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Description of key information

Skin, rabbit (OECD 404): not irritating

Eye, rabbit (OECD 405): not irritating

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:
19 - 22 Jun 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted in 2015
Deviations:
yes
Remarks:
an occlusive dressing was used
Qualifier:
according to guideline
Guideline:
other: EEC Directive 79/831, Annex V, Part B: Methods for the determination of toxicity; 4.1.5. Acute toxicity "Skin Irritation"
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
other: New Zealand White, KFM
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, Fuellinsdorf, Switzerland
- Age at study initiation: 13 - 14 weeks
- Weight at study initiation: 2.2 - 2.3 kg
- Housing: individually in stainless steel cages equipped with automatic cleaning and drinking system
- Diet: pelleted standard Kliba 341, batch 95/84 rabbit maintenance diet (Klingentalmuehle AG, Switzerland), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 19 Jun 1984 To: 22 Jun 1984
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
72 h
Reading time points: 1, 24, 48 and 72 h.
Number of animals:
1 male
2 females
Details on study design:
TEST SITE
- Area of exposure: approximately 3 cm²
- Type of wrap if used: the treaty skin was covered with a 3 x 3 cm patch of surgical gauze, which was covered with aluminium foil and an occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the skin was rinsed with lukewarm tap water.
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: mean after 24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: mean after 24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritant / corrosive response data:
No skin irritation effects were observed in any of the animals at any reading time point. All the erythema and edema scores were 0 at all reading time points.
Other effects:
No mortality occurred during the study period, and no effect on body weight was noted.
Interpretation of results:
other: CLP/GHS criteria not met; no classification required according to Regulation (EC) No. 1272/2008
Conclusions:
CLP: not classified
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:
key study
Study period:
19 - 22 Jun 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Guideline study with acceptable restrictions. No topical anasthetic was applied to the eye prior to test substance instillation.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted Oct 2012
Deviations:
yes
Remarks:
no topical anasthetic was applied to the eye prior to test substance instillation
Qualifier:
according to guideline
Guideline:
other: EEC Directive 79/831, Annex V, Part B: Methods for the determination of toxicity; 4.1.6 Acute toxicity 'Eye irritation'
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
other: New Zealand White, KFM
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, Fuellinsdorf, Switzerland
- Age at study initiation: 13 - 14 weeks
- Weight at study initiation: 2.2 - 2.3 kg
- Housing: individually in stainless steel cages equipped with automatic cleaning and drinking system
- Diet: pelleted standard Kliba 341, batch 95/84 rabbit maintenance diet (Klingentalmuehle AG, Switzerland), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 19 Jun 1984 To: 22 Jun 1984
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
single application without washing
Observation period (in vivo):
72 h
Reading time points: 1, 24, 48 and 72 h
Number of animals or in vitro replicates:
2 males, 1 female
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): the eyes were not rinsed after instillation

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: hand-slit lamp and diagnostics lamp
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility: not applicable
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: reversibility: not applicable
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritant / corrosive response data:
At the 1-h reading time point 3/3 animals had discharge from the treated eye. No corneal effect or iritis, and no conjunctivae or chemosis was noted at any time point in any animal. All the scores were 0 for 3/3 rabbits at all reading time points.
Other effects:
No mortality occurred and no treatment-related clinical signs were reported. The body weight changes were within the normal range for males and females during the study period.
Interpretation of results:
other: CLP/GHS criteria not met; no classification required according to Regulation (EC) No. 1272/2008
Conclusions:
CLP: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation/corrosion

A skin irritation study was conducted with Reaction mass of 7,7,9-trimethyl-4,13-dioxo-3,14-dioxa-5,12-diazahexadecane-1,16-diylbismethacrylate and 7,9,9-trimethyl-4,13-dioxo-3,14-dioxa-5,12-diazahexadecane-1,16-diylbismethacrylate (CAS 72869-86-4) following a protocol similar to OECD guideline 404 and under GLP conditions (Ullmann, 1984). The shaved skin of 3 New Zealand White, KFM rabbits was exposed to 0.5 mL undiluted test substance for 4 h under occlusive conditions. The skin irritation effects were evaluated 1, 24, 48 and 72 h after patch removal. No skin irritation effects were observed in any of the animals at any reading time point. All the erythema and edema scores were 0 at all reading time points. The test substance is not considered to be irritating to the skin.

An acute skin irritation study was performed with Reaction mass of 7,7,9-trimethyl-4,13-dioxo-3,14-dioxa-5,12-diazahexadecane-1,16-diylbismethacrylate and 7,9,9-trimethyl-4,13-dioxo-3,14-dioxa-5,12-diazahexadecane-1,16-diylbismethacrylate (CAS 72869-86-4) following the Draize testing method (Draize JH et al., J. Pharm. Exp. Ther. 82: 377-390, 1944) as prescribed by the FDA (in The Federal Register 38 No.187 §15000.42, USA) (Sterner, 1977). The shaved skin of 6 New Zealand White rabbits was exposed to 0.5 mL undiluted test substance for 24 hs under occlusive conditions. The skin irritation effects were evaluated 0 and 48 h after patch removal (24 and 72 h after application). Twenty-four h after application, 5/6 rabbits exhibited very slight to well-defined erythema (score 1 - 2), while 1/6 rabbits had no erythema. 2/6 animals exhibited very slight edema (score 1) directly after patch removal. The erythema and edema had cleared completely in 6/6 rabbits within 72 h after application. Based on the results and considering the long exposure time using an occlusive dressing, the test substance showed low skin irritation potential. Therefore, the test substance is not considered to be skin irritating under the conditions of the study.

Eye irritation/corrosion

An acute eye irritation study was conducted with Reaction mass of 7,7,9-trimethyl-4,13-dioxo-3,14-dioxa-5,12-diazahexadecane-1,16-diylbismethacrylate and 7,9,9-trimethyl-4,13-dioxo-3,14-dioxa-5,12-diazahexadecane-1,16-diylbismethacrylate (CAS 72869-86-4) according to OECD guideline 405 and under GLP conditions (Ullmann, 1984). 0.1 mL of the undiluted test substance was instilled into one eye of 3 New Zealand White, KFM rabbits. The animals were observed for 72 h and eye irritation scoring was performed 1, 24, 48 and 72 h after instillation. At the 1-h reading time point 3/3 animals had discharge from the treated eye. No corneal effect or iritis, and no conjunctivae or chemosis was noted at any time point in any animal. All the scores were 0 for 3/3 rabbits at all reading time points. No mortality occurred and no treatment-related clinical signs were reported. The body weight changes were within the normal range for males and females during the study period. The test substance is not considered to be irritating to the eye.

Justification for classification or non-classification

The available data on skin and eye irritation/corrosion do not meet the classification criteria according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.