Registration Dossier

Administrative data

Description of key information

- Skin irritation: Category 1 (corrosive)

WoE:

- 4 h under semi-occlusive conditions, observation for 72 h: severe erythema and severe edema (scores 3-4), blanching; FIFRA (11/82) / TSCA (8/82), GLP, RL2

- 4 h under occlusive conditions (75% in water/isopropanol), skin reactions are described as corrosive after 24 h; study conducted before implementation of GLP and OECD guidelines

(no distiction between Cat 1 B and Cat 1 C possible) 

 

- Eye irritation: Category 1 (irreversible effects on the eye); corneal opacity scores 2-3, iris scores 0-2, corneal redness scores 2-3, chemosis scores 3-4; not reversible within the observation period of 7 days; blanching, corneal epithelial damage, fluorescein retention; FIFRA (11/82) / TSCA (8/82), GLP, RL2

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:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
In a primary dermal irritation study 6 female albino rabbits were dermally exposed to C12-18 alkyldimethyl ammonium chloride (75% in water/isopropanol) for 4 h under occlusive conditions on intact and abraded skin. Animals then were observed for 24 h.
GLP compliance:
no
Remarks:
test conducted before implementation of GLP
Species:
rabbit
Strain:
other: albine strain, no further specification
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: no data
- Weight at study initiation: no data
- Housing: individually in screen bottom cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data
Type of coverage:
occlusive
Preparation of test site:
other: one side clipped, one side clipped + abraded
Vehicle:
unchanged (no vehicle)
Observation period:
24 h
Number of animals:
6
Details on study design:
TEST SITE
The test material was applied under a 1 x 1 inch 12 ply gauze patch held in place by 1/2 inch adhesive tape applied as an "X" over the patch. The trunk of the animals was then loosely wrapped in an impervious wrap for an exposure period of 4 hours. The wrap was applied loosely enough for the palm of the hand to be inserted between it and the animals back.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

OBSERVATION TIME POINTS
2, 4, 24 hours

SCORING SYSTEM:
- Draize scale
Irritation parameter:
erythema score
Basis:
animal: #1-#6
Time point:
24 h
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Remarks:
effects were classified as corrosive; no further observation after 24 h
Irritation parameter:
edema score
Basis:
animal: #1-#6
Time point:
24 h
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Remarks:
effects were classified as corrosive; no further observation after 24 h
Irritation parameter:
erythema score
Remarks:
abraded and intact sites
Basis:
animal: #1-6
Time point:
other: 2 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Remarks:
abraded and intact sites
Basis:
animal: #1-6
Time point:
other: 2 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Remarks:
abraded and intact sites
Basis:
animal: #1-6
Time point:
other: 4 h
Score:
2
Max. score:
4
Irritation parameter:
edema score
Remarks:
abraded and intact sites
Basis:
animal: #1-6
Time point:
other: 4 h
Score:
2
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal: #1-6
Time point:
24/48/72 h
Reversibility:
not reversible
Remarks on result:
not measured/tested
Remarks:
no observation after 24 h; thus, no mean can be calculated
Irritation parameter:
edema score
Basis:
animal: #1-6
Time point:
24/48/72 h
Reversibility:
not reversible
Remarks on result:
not measured/tested
Remarks:
no observation after 24 h; thus, no mean can be calculated
Irritant / corrosive response data:
Irreversible damage to the skin classifies the material as corrosive (effects are not described in detail in the study report).

Score at time point / Reversibility

Erythema – intact skin site

Edema – intact skin site

Erythema – abraded skin site

Edema – abraded skin site

Max. score: 4

Max. score: 4

Max. score: 4

Max. score: 4

2 h

0/0/0/0/0/0

0/0/0/0/0/0

0/0/0/0/0/0

0/0/0/0/0/0

4 h

2/2/2/2/2/2 

2/2/2/2/2/2 

2/2/2/2/2/2 

2/2/2/2/2/2 

24 h

c/c/c/c/c/c 

c/c/c/c/c/c 

c/c/c/c/c/c 

c/c/c/c/c/c 

 

C = Irreversible damage to the skin classifies the material as corrosive.

