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Description of key information

The available skin and eye irritation studies with rabbits show that the test substance is corrosive to the skin and eyes.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non GLP, non guideline study. Available as unpublished report. Restrictions in design and reporting but adequate for assessment.
Principles of method if other than guideline:
0.5 mL of the test substance was applied to the skin of New Zealand White rabbits and covered with a patch for 4 hours. After exposure, the site was washed with water. Observations were made at removal of the test patch and at 24 and 48 hours.
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Housing: Stainless steel with elevated wire mesh flooring; 1 rabbit/cage
- Diet: Wayne 15% Rabbit Ration, ad libitum
- Water: Tap water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15.6 - 23.9
- Humidity (%): 40-45
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
48 hours
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: approximately one square inch.
- Type of wrap if used: Surgical gauze patches measuring not less than 1" x 1" and two single layers thick were placed over the treated area and impervious material was wrapped snugly around the trunk of the animal to hold the patch in place.

REMOVAL OF TEST SUBSTANCE
- Washing: yes, with water
- Time after start of exposure: 48 hours

SCORING SYSTEM:
Corrosion was considered to have resulted if the material in contact with the rabbit skin had caused destruction or irreversible alteration of the tissue. Tissue destruction was considered to have occurred if, at any of the readings, there was ulceration or necrosis. Tissue destruction was considered to have occurred if merely sloughing of the epidermis, erythema, edema or fissuring was evident. Observations of skin irritation, if any, encountered during testing of the material were noted.
Remarks on result:
other: See "Irritant/corrosive response data"
Irritant / corrosive response data:
- 4 hours after exposure: Animal #1, 2, 3, 4 and 6 showed severe erythema, moderate edema and corrosion to the skin. Animal 5 showed slight erythema, moderate edema and no corrosion to the skin.
- 24 and 48 hours after exposure: Animal #1, 2 and 3 showed severe erythema, very slight edema and corrosion to the skin. Animal #4, 5 and 6 showed severe erythema, corrosion to the skin but no edema was observed.
Interpretation of results:
corrosive
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non GLP, non guideline study. Available as unpublished report. Restrictions in design and reporting but adequate for assessment.
Principles of method if other than guideline:
To assess the eye irritating potential of the test substance the undiluted compound was applied to the eye of a rabbit. The test was performed with and without washing of the eye following exposure.
GLP compliance:
no
Species:
rabbit
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: yes
Remarks on result:
other: See "Irritant/corrosive response data"
Irritant / corrosive response data:
Washed and unwashed: Slight pain upon direct contact followed by severe conjunctival and corneal injury resulting in permanent impairment of vision and possibly total loss of sight. Corneal injury was apparent immediately after contact.
Interpretation of results:
corrosive
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

SKIN IRRITATION:

In a skin irritation corrosion study (TSCATOTS0206641_1983), 0.5 mL of the test substance was applied to the skin of 6 New Zealand White rabbits and covered with a patch for 4 hours. After exposure, the site was washed with water. Observations were made at removal of the test patch and at 24 and 48 hours. After 24 and 48 hours after exposure, three animals showed severe erythema, very slight edema and corrosion to the skin. The other animals showed severe erythema, corrosion to the skin but no edema was observed.

In another study (TSCATOTS0206650_1964), undiluted test material was applied to the skin of rabbits. Animals were exposed for 1, 5, and 15 minutes followed by an one week observation period. One minute exposure resulted in slight hyperemia after one minute. No irritation was observed the next day or a week later. Five minute exposure resulted in moderate hyperemia observed after two minutes and five minutes and the next day. The skin was normal after one week. Fifteen minute exposure resulted in moderate hyperemia observed after two minutes and moderate burn after fifteen minutes. This burn appeared to be severe with severe hyperemia one day later. Severe scab remained after six days. The same study report also reported another test. The test substances was applied undiluted to the intact or abraded skin of the rabbit followed by a 21 -day obervation period. The intact skin test resulted in a severe burn accompanied by severe hyperemia and moderate edema after one application. A severe scar with moderate scab remained until day 21.

Duterte-Catella (1989) published a skin irritation/corrosion test. The amount of the test substance applied and duration of exposure were not available. Animals were sacrificed after 7 days and 14 days. Erythema and oedema were moderate to severe. Necrosis was observed in 2 rabbits. No regeneration occurred after 72 h. Histopathological examinations revealed ulceration and necrosis. Leucocyte infiltration were discrete on the 7th day and cicatrisation already well-established with persistence of hair follicles. The authors concluded the test substance to be corrosive and necrotizing for the skin.

Myers and Ballantyne (1997) published a study in which the irritation/ corrosive potential of the test substance was evaluated by applying 0.01 mL of the test substance to the clipped skin of groups of 5 rabbits for 30 minutes. The undiluted test substance was also tested on occluded rabbit skin (0.5 mL, 4-h). The open exposure test (30 minutes) resulted in moderate capillary injection and the 4 hour occluded test resulted in necrosis.

EYE IRRITATION

In an eye irritation corrosion study (TSCATOTS0206650_1964) the undiluted test substance was applied to the eye of a rabbit. The test was performed with and without washing of the eye following exposure. Exposure (washed and unwashed) resulted in slight pain upon direct contact followed by severe conjunctival and corneal injury resulting in permanent impairment of vision and possibly total loss of sight. Corneal injury was apparent immediately after contact.

Duterte-Catella (1989) published an eye irritation/corrosion test. In addition to the eye observations for the determination of Ocular irritation indices, animals were sacrificed after 7 days and 14 days. The observed eye irritation was severe. Histopathological examinations after 7 days revealed acute lesions of keratitis consisting in abrasion of the anterior epithelium of the cornea. Fibrillary oedematous dissociation of the lamellae leading to a 3- to 4-fold increase in thickness and cellular inflammatory infiltration were also observed. After 14 days, oedematous lesions as well as cellular infiltration persisted in most animals. Cicatrisation took place on a more or less important surface of the anterior epithelium. In a few animals, neo-capillaries invaded the stroma.

Myers and Ballantyne (1997) published a report in which the eye irritating potential of the test substance is assessed. 0.005 mL undiluted material, 0.5 mL (15% in water) and 0.5 mL (5% in water) was placed directly on the cornea. After 18-24 hour, the treated eyes were washed with water. Eyes were examined for ocular and periocular injury and/or inflammation. Exposure of the eye to the test substance resulted in severe corneal opacity and iritis (0.005 mL undiluted test substance), moderate corneal opacity and iritis (0.5 mL 15% in water). No effects were observed after application of 0.5 mL (5% in water). It should be note that the appropriate testing dose according to OECD guideline 405 0.1 mL is instead of the 0.005 mL (factor 20) used in this study.


Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

Despite the fact that most available skin irritation/corrosion studies were performed under occlusive conditions, based on the severity of the results, the test substance has to has to be classified as Skin corrosive: Cat 1C: H314: Causes severe skin burns and eye damage in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008 and C: R34: Causes burns in accordance with Directive 67/548/EEC (DSD).

Based on the corrosive eye effects observed the test substance has to be classified as Eye damage 1: H318: Causes serious eye damage in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008 and Xi: R41: Risk of serious damage to eyes in accordance with Directive 67/548/EEC (DSD).