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Administrative data

Description of key information

Based on the available results from the read across studies, the test substance is considered to be corrosive to the skin and eyes.

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:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
From 23 February, 1988 to 8 March, 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
KL2 due to RA
Justification for type of information:
Refer to the Quaternary ammonium salts (QAS) category or section 13 of IUCLID for details on the category justification.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Mohican Valley Rabbitry; Loudonville, Ohio
- Age at study initiation: Young adult
- Weight at study initiation: 2,736 to 3,450 g at study initiation
- Housing: Individual suspended wire-mesh cages. The animals were maintained in accordance with the recommendations contained in the "guide for care and use of laboratory animals" NIH publication, No. 85023.
- Diet: Purina Certified Rabbit Chow #5322
- Water: Tap water
- Acclimation period: 7 d

ENVIRONMENTAL CONDITIONS
- Temperature : 71-74 °F
- Humidity (%): 50-74%
- Photoperiod (hrs dark / hrs light): 12 h light/12 h dark

IN-LIFE DATES: From: 23 February, 1988 to 8 March, 1988
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL/site
Duration of treatment / exposure:
4 h
Observation period:
14 d
Number of animals:
3 males and 3 females
Details on study design:
TEST SITE
0.5 mL dose was applied under secured 1 x 1 inch2 guaze patches that were overwrapped with a gauze binder secured with dermiform tape. Plastic restraint collars were applied and remained on the animals for the duration of the exposure period.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: At the end of 4 h, the collars and bandages were removed and the sites wiped with wet disposable paper towels.

SCORING SYSTEM: Draize
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
5.6
Max. score:
8
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: severely irritating (due to not completely reversible reactions (moderate irritation was still present in one rabbit); in addition desquamation was noted on all sites late in the study period and fissuring was present on two sites
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
2.8
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
2.2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 d
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 3
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 2.6
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
ca. 3
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
ca. 3
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
ca. 3
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 3.6
Max. score:
4
Reversibility:
not fully reversible within: 14 d
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 1.6
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of mild irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 2
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
ca. 3
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
ca. 3.6
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of moderate irritation
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
ca. 2.3
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of moderate irritation
Irritant / corrosive response data:
Average erythema score for all animals at 24h: 3; 48h: 3; 72h: 2.8
Average edema score for all animals at 24h: 3.2; 48h: 2.8; 72h: 2.2
Reversibility: Yes, the highest levels of irritation occurred two to three days after dosing and irritation subsequently decreased although moderate reactions still persisted in one animal after study Day 12.
The test substance induced moderate erythema and moderate to severe oedema on all sites. Irritation decreased as the study progressed, however, moderate irritation was present in one rabbit (score: erythema:2; edema:1) through study Day 11.
Other effects:
Desquamation was noted on all sites late in the study period and fissuring was present on two sites.

Mortality: One rabbit was sacrificed in extremis on Day 3 due to broken back.

Body weight: No remarkable changes occurred.

Result details

Table 1:                           Table for skin irritation study

score (average animals investigated)

time

Erythema

Edema

average score
Draize scores
(0 to maximum 4)

< 1 hr After exposure

2.6

1.5

24 h

3

3.2

48 h

3

2.8

72 h

2.8

2.2

other times

State time

 

 

average score

24h, 48h, 72h

3.0

2.7

reversibility: *

n.c

n.c

Average time for reversibility

 

 

*    c :    completely reversible
  n c :    not completely reversible
     n :    not reversible

Interpretation of results:
other: Category 1C (corrosive) based on CLP criteria
Conclusions:
Based on the results of the read across study, the test substance is considered to be corrosive.
Executive summary:

A study was conducted to determine the skin irritation potential of the read across substance, Coco TMAC (33% active in water), in New Zealand White rabbits according to OECD 404 Guideline, in compliance with GLP. Six animals were treated with 0.5 mL undiluted read across substance (33%) in a semi-occlusive patch (1” X 1” gauze) that was overwrapped with a gauze binder and secured with dermiform tape. Plastic restraint collars were applied and remained on the animals for the duration of the 4 h exposure period, after which the tape and read across substance were removed. The Draize classification scoring criteria was used to evaluate the irritation potential. Application sites were observed for erythema and oedema at 4, 24, 48 and 72 h after exposure and then daily up to 14 d. The read across substance induced moderate erythema and moderate to severe edema on all sites. Remission of irritation signs occurred as the study progressed, however, moderate irritation was still present in one rabbit after study Day 12 (erythema: 2 ‘slight’; edema:1 ‘barely perceptible’). In addition, desquamation was noted on all sites late in the study period and fissuring was present on two sites. The Primary Irritation Index was calculated to be 5.6 (indicative of moderate irritation). Under the study conditions, due to persistence of irritation reactions in one animal as well as desquamation on all sites and fissuring on 2 sites, the read across substance is considered to be severely irritating. Under the study conditions, the read across substance (containing 33% a.i.) was found to be severely irritating to rabbit skin; therefore, 100% Coco TMAC can be considered to be corrosive (Naas, 1988). Based on the results of the read across, a similar corrosive potential is expected for the test substance.