Interpretation of results:
Category 1 (corrosive) based on GHS criteria
Conclusions:
Under the conditions of the test, Di-C12-18 alkyldimethyl ammonium chloride (75% in water/isopropanol) is corrosive to the skin.
Executive summary:

In a primary dermal irritation study conducted before implementation of GLP and OECD guidelines 6 female albino rabbits were dermally exposed to Di-C12-18 alkyldimethyl ammonium chloride (75% in water/isopropanol) for 4 h under occlusive conditions on intact and abraded skin. Animals then were observed for 24 h. Irritation was scored by the Draize scale.

After 2 h, no skin reactions were observed. After 4 hours, erythema and edema scores were 2 in all animals on intact an abraded skin sites. After 24 h, skin reactions are described as corrosive (irreversible damage) without further specification in the study report.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
according to
Guideline:
other: Environmental Protection Agency FIFRA (11/82) and TSCA (8/82) guidelines
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: adults
- Weight at study initiation: 3867 to 4536 g
- Housing: Individually in suspended wire-mesh cages
- Diet (e.g. ad libitum): Purina Certified Rabbit Chow #5322, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 7 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 20.5
- Humidity (%): 32 - 52
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
semiocclusive
Preparation of test site:
other: one site intact, one site abraded
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g


Duration of treatment / exposure:
4 h
Observation period:
72 h
Number of animals:
3 females
Details on study design:
TEST SITE
- Area of exposure: 2.5*2.5 cm²
- Type of wrap if used: Gauze patches were overwrapped with a gauze binder that was 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
- Washing (if done): sites were wiped with wet disposable paper towels
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
(indicate if minutes, hours or days)
ca. 4-5, 24, 48, 72 h

SCORING SYSTEM:
- Dermal irritation was graded in accordance with the method of Draize
Irritation parameter:
erythema score
Remarks:
intact skin site
Basis:
animal: #1, 2, 3
Time point:
24/48/72 h
Score:
3.67
Max. score:
4
Reversibility:
not reversible
Remarks:
72 h
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
intact skin site
Basis:
animal: #1, 2
Time point:
24/48/72 h
Score:
3.67
Max. score:
4
Reversibility:
not reversible
Remarks:
72 h
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
intact skin site
Basis:
animal #3
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks:
72 h
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
The test material induced severe erythema and severe edema on all sites, although these levels of irritation generally were not observed until 48 hours. In addition, blanching was noted on both sites for one rabbit.
Other effects:
There were no deaths or remarkable body weight changes during the study period.

 

Score at time point / Reversibility

Erythema – intact skin site

Edema – intact skin site

Erythema – abraded skin site

Edema – abraded skin site

Max. score: 4

Max. score: 4

Max. score: 4

Max. score: 4

4 - 5 h

2/3/3

1/1/1

3/3/3

2/2/1

24 h

3/3b/3

3/3/4

3/3b/3

4/3/4

48 h

4/4/4

4/4/4

4/4/4

4/4/4

72 h

4/4b/4

4/4/4

4/4b/4

4/4/4

Mean 24/48/72 h

3.67/3.67/3.67

3.67/3.67/4

3.67/3.67/3.67

4/3.67/4

b = blanching

Interpretation of results:
Category 1 (corrosive) based on GHS criteria
Conclusions:
In this study, Di-C12-18 alkyldimethyl ammonium chloride (100%) was severely irritating to rabbit skin.
Executive summary:

In a primary dermal irritation study conducted according to Environmental Protection Agency FIFRA (11/82) and TSCA (8/82) guidelines 3 female albino rabbits were dermally exposed to Di-C12-18 alkyldimethyl ammonium chloride (100%) for 4 h under semi-occlusive conditions on intact and abraded skin. Animals then were observed for 72 h. Irritation was scored by the Draize scale.

