Registration Dossier

Administrative data

Description of key information

Skin irritation (OECD TG 404): not irritating

Eye irritation (similat to OECD TG 405): severely eye damaging

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: well-documented, guideline-conform study report
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Lot/batch No.of test material: WF 4746

Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
Acclimatization period: at least 8 days before study start
Mean body weight: male 3.18 kg, females 2.92 kg
Singly housing in stainless steel wire mesh cages (floor area 40 x 51 cm).
The animals were identified via ear tattoo.
They were housed in fully air-conditioned rooms with a room temperature of 20 - 24°C and a relative humidity of 30 - 70%. The day/night rhythm was 12 h light and 12 h darkness.
The animals were offered a standardized animal laboratory diet (about 130 g/animal/day) as well as tap water (about 250 ml/animal/day).
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin of the animals
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
4 hours
Observation period:
30 - 60 min after removal of the test patches and 24 h, 48 h, 72 h after the beginning of the application
Number of animals:
3
Details on study design:
Clipping of the fur at least 15 hours before study start.
Application area: 2.5 x 2.5 cm
Application site: upper third of the back or flanks
Removal of the test substance at the end of the application period with Lutrol and Lutrol/water (1:1).
Readings: 30 - 60 minutes after removal of the test patches and 24 h, 48 h and 72 h after beginning of application.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 - 72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 - 72 h
Score:
0
Max. score:
0
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
purity of the test substance not specified
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Lot/batch No.of test material: C-001 388
- Trimethylolpropane tris (3-azirinyl) propanoate (CAS# 52234-82-9); (Paradox ID:A-11/08/91:01101)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: L.I.T. Laboratory Animals, Santa Clara, California
- Weight at study initiation: 2.5 - 3.5 kg
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): undiluted
Duration of treatment / exposure:
30 sec, 5 min, > 5 min (substance was not removed from the eye)
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
9 (in 3 rabbits the test material was washed off 30 sec after instillation, in 3 others the material was washed from the eye 5 min after Instillation and in the last 3, the compound was not washed from the eye.
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): in 3 rabbits the test material was washed off 30 sec after instillation, in 3 others the material was washed from the eye 5 min after Instillation and in the last 3, the compound was not washed from the eye

SCORING SYSTEM: The grading system was taken from the Draize Test.
Remarks on result:
other: eyes were so severly damaged that scoring was not possible
Irritant / corrosive response data:
The eyes of all rabbits treated with the test substance, regardless of the washing conditions, were so severely damaged by the reading at 1 hour that scoring corneal and iris tissue was impossible. Maximum scores were recorded for conjunctival tissue 1, 4, 24, and 72 hours after compound treatment. Bleeding from the eyes of several rabbits was observed at 72 hours.
Other effects:
The observations were not continued beyond 72 hours, and all rabbits were sacrificed at that time.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
The test substance is totally corrosive to the rabbit eye, even if it is washed out within 30 seconds of instillation.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation/corrosion:

In a skin irritation study according to OECD Guideline 404, 0.5 mL of the test substance were applied to the back (fur clipped at least 15 h before application of the test substance) of one male and 2 female White Vienna rabbits to an area of 2.5 x 2.5 cm. As negative control untreated skin sites of the same animal were used. After 4 h with semi-occlusive coverage, the substance was removed with Lutrol and Lutrol/water (1:1). Skin reactions were assessed 30 - 60 minutes after removal of the patch and 24, 48 and 72 h after the beginning of application. After patch removal very slight erythema were recorded in 2 of 3 animals (intact skin), which were fully reversible within 24 hours. Therefore, the test substance was not irritant under these test conditions.

Eye irritation:

In an eye irritation study, 0.1 mL of the substance was instilled into the right eye of 9 New Zealand White rabbits. The left eye served as the untreated control. In three rabbits, the test substance was washed from the eye 30 seconds after instillation; in three others, the material was washed from the eye 5 minutes after instillation; and in the last three, the compound was not washed from the eye. Each eye was graded for ocular lesions 1, 4, 24, and 72 hours after instillation of the test substance. The grading system was taken from the Draize Test.

Moderate-to-severe lesions of the cornea, iris, and conjunctivae were seen in all rabbits treated with the test substance, regardless of  wash treatment. Many corneal and iris reactions were difficult to score during the first few days due to extreme swelling of conjunctivae, resulting in closure of the eyelids. Generally, however, corneal opacity occurred within 24 hours. At 7 days after treatment, all 9 treated eyes had some degree of opacity over most or all of the corneal area. The density of these lesions ranged from translucent to opaque, with the worst cases appearing in the 5-minute wash group. Irises were also severely affected - two each in the 5-minute and no-wash groups showed no reaction to light. The remaining eyes in all groups had hemorrhaged irises. Conjunctival swelling, redness, and discharge were still extremely pronounced on Day 7.

The decision was made to sacrifice the rabbits on Day 7 since it appeared that healing, with a return to normal sight, was highly unlikely.

The test substance is considered to be a severe irritant to the rabbit eye.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for skin irritation, but has to be classified for causing severe eye damage (Cat. 1) under Regulation (EC) No. 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.

The classification as severely eye damaging is consistant with the harmonised classification and labelling (CLP00).