7,7,9(or 7,9,9)-trimethyl-4,13-dioxo-3,14-dioxa-5,12-diazahexadecane-1,16-diyl bismethacrylate

Endpoint summary

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.