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
Reason / purpose:
data waiving: supporting information
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
From 22 February 1988 to 14 March, 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
KL2 due to RA
Justification for type of information:
Refer to the Quaternary ammonium salts (QAS) category or section 13 of IUCLID for details on the category justification.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Mohican Valley Rabbitry, Loudonville, Ohio
- Age at study initiation: Young adult
- Weight at study initiation: 2,634 to 3,104 g at study initiation
- Housing: Individual suspended wire-mesh cages. The animals were maintained in accordance with the recommendations contained in the "guide for care and use of laboratory animals" NIH publication, No. 8502
- Diet: Purina Certified Rabbit Chow #5322
- Water: Tap water
- Acclimation period: 7 d

ENVIRONMENTAL CONDITIONS
- Temperature : 67-74 °F
- Humidity (%): 40-74%
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From 23 February, 1988 to 8 March, 1988
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
Single treatment
Observation period (in vivo):
Both eyes were examined at approximately 1, 24, 48 and 72 h after dosing and at 96 h and 7, 14 and 21 d. In addition, both eyes of all rabbits were further examined at 72 h and 7, 14 and 21 d with sodium fluorescein and ultraviolet light.

Number of animals or in vitro replicates:
5 males and 4 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Out of the 9 animals, the eye of the three rabbits were washed with 120 mL of lukewarm tap water for approximately 1 min.
- Time after start of exposure: 30 sec after dosing

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: Sodium fluorescein and ultraviolet light
Irritation parameter:
other: Maximum average score (M.A.S)
Basis:
mean
Time point:
other: 14 d
Score:
96.8
Max. score:
110
Reversibility:
not fully reversible within: 21 d
Remarks on result:
other: This value is for unwashed group
Irritation parameter:
other: Maximum average score
Basis:
mean
Time point:
other: 72 h
Score:
69.7
Max. score:
110
Reversibility:
not fully reversible within: 21 d
Remarks on result:
other: This value is for washed group
Irritation parameter:
other: Maximum average score
Basis:
mean
Time point:
other: 96 h
Score:
69.7
Max. score:
110
Reversibility:
not fully reversible within: 21 d
Remarks on result:
other: This value is for washed group
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
2.5
Max. score:
4
Reversibility:
not fully reversible within: 21 d
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 1.03
Max. score:
4
Reversibility:
not fully reversible within: 21 d
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 2.3
Max. score:
4
Reversibility:
not fully reversible within: 21 d
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
(discharge)
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 2.56
Max. score:
4
Reversibility:
not fully reversible within: 21 d
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 3.92
Max. score:
4
Reversibility:
not fully reversible within: 21 d
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
The test substance was maximally irritating for the unwashed group and extremely irritating for the washed group.
Other effects:
Purulent discharge, clear discharge, petite hemorrhage, blanching, corneal epithelial damage, corneal neovascularization, sodium fluorescein stain retention.

Table 1.                           Results of eye irritation study

 

 

Cornea

Iris

Conjunctiva

redness

chemosis

Score (average of animals investigated)

0 to 4

0 to 2

0 to 3

0 to4

60 min

3.0

1

1

4

24 h

2.8

1

1.7

4

48 h

2.8

1

2.3

4

72 h

2.8

1

2.8

4

21 days

4

0.3

1.8

2.5

Average 24h, 48h, 72h

2.8

1

2.3

4

Area effected

> 75%

Maximum average score (including area affected, max 110)

96.8 on day 14

Reversibility*

n

Average time for reversion

 

Give method of calculation maximum average score.

*          c :       completely reversible
           n c :    not completely reversible
           n :       not reversible

Cornea:   (opacity * area) * 5
Iris:
          Iris * 5
Conjunct.: (redness+chemosis+discharge)*2

Max. score: 80 + 10 + 20 = 110

Interpretation of results:
other: Category 1 (irreversible effects on the eye) based on CLP criteria
Conclusions:
Based on the results of the read across study, the test substance is considered to cause irreversible effects on the eye.
Executive summary:

