Quaternary ammonium compounds, coco alkyltrimethyl, chlorides

Endpoint summary

Description of key information

Based on the resultes of in vivo irritation studies, the test substance is considered to be  corrosive to skin and as well as eyes. 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: 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 for cross-reference:

data waiving: supporting information

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 23 February, 1988 to 8 March, 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system 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:

ca. 2.8

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

mean

Time point:

72 h

Score:

ca. 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:

ca. 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:

Under the study conditions, the test substance (containing 33% a.i.) was found to be severly irritating to rabbit skin; therefore, 100% Coco TMAC can be considered to be corrosive.

Executive summary:

A study was conducted to determine the skin irritation potential of the test 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 test 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 test 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 test 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 test substance is considered to be severely irritating. Under the study conditions, the test substance (containing 33% a.i.) was found to be severly irritating to rabbit skin; therefore, 100% Coco TMAC can be considered to be corrosive (Naas, 1988).

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

From December 1980 to June 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

other: Fed. Reg. 37 (244), 27635, 1972 and Draize test (1944)

Deviations:

yes

Remarks:

observations for 7 days instead of 14; 6 animals rather than 3 animals used, intact and abraded skin; occlusive rather than semi-occlusive application

Principles of method if other than guideline:

When the test substance appeared to be corrosive when applied onto the skin for 4 h, the test substance was also examined in a 2nd test following application for 1 h. Similarly, when corrosive for 1 h, the test substance was also examined in a 3rd test for 3 minutes.

GLP compliance:

no

Remarks:

pre-GLP

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

1 and 4 h

Observation period:

7 d

Number of animals:

6

Irritation parameter:

erythema score

Basis:

mean

Time point:

48 h

Score:

4

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: moderate incrustation and decreased hair growth

Irritation parameter:

edema score

Basis:

mean

Time point:

48 h

Score:

1.83

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: moderate incrustation and decreased hair growth

Other effects:

After 4 h: very slight erythema, very slight ischemia, and very slight oedema
After 2 d: distinct ischemia and very slight

Summary of dermal lesions (following 4-h application)

Animal no.	Effect	Hour	Days after application					Mean score erythema (48 h)	Mean score oedema (48 h)
		1	1	2	3	7	14
9948	Erythema/ eschar Oedema	4 2	- -	4 2	- -	- -	- -	4	2
9949	Erythema/ eschar Oedema	4 1	- -	4 2	- -	- -	- -	4	2
9950	Erythema/ eschar Oedema	4 1	- -	4 2	- -	- -	- -	4	2
9951	Erythema/ eschar Oedema	2 1	- -	4 1	- -	- -	- -	4	1
9952	Erythema/ eschar Oedema	4 2	- -	4 2	- -	- -	- -	4	2
9953	Erythema/ eschar Oedema	4 1	- -	4 2	- -	- -	- -	4	2
Mean all animals								4	1.83

Fa = abnormal fur growth; Fr = reduced fur growth; d = desquamation; t = thickening of skin

Interpretation of results:

other: Category 1C (corrosive) based on CLP criteria

Conclusions:

Under study conditions, the test substance was considered to be skin corrosive.

Executive summary:

A study was conducted to assess the skin irritation potential of the test substance, Coco TMAC (50% active) in New Zealand White rabbits according to USFDA (Fed. Reg. 37 (244), 27635, 1972) and draize test. A single 4 h, occluded application of the undiluted test substance to the intact skin of six rabbits produced distinct ischemia and very slight to slight oedema after 2 d. After 1 week, moderate incrustation and decreased hair growth were seen. No further observations were made. About similar observations were made using a 1 h exposure period. It was concluded by the author of the report that a 4 h exposure induced corrosive effects and a 1 h exposure did not. Under study conditions, the test substance was considered to be corrosive to the skin of rabbits (Beek, 1981).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Reference 1

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 for cross-reference:

data waiving: supporting information

Reason / purpose for cross-reference:

data waiving: supporting information

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 22 February 1988 to 14 March, 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

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:

ca. 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:

Under the study conditions, 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 test 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 test 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 test substance is considered to cause irreversible effects on the eye (Naas, 1988).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

Study 1: A study was conducted to determine the skin irritation potential of the test substance, TMAC C (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 test 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 test 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 test 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 test substance is considered to be severely irritating.Under the study conditions, the test substance (containing 33% a.i.) was found to be severly irritating to rabbit skin (Naas, 1988). Considering the results obtained with the test substance containing 33% of the a.i., it is proposed that 100% TMAC C can be considered to be corrosive to rabbit skin.

Study 2: A study was conducted to assess the skin irritation potential of the test substance, TMAC C (50% active) in New Zealand White rabbits according to USFDA (Fed. Reg. 37 (244), 27635, 1972) and draize test. A single 4 h, occluded application of the undiluted test substance to the intact skin of six rabbits produced distinct ischemia and very slight to slight oedema after 2 d. After 1 week, moderate incrustation and decreased hair growth were seen. No further observations were made. About similar observations were made using a 1 h exposure period. It was concluded by the author of the report that a 4 h exposure induced corrosive effects and a 1 h exposure did not. Under study conditions, the test substance was considered to be corrosive to the skin of rabbits (Beek, 1981).

Eye irritation

A study was conducted to determine the skin irritation potential of the test substance, TMAC C (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 test 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 test substance is considered to cause irreversible effects on the eye (Naas, 1988).

 

The biocide assessment report available from RMS Italy on TMAC C also concluded that: “according to the studies presented by both applicants, coco alkyltrimethylammonium chloride is corrosive for the skin and it is also severely irritant to the eyes” (ECHA biocides assessment report, 2016). Therefore, based on the available information and in line with the biocides assessment report, the test substance is considered to be corrosive to both skin and eyes.

Justification for classification or non-classification

Based on the results of the in vivo skin and eye irritation studies, the test substance warrants a '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.

With regard to respiratory tract irritation, although the test substance is very corrosive, its low vapour pressure prohibits the occurrence of respiratory irritation by vapour. Further, the classification of corrosive is already considered to implicitly cover the potential of RTI; therefore, an additional Cat.3 is considered to be superfluous (Guidance CLP Ch. 3.8.2.5).