Quaternary ammonium compounds, di-C14-18-alkyldimethyl, Me sulfates

Endpoint summary

Description of key information

- Skin irritation: not irritating (prior to implementation of GLP and OECD guidelines; RL2);

 

- Eye irritation: Category 1 (irreversible effects on the eye) (prior to implementation of GLP and OECD guidelines; RL2); moderate to severe eye irritation, which was not reversible after 14 d

Not irritating at 5% a.i.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

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:

comparable to guideline study with acceptable restrictions

Principles of method if other than guideline:

- Principle of test:
Six albino rats were used in this study. The hair was clipped from the back and flanks of each animal. The test material was applied to two areas on each of six animals, one abraded and one unabraded under a 1 x 1 inch 12 ply qauze 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 and 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. After 4 hours of exposure, the patches were removed and the resulting reactions evaluated on the basis of the score described ihn the bottom section.

- Short description of test conditions:
Animals were held individually in screen bottom cages and were supplied with food and water ad libitum. During the exposure time the animals were immobilised in stocks.

- Parameters analysed / observed: erythema, edema

GLP compliance:

no

Remarks:

study conducted prior to implementation of GLP

Species:

rabbit

Strain:

other: albino

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Housing: individually in screen bottom cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Type of coverage:

semiocclusive

Preparation of test site:

other: The hair was clipped and the substance was applied on intact and abraded skin

Vehicle:

unchanged (no vehicle)

Controls:

not specified

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:

6

Details on study design:

TEST SITE
- Type of wrap if used: 1 x 1 inch 12 ply gauze patch held in place by 1/2 inch adhesive tape.


OBSERVATION TIME POINTS
(indicate if minutes, hours or days) At 2 h, 4 h, 24 h, 48 h, 72 h

SCORING SYSTEM:
- Method of calculation:
The following score was used:

Erythema and Eschar formation: Score:
Slight erythema 1
Defined erythema 2
Moderate to severe erythema 3
Severe erythema to slight eschar formation 4

Edema formation: Score:
Slight edema (barly perceptible) 1
Defined edema (edges definite rising) 2
Moderate edema (area raised 1 mm) 3
Severe edema (raised more than 1 mm) 4

Irritation parameter:

erythema score

Remarks:

intact skin site

Basis:

animal: #1 - #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Remarks:

intact skin site

Basis:

animal: #1 - #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No edema or erythema were oberved at any time point, incl. 2 h and 4 h on intact and abraded skin sites.

Interpretation of results:

GHS criteria not met

Conclusions:

In this study, C14-18 alkyldimethyl ammonium methosulfate (89% a.i.) is not a dermal irritant.

Executive summary:

In a primary dermal irritation study conducted prior to implementation of GLP and OECD guidelines, 6 young adult albino rabbits were dermally exposed to 0.5 g of C14-18 alkyldimethyl ammonium methosulfate (89% a.i.) for 4 hours to intact and abraded skin.  Animals then were observed for 3 days.  Irritation was scored by the method of Draize after 2, 4, 24, 48 and 72 h.

All edema and erythema scores were 0 at all timepoints on intact and abraded skin.

In this study, C14-18 alkyldimethyl ammonium methosulfate (89% a.i.) is not a dermal irritant.

Reference 2

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:

comparable to guideline study with acceptable restrictions

Principles of method if other than guideline:

- Principle of test:
Six albino rats were used in this study. The hair was clipped from the back and flanks of each animal. The test material was applied to two areas on each of six animals, one abraded and one unabraded. After 24 hours of exposure, the patches were removed and the resulting reactions evaluated on the basis of the Draize scale.

- Short description of test conditions:
Animals were held individually in screen bottom cages and were supplied with food and water ad libitum. During the exposure time the animals were immobilised in stocks.