A study was conducted to determine the skin irritation potential of the read across substance, Coco TMAC (33% active), in New Zealand White rabbits according to OECD 405 Guideline, in compliance with GLP. Nine rabbits received 0.1 mL of undiluted solution in one eye. The other eye remained untreated. The eyelids were held close for approximately 1 second after instillation. The eyes of three rabbits were washed for approximately 1 minute with 120 mL of lukewarm tap water commencing approximately 30 seconds after dosing. Both eyes were examined at for ocular irritation in accordance with the method of Draize approximately 1, 24, 48 and 72 h after dosing and at 96 h and 7, 14 and 21 d. In addition, both eyes of all rabbits were further examined at 72 h and 7, 14 and 21 d with sodium fluorescein and ultraviolet light. Body weights were obtained and recorded on study day 0 (initiation) and at termination (Day 21). Based on the data obtained, the Maximum Average Scores (according to Kay and Calandra) for the read across substance were calculated to be 96.8 (extremely irritating) at 14 d for the unwashed group and 69.7 (severely irritating) at both 72 and 96 h for the washed group. Purulent discharge, clear discharge, petite haemorrhage, blanching, corneal epithelial damage and peeling, corneal neovascularisation, Sodium fluoresceinstain retention, and vascularised granulation scar tissue was observed in all 6 animals. Same effects were observed in the washed group, except for vascularised granulation scar tissue. There were no deaths or remarkable body weight changes during the study period. Under the study conditions, the read across substance is considered to cause irreversible effects on the eye (Naas, 1988). Based on the results of the read across study, a similar corrosive potential can be expected for the test substance.

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Reason / purpose:
data waiving: supporting information
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin

A study was conducted to determine the skin irritation potential of the read across substance, Coco TMAC (33% active in water), in New Zealand White rabbits according to OECD 404 Guideline, in compliance with GLP. Six animals were treated with 0.5 mL undiluted read across substance (33%) in a semi-occlusive patch (1” X 1” gauze) that was overwrapped with a gauze binder and secured with dermiform tape. Plastic restraint collars were applied and remained on the animals for the duration of the 4 h exposure period, after which the tape and read across substance were removed. The Draize classification scoring criteria was used to evaluate the irritation potential. Application sites were observed for erythema and oedema at 4, 24, 48 and 72 h after exposure and then daily up to 14 d. The read across substance induced moderate erythema and moderate to severe edema on all sites. Remission of irritation signs occurred as the study progressed, however, moderate irritation was still present in one rabbit after study Day 12 (erythema: 2 ‘slight’; edema:1 ‘barely perceptible’). In addition, desquamation was noted on all sites late in the study period and fissuring was present on two sites. The Primary Irritation Index was calculated to be 5.6 (indicative of moderate irritation). Under the study conditions, due to persistence of irritation reactions in one animal as well as desquamation on all sites and fissuring on 2 sites, the read across substance is considered to be severely irritating. Under the study conditions, the read across substance (containing 33% a.i.) was found to be severely irritating to rabbit skin; therefore, 100% Coco TMAC can be considered to be corrosive (Naas, 1988). Based on the results of the read across, a similar corrosive potential is expected for the test substance.

Eye

A study was conducted to determine the skin irritation potential of the read across substance, Coco TMAC (33% active), in New Zealand White rabbits according to OECD 405 Guideline, in compliance with GLP. Nine rabbits received 0.1 mL of undiluted solution in one eye. The other eye remained untreated. The eyelids were held close for approximately 1 second after instillation. The eyes of three rabbits were washed for approximately 1 minute with 120 mL of lukewarm tap water commencing approximately 30 seconds after dosing. Both eyes were examined at for ocular irritation in accordance with the method of Draize approximately 1, 24, 48 and 72 h after dosing and at 96 h and 7, 14 and 21 d. In addition, both eyes of all rabbits were further examined at 72 h and 7, 14 and 21 d with sodium fluorescein and ultraviolet light. Body weights were obtained and recorded on study day 0 (initiation) and at termination (Day 21). Based on the data obtained, the Maximum Average Scores (according to Kay and Calandra) for the read across substance were calculated to be 96.8 (extremely irritating) at 14 d for the unwashed group and 69.7 (severely irritating) at both 72 and 96 h for the washed group. Purulent discharge, clear discharge, petite haemorrhage, blanching, corneal epithelial damage and peeling, corneal neovascularisation, Sodium fluoresceinstain retention, and vascularised granulation scar tissue was observed in all 6 animals. Same effects were observed in the washed group, except for vascularised granulation scar tissue. There were no deaths or remarkable body weight changes during the study period. Under the study conditions, the read across substance is considered to cause irreversible effects on the eye (Naas, 1988). Based on the results of the read across study, a similar corrosive potential can be expected for the test substance.


Justification for classification or non-classification

Based on the results of the read across in vivo skin and eye irritation studies, the undiluted test substance warrants a corrosive, ‘Skin Corr. 1C; H314: Causes severe skin burns and eye damage’ as well as serious eye damage, ‘Eye dam. 1; H31: Causes serious eye damage’ classification according to the EU CLP criteria (Regulation EC 1272/2008). Labelling for this endpoint is covered by the above classifications for skin effects.