There were no deaths or remarkable body weight changes during the study period. The test material induced severe erythema and severe edema on all sites (scores 3-4), although these levels of irritation generally were not observed until 48 hours. In addition, blanching was noted on both sites for one rabbit. The substance is classified as Category 1 (corrosive) based on GHS criteria.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
according to
Guideline:
other: Environmental Protection Agency FIFRA (11/82) and TSCA (8/82) guidelines
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: adults
- Weight at study initiation: 3883 to 5461 g
- Housing: Individually in suspended wire-mesh cages
- Diet (e.g. ad libitum): Purina Certified Rabbit Chow #5322, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 7 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 20.5
- Humidity (%): 32 - 70
- Photoperiod (hrs dark / hrs light): 12/12
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
Duration of treatment / exposure:
In one group the eyes of three rabbits were washed with 120 milliliters of lukewarm tap water commencing approximately 30 seconds after dosing. In the other 3 animals, eyes were not rinsed.
Observation period (in vivo):
7 d
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): In one group the eyes of three rabbits were washed with 120 milliliters of lukewarm tap water commencing approximately 30 seconds after dosing. In the other 3 animals, eyes were not rinsed.
Left eyes were manipulated in an identical manner, including washing, if applicable, to simulate the dosing of the right eyes.

SCORING SYSTEM: Draize scale

TOOL USED TO ASSESS SCORE: sodium fluorescein and ultraviolet light (72 h and 7 d)
Irritation parameter:
cornea opacity score
Remarks:
unwashed eyes
Basis:
animal: 1-3
Time point:
24/48/72 h
Score:
>= 2.33 - <= 3.33
Max. score:
4
Reversibility:
not fully reversible within: 7 d
Remarks:
only 7 d observation; final evaluation of reversibility not possible
Irritation parameter:
iris score
Remarks:
unwashed eyes
Basis:
animal: 1 - 3
Time point:
24/48/72 h
Score:
>= 1 - <= 2
Max. score:
2
Reversibility:
not fully reversible within: 7 d
Remarks:
only 7 d observation; final evaluation of reversibility not possible
Irritation parameter:
conjunctivae score
Remarks:
unwashed eyes
Basis:
animal: 1 - 3
Time point:
24/48/72 h
Score:
>= 1 - <= 2.67
Max. score:
3
Reversibility:
not fully reversible within: 7 d
Remarks:
only 7 d observation; final evaluation of reversibility not possible
Irritation parameter:
chemosis score
Remarks:
unwashed eyes
Basis:
animal: 1 - 3
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 7 d
Remarks:
only 7 d observation; final evaluation of reversibility not possible
Irritant / corrosive response data:
The untreated left eyes of all rabbits were free of evidence of ocular irritation and other findings for the duration of the study.
All three ocular structures were affected by instillation of the test item. Findings included hemorrhages, blanching, corneal epithelia damage (peeling).
Irritation was less in the washed group. Also, some limited evidence of recovery was present in the washed group. Based on the data obtained, the test material is considered to cause irreversible effects to the eye.
Other effects:
There were no deaths during the study period. None of the rabbits vocalized upon instillation of the test material.
Slight body weight losses were observed for three rabbits. These losses were possibly stress-related due to the severe irritation observed. No other remarkable body weight changes were noted.