- Parameters analysed / observed: erythema, edema

GLP compliance:

no

Remarks:

study conducted prior to implementation of GLP

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: approx. 14 weeks
- Weight at study initiation: 2.5 - 3.5 kg
- Housing: individually in screen bottom cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 7 d

Type of coverage:

semiocclusive

Preparation of test site:

other: The hair was clipped and the substance was applied on intact and abraded skin

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

Duration of treatment / exposure:

24 h

Observation period:

72 h

Number of animals:

6

Details on study design:

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) At 24 h, 72 h

SCORING SYSTEM:
- Method of calculation:
The following score was used:

Erythema and Eschar formation: Score:
Slight erythema 1
Defined erythema 2
Moderate to severe erythema 3
Severe erythema to slight eschar formation 4

Edema formation: Score:
Slight edema (barly perceptible) 1
Defined edema (edges definite rising) 2
Moderate edema (area raised 1 mm) 3
Severe edema (raised more than 1 mm) 4

Irritation parameter:

erythema score

Remarks:

intact skin site

Basis:

animal: #1, 2, 3, 6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

no observation at 48 h

Irritation parameter:

erythema score

Remarks:

intact skin site

Basis:

animal: # 4, 5

Time point:

24/48/72 h

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: no observation at 48 h

Irritation parameter:

edema score

Remarks:

intact skin site

Basis:

animal: #1 - #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

no observation at 48 h

Irritant / corrosive response data:

Slight erythema (grade 1) was observed in 2/6 animals on the intact skin sites (and in 3/6 animals on abraded skin sites) at the 24 h observation, which was completely reversible within 72 h. Edema scored were 0 at both observation on intact and abraded skin.

Score at time point / Reversibility (intact skin site)	Erythema	Edema
	Max. score: 4	Max. score: 4
24 h	0/0/0/1/1/0	0/0/0/0/0/0
72 h	0/0/0/0/0/0	0/0/0/0/0/0
Average 24h, 72h	0/0/0/0.5/0.5/0	0/0/0/0/0/0
Reversibility	Completely reversible within 72 h	Not applicable

Score at time point / Reversibility (abraded skin site)	Erythema	Edema
	Max. score: 4	Max. score: 4
24 h	0/0/1/1/1/0	0/0/0/0/0/0
72 h	0/0/0/0/0/0	0/0/0/0/0/0
Average 24h, 72h	0/0/0.5/0.5/0.5/0	0/0/0/0/0/0
Reversibility	Completely reversible within 72 h	Not applicable

Interpretation of results:

GHS criteria not met

Conclusions:

In this study, C14-18 alkyldimethyl ammonium methosulfate (80% a.i.) is not a dermal irritant.

Executive summary:

In a primary dermal irritation study conducted prior to implementation of GLP and OECD guidelines, 6 young adult New Zealand White rabbits were dermally exposed to 0.5 g of C14-18 alkyldimethyl ammonium methosulfate (80% a.i.) for 24 hours to intact and abraded skin.  Animals then were observed for 3 days.  Irritation was scored by the method of Draize after 24 and 72 h.

Slight erythema (grade 1) was observed in 2/6 animals on the intact skin sites (3/6 animals on abraded skin sites) at the 24 h observation, which was completely reversible within 72 h. Edema scored were 0 at both observation on intact and abraded skin. 

In this study, C14-18 alkyldimethyl ammonium methosulfate (80% a.i.) is not a dermal irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Principles of method if other than guideline:

- Principle of test:
Six albino rabbits of the New Zealand strain were placed in a collar such that the animals could not rub their eyes. 0.1 g of the substance were instilled in one eye, the other untreated eye served as control. Damage to the cornea, iris and the bulbar and palpebral conjunctivae were scored at 24, 48 and 72 h after eye instillation. Any residue of the test material and accumulated discharge are flushed from the eye each time they are scored.
- Parameters analysed / observed:
Damage to the eye, i.e. opacity of the cornea and the area of opacity, reaction of the iris and redness, chemosis and discharge of the conjunctivae were scored.

GLP compliance:

no

Remarks:

study conducted prior to implementation of GLP

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

other: the contralateral, untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:

The substance was once instilled and the treated eye was flushed if any residual or accumulated test item was visible at each scoring time point.

