
1 h exposure (2 test sites)
Time point:
other: immediately after removal of dressing
Score:
4
Remarks on result:
other: Wound with serious exudate, grey discolouration, sign of necrosis
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
1 h exposure (2 test sites)
Time point:
other: immediately after removal bandage
Score:
2
Irritant / corrosive response data:
1-hour and intended 4-hours treatment site: wound with serious exudate
A 3-minute exposure to 0.5 mL of XTJ 568 resulted in well defined erythema in the treated skin-area. A 1-hour exposure resulted in severe erythema and slight oedema. In addition, gray discolouration of the treated skin (signs of necrosis) and a wound with serious exudate were seen on the 1-hour treated skin sites.

Colouring:
No staining of the treated skin by the test substance was observed

Other effects:
Toxicity/Mortality:
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.
Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Conclusions:
Evidence of full thickness destruction of the skin (wounds and gray discolouration of the skin) was observed immediately after a 1-hour exposure period, indicating that corrosion of the skin had occurred by dermal application of the substance to the intact rabbit skin. The substance is considered classified as corrosive to the skin (category 1B) according to CLP criteria.
Endpoint:
skin corrosion: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
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)
Endpoint conclusion
Endpoint conclusion:
no study available

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation/corrosion:

van Otterdijk (2003) performed a primary skin irritation/corrosion study in 1 male New Zealand White rabbit (semi-occlusive application). The study was carried out based on the guidelines described in: EC Commission Directive 92/69/EEC, B4, "Acute Toxicity - Skin irritation", OECD No. 404, "Acute Dermal Irritation/Corrosion" and US EPA OPPTS 870.2500, Acute Dermal Irritation and JMAFF, Japanese Test Guidelines.

Initially, one rabbit was exposed to three samples of 0.5 mL of the substance applied to separate skin-sites on intact, clipped skin using a semi-occlusive application. The exposure periods were 3 minutes and 1 hour, respectively. Based on the severity of the skin reactions, no further animals were exposed and the initially treated animal was sacrificed after a 1 -hour exposure period. A 3 -minute exposure to 0.5 mL of the substance resulted in well defined erythema in the treated skin area. A 1 -hour exposure resulted in severe erythema and slight oedema. In addition, gray discolouration of the treated skin (sign of necrosis) and a wound with serious exudate were seen on the 1 -hour treated skin sites. Evidence of full thickness destruction of the skin (wounds and gray discoloration of the skin) was observed immediately after a 1-hour exposure period, indicating that corrosion of the skin had occurred by dermal application of the substance to the intact rabbit skin.

Eye irritation:

According to the REACH Regulation (Annex VII column 2 adaptation), an eye irritation test does not need to be performed if the substance is corrosive to the skin.


Justification for classification or non-classification

Based on the available test results and according to the CLP Regulation, the substance should be classified as corrosive to the skin category 1B; H314 and as serious eye damaging category 1. This conclusion is in line with the RAC opinion proposing harmonised classification and labelling at EU level of the test substance, adopted 9 December 2016 (CLH-O-0000001412-86-132/F).