Eyes not rinsed after instillation of test item

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Discharge

 

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

Max. score: 3

1 h

3/2/4

1/1/1

2/2/2

3/3/3

3/3/3

24 h

2/2/4

1/1/2

1/2/1

4/4/4

3/3/3

48 h

2/2/3

1/1/2

1/3/1

4/4/4

3/3/3

72 h

3/3/3

2/1/2

1/3/1

4/4/4

3/3/3

4 d

3/3/3

2/2/2

1/3/2

4/4/4

3/2/2

7 d

3/4/4

2/2/2

2/3/2

4/3/4

1/1/3

Average 24h, 48h, 72h

2.33/2.33/3.33

1.33/1/2

1/2.67/1

4/4/4

3/3/3

Reversibility

No

No

No

No

No

 

Eyes rinsed 30 s after instillation of test item

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Discharge

 

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

Max. score: 3

1 h

2/2/1

1/1/2

2/2/1

3/2/1

2/2/3

24 h

2/2/2

1/2/1

1/2/2

4/4/4

3/3/3

48 h

3/3/2

1/1/1

3/3/3

4/4/4

3/3/3

72 h

3/3/2

1/2/0

3/3/2

4/4/3

2/3/1

4 d

3/3/2

2/2/0

3/3/3

4/4/4

2/3/3

7 d

3/3/2

1/2/0

3/3/3

3/4/4

1/3/3

Average 24h, 48h, 72h

2.67/2.67/2

1/1.67/0.67

2.33/2.67/2.33

4/4/3.67

2.67/3/2.33

Reversibility

No

No

No

No

No

 

Animal

 

Timepoint

 

1

unwashed

1 h

b,d,e(100%)

 

 

24 h

a, d

 

 

48 h

a, d, e(100%)

 

 

72 h

a, d, e(100%), r(100%)

 

 

4 d

a, d, e(100%)

 

 

7 d

a, e(100%), r(100%)

2

unwashed

1 h

a, e (90%)

 

 

24 h

a, d

 

 

48 h

a, c, e (90%)

 

 

72 h

a, c, e (90%), r(90%)

 

 

4 d

a, c, e (90%)

 

 

7 d

b, c, e(50%), k, r(50%)

3

unwashed

1 h

a, d, e(100%)

 

 

24 h

a, d

 

 

48 h

a, d, e(100%)

 

 

72 h

a, d, e(100%), r(100%)

 

 

4 d

a, c, d, e(100%)

 

 

7 d

a, c, d, e(100%), r(100%)

4

washed

1 h

b, c, e(50%)

 

 

24 h

a, d

 

 

48 h

a, e(100%)

 

 

72 h

a, c, e(85%), r(85%)

 

 

4 d

a, c, e(85%)

 

 

7 d

b, c, e(30%), k, r(30%)

5

washed

1 h

b, e(80%)

 

 

24 h

a, d

 

 

48 h

a, c, e(100%)

 

 

72 h

a, c, e(100%), r(100%), s

 

 

4 d

a, c, e(100%), s

 

 

7 d

b, c, e(100%), r(100%), s

6

washed

1 h

b, e (20%)

 

 

24 h

a, d

 

 

48 h

a, c, e(100%)

 

 

72 h

b, c, e(100%), r(100%)

 

 

4 d

b, c, e(100%)

 

 

7 d

b, c, e(35%), r(35%)

 

a = Purulent Discharge

b = Clear discharge

c = Petite hemorrhage

d = Blanching

e = Corneal epithelial damage, peeling (% of area)

k = Corneal neovascularization

r = Sodium fluorescein stain retention (% of area)

s = Blood present in anterior chamber

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
In this study, Di-C12-18 alkyldimethyl ammonium chloride (100% a.i.) caused irreversible effects to the eyes.
Executive summary:

In a primary eye irritation study according to Environmental Protection Agency FIFRA (11/82) and TSCA (8/82) guidelines 0.1 mL of Di-C12-18 alkyldimethyl ammonium chloride (100% a.i.) was instilled into the conjunctival sac of the right eye of 6 female New Zealand White rabbits. In one group of three, the eyes were washed with 120 milliliters of lukewarm tap water commencing approximately 30 seconds after dosing; in the remaining three animals the eyes were not washed. The left eyes were manipulated in an identical manner, including washing, if applicable, to simulate the dosing of the right eyes. Animals then were observed for 7 days. Irritation was scored by the method of Draize.