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

6 animals

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): If residual or accumulated test substance was visible the treated eye was washed at each scoring time point
- Time after start of exposure: The first scoring time point was 24 h after eye instillation

SCORING SYSTEM: Draize scale

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #3, #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks:

duration of observation was 72 h

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not reversible

Remarks:

duration of observation was 72 h

Irritation parameter:

iris score

Basis:

animal: #1 - #6

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.67

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal: #2, #5

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

not reversible

Remarks:

duration of observation was 72 h

Irritation parameter:

conjunctivae score

Basis:

animal: #3, #6

Time point:

24/48/72 h

Score:

2.33

Max. score:

3

Reversibility:

not reversible

Remarks:

duration of observation was 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not reversible

Remarks:

duration of observation was 72 h

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

not reversible

Remarks:

duration of observation was 72 h

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

not reversible

Remarks:

duration of observation was 72 h

Irritation parameter:

chemosis score

Basis:

animal: #5, #6

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

not reversible

Remarks:

duration of observation was 72 h

Irritant / corrosive response data:

During the observation period, corneal opacity scores were 0 in 3/6 animals, 1 in 2/6 animals and 2 in 1/6 animals. Iris scores were 0 throughout the observation period. Conjunctival redness was scored 3 after 24 h in all animals, 2-3 after 48 h, and 0-2 after 72 h. Chemosis scores were 2-3 after 24 h, 2 after 48 h, and 0-2 after 72 h. As the animals were observed only for 72 h, and effects were still present at study termination, reversibility cannot finally be evaluated. Nevertheless, a tendency towards reversion was noted.

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility	Cornea	Iris	Conjunctivae	Chemosis
	Max. score: 4	Max. score: 2	Max. score: 3	Max. score: 4
24 h	0/2/0/0/1/1	0/0/0/0/0/0	3/3/3/3/3/3	2/3/2/2/3/3
48 h	0/2/0/0/1/1	0/0/0/0/0/0	2/3/2/2/3/2	2/2/2/2/2/2
72 h	0/2/0/0/0/1	0/0/0/0/0/0	0/2/2/1/2/2	0/2/0/1/2/2
Average 24h, 48h, 72h	0/2/0/0/0.67/1	0/0/0/0/0/0	1.67/2.67/2.33/2/2.67/2.33	1.33/2.33/1.33/1.67/2.67/2.67
Reversibility*)	n.c.	c.	n.c.	n.c.
Average time (unit) for reversion	72 h		72 h	72 h

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Interpretation of results:

study cannot be used for classification

Conclusions:

Based on scores for conjunctival redness and chemosis, C14-18 alkyldimethyl ammonium methosulfate (89% a.i.) has to be classified for eye irritation. However, discrimination between Category 1 and 2 is not possible based on this study.

Executive summary:

In a primary eye irritation study conducted prior to implementation of GLP and OECD guidelines 0.1 g of C14-18 alkyldimethyl ammonium methosulfate (89% a.i.) was instilled into the conjunctival sac of one eye of 6 adult New Zealand White rabbits. The substance was once instilled and the treated eye was flushed if any residual or accumulated test item was visible at each scoring time point (24, 48, 72 h). Animals were observed for 3 days.  Irritation was scored by the method of Draize.

During the observation period, corneal opacity scores were 0 in 3/6 animals, 1 in 2/6 animals and 2 in 1/6 animals. Iris scores were 0 throughout the observation period. Conjunctival redness was scored 3 after 24 h in all animals, 2-3 after 48 h, and 0-2 after 72 h. Chemosis scores were 2-3 after 24 h, 2 after 48 h, and 0-2 after 72 h. As the animals were observed only for 72 h, and effects were still present at study termination, reversibility cannot finally be evaluated. Nevertheless, a tendency towards reversion was noted.