All three ocular structures were affected by instillation of the test item. Irritation was less in the washed group. Also, some limited evidence of recovery was present in the washed group. In the group without rinsing after instillation, corneal opacity scores ranged from 2 to 3. Iris scores up to 2 were observed. Corneal redness scores of 2-3 and chemosis scores of 3 – 4 were observed. The effects were not reversible within the observation period of 7 days. Additionally, effects like blanching, corneal epithelial damage, and fluorescein retention were observed.

Based on the data obtained, the test material is considered to cause irreversible effects to the eye.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

For the assessment of skin irritating properties of Di-C12-18 alkyldimethyl ammonium chloride, two in vivo studies are available.

 

In a primary dermal irritation study conducted according to Environmental Protection Agency FIFRA (11/82) and TSCA (8/82) guidelines 3 female albino rabbits were dermally exposed to Di-C12-18 alkyldimethyl ammonium chloride (100%) for 4 h under semi-occlusive conditions on intact and abraded skin. Animals then were observed for 72 h. Irritation was scored by the Draize scale.

There were no deaths or remarkable body weight changes during the study period. The test material induced severe erythema and severe edema on all sites (scores 3-4), although these levels of irritation generally were not observed until 48 hours. In addition, blanching was noted on both sites for one rabbit. The substance is classified as Category 1 (corrosive) based on GHS criteria.

 

In a primary dermal irritation study conducted before implementation of GLP and OECD guidelines 6 female albino rabbits were dermally exposed to Di-C12-18 alkyldimethyl ammonium chloride (75% in water/isopropanol) for 4 h under occlusive conditions on intact and abraded skin. Animals then were observed for 24 h. Irritation was scored by the Draize scale.

After 2 h, no skin reactions were observed. After 4 hours, erythema and edema scores were 2 in all animals on intact an abraded skin sites. After 24 h, skin reactions are described as corrosive (irreversible damage) without further specification in the study report.

 

Eye irritation

For the assessment of eye irritating properties of Di-C12-18 alkyldimethyl ammonium chloride, an in vivo study is available.

 

In a primary eye irritation study according to Environmental Protection Agency FIFRA (11/82) and TSCA (8/82) guidelines 0.1 mL of Di-C12-18 alkyldimethyl ammonium chloride (100% a.i.) was instilled into the conjunctival sac of the right eye of 6 female New Zealand White rabbits. In one group of three, the eyes were washed with 120 milliliters of lukewarm tap water commencing approximately 30 seconds after dosing; in the remaining three animals the eyes were not washed. The left eyes were manipulated in an identical manner, including washing, if applicable, to simulate the dosing of the right eyes. Animals then were observed for 7 days. Irritation was scored by the method of Draize.

All three ocular structures were affected by instillation of the test item. Irritation was less in the washed group. Also, some limited evidence of recovery was present in the washed group. In the group without rinsing after instillation, corneal opacity scores ranged from 2 to 3. Iris scores up to 2 were observed. Corneal redness scores of 2-3 and chemosis scores of 3 – 4 were observed. The effects were not reversible within the observation period of 7 days. Additionally, effects like blanching, corneal epithelial damage, and fluorescein retention were observed.

Based on the data obtained, the test material is considered to cause irreversible effects to the eye.

 

Respiratory irritation

No data on the respiratory irritation of Di-C12-18 alkyldimethyl ammonium chloride are available. However, classification as “corrosive” implies, that the substance is also corrosive to the respiratory tract.

  

There are no data gaps for the endpoint irritation/corrosion. No human information is available for this endpoint. However, there is no reason to believe that these results would not be applicable to humans.

Justification for classification or non-classification

Based on reliable, adequate and relevant data, Di-C12-18 alkyldimethyl ammonium chloride has to be classified as Category 1 (Causes severe skin burns and eye damage) according to CLP, EU GHS (Regulation (EC) No 1272/2008) and is assigned the hazard statement H314 and the signal word “Danger”.