Based on scores for conjunctival redness and chemosis, C14-18 alkyldimethyl ammonium methosulfate (89% a.i.) has to be classified for eye irritation. However, discrimination between Category 1 and 2 is not possible based on this study.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Principles of method if other than guideline:

Albino rabbits were housed in individual screen bottom cages and fed water and rabbit chow ad libitum. The hair was clipped from the back and flanks of
the animal. The test material was applied to two areas on each of six rabbits, 1 abraded area, and 1 intact area, in the amount of 0.5 ml per area in the case of liquids or 0.5 gm per area in the case of solids. The treated areas were covered with gauze patch and taped to maintain the test material in contact with the skin
and decrease the rate of evaporation. The animals were fitted with collars for a 24 hour period at which time the coverings were removed and the degree of erythema and edema were recorded according to the Draize scale. A second reading was taken at 72 hours. The average of the 24 and 72 hour readings were used to determine the primary irritation score for the sample.

GLP compliance:

no

Remarks:

study conducted prior to implementation of GLP

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated contralateral eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

The substance was once instilled and the treated eye was flushed if any residual or accumulated test item was visible at each scoring time point.

Observation period (in vivo):

72 h

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The substance was once instilled and the treated eye was flushed if any residual or accumulated test item was visible at each scoring time point.

SCORING SYSTEM: Draize scale

Irritation parameter:

cornea opacity score

Basis:

animal: #1-#6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal: #1-#6

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal: #1, #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal: #3-#6

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal: #1, #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal: #3-#6

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

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
24 h	0/0/0/0/0/0	0/0/0/0/0/0	1/1/2/2/2/2	1/1/1/1/1/1	1/1/1/1/1/1
48 h	0/0/0/0/0/0	0/0/0/0/0/0	1/1/1/1/1/1	0/0/1/1/1/1	0/0/0/0/0/0
72 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	0/0/0/0/0/0
Average 24h, 48h, 72h	0/0/0/0/0/0	0/0/0/0/0/0	0.67/0.67/1/1/1/1	0.33/0.33/0.67/0.67/0.67/0.67	0.33/0.33/0.33/0.33/0.33/0.33
Reversibility	---	---	Fully reversible within 72 h	Fully reversible within 72 h	Fully reversible within 48 h

Interpretation of results:

GHS criteria not met

Conclusions:

In this study, C14-18 alkyldimethyl ammonium methosulfate (5% a.i.) was not irritating to the eye.

Executive summary:

In a primary eye irritation study conducted prior to implementation of GLP and OECD guidelines 0.1 mL of C14-18 alkyldimethyl ammonium methosulfate (5% a.i.) was instilled into the conjunctival sac of one eye of 6 adult New Zealand White rabbits. The substance was once instilled and the treated eye was flushed if any residual or accumulated test item was visible at each scoring time point (24, 48, 72 h). Animals were observed for 3 days.  Irritation was scored by the method of Draize.

Corneal opacity and iris scored were 0 in all animals throughout the observation period. Grade 1 - 2 conjunctival redness was observed after 24 h, which was fully reversible within 72 h. Minimal chemosis (grade 1) was observed after 24 and 48 h, which was fully reversible within 72 h.

In this study, C14-18 alkyldimethyl ammonium methosulfate (5% a.i.) was not irritating to the eye. This study is used to set a specific concentration limit.

Reference 3

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Principles of method if other than guideline:

The hair was clipped from the back and flanks of the animal. The test material was applied to two areas on each rabbit, 1 abraded area, and 1 intact area, in the amount of 0.5 ml per area in the case of liquids or 0.5 gm per area in the case of solids. The treated areas were covered with a gauze patch and taped to maintain the test material in contact with the skin and decrease the rate of evaporation. The animals were immobilized for a 24 hour period at which time the coverings were removed and the degree of erythema and edema were recorded according to the Draize scale. A second reading was taken at 72 hours. The average of the 24 and 72 hour readings were used to determine the primary irritation index for the sample.

GLP compliance:

no

Remarks:

study conducted prior to implementation of GLP

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: approx. 14 weeks
- Weight at study initiation: 2.5 - 3.5 kg
- Housing: individually
- Diet (e.g. ad libitum): commercial laboratory feed ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 7 d



IN-LIFE DATES: From: To:

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated contralateral eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:

The substance was once instilled and the treated eye was flushed if any residual or accumulated test item was visible at each scoring time point.

Observation period (in vivo):

14 d

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The substance was once instilled and the treated eye was flushed if any residual or accumulated test item was visible at each scoring time point.

SCORING SYSTEM: Draize scale

Irritation parameter:

cornea opacity score

Basis:

animal: #1-#6

Remarks:

single scores are given in "Any other information on results"

Time point:

24/48/72 h

Score:

>= 1.67 - <= 4

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

iris score

Basis:

animal: #1-#6

Remarks:

single scores are given in "Any other information on results"

Time point:

24/48/72 h

Score:

>= 0 - <= 2

Max. score:

2

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

conjunctivae score

Basis:

animal: #1-#6

Remarks:

single scores are given in "Any other information on results"

Time point:

24/48/72 h

Score:

>= 2 - <= 2.67

Max. score:

3

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

animal: #1-#6

Remarks:

single scores are given in "Any other information on results"

Time point:

24/48/72 h

Score:

>= 2 - <= 2.67

Max. score:

4

Reversibility:

not fully reversible within: 14 d

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
24 h	3/2/1/3/4/2	0/1/1/2/2/0	2/2/2/2/2/2	2/3/2/3/3/3	3/2/3/2/2/2
48 h	2/2/2/2/4/2	0/0/0/1/2/0	2/2/2/2/3/2	2/2/2/2/2/2	3/3/3/3/3/2
72 h	2/2/2/2/4/2	0/0/0/0/2/0	2/2/2/2/3/3	2/2/2/2/2/3	2/2/2/2/2/2
7 d	4/3/3/4/4/4	2/2/2/2/2/1	3/2/2/3/2/2	2/2/2/2/2/2	2/2/2/2/2/2
14 d	4/3/3/4/4/1	0/0/0/2/2/0	2/2/2/2/2/2	2/2/3/1/2/1	2/2/3/1/2/1
Average 24h, 48h, 72h	2.33/2/1.67/2.33/4/2	0/0.33/0.33/1/2/0	2/2/2/2/2.67/2.33	2/2.33/2/2.33/2.33/2.67	2.67/2.33/2.67/2.33/2.33/2
Reversibility	Not reversible	Not reversible	Not reversible	Not reversible	Not reversible

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

In this study, C14-18 alkyldimethyl ammonium methosulfate (80% a.i.) caused irreversible effects on the eye.

Executive summary:

In a primary eye irritation study conducted prior to implementation of GLP and OECD guidelines 0.1 g of C14-18 alkyldimethyl ammonium methosulfate (80% a.i.) was instilled into the conjunctival sac of one eye of 6 adult New Zealand White rabbits. The substance was once instilled and the treated eye was flushed if any residual or accumulated test item was visible at each scoring time point (24, 48, 72 h, 7 d, 14 d). Animals were observed for 14 days.  Irritation was scored by the method of Draize.

Moderate to severe eye irritation, which was not reversible after 14 d, was noted in all animals throughout the observation period. In this study, C14-18 alkyldimethyl ammonium methosulfate (80% a.i.) caused irreversible effects on the eye.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Skin irritation

In a primary dermal irritation study conducted prior to implementation of GLP and OECD guidelines, 6 young adult New Zealand White rabbits were dermally exposed to 0.5 g of C14-18 alkyldimethyl ammonium methosulfate (80% a.i.) for 24 hours to intact and abraded skin.  Animals then were observed for 3 days.  Irritation was scored by the method of Draize after 24 and 72 h.

Slight erythema (grade 1) was observed in 2/6 animals on the intact skin sites (3/6 animals on abraded skin sites) at the 24 h observation, which was completely reversible within 72 h. Edema scored were 0 at both observation on intact and abraded skin. 

In this study, C14-18 alkyldimethyl ammonium methosulfate (80% a.i.) is not a dermal irritant.

 

In a primary dermal irritation study conducted prior to implementation of GLP and OECD guidelines, 6 young adult albino rabbits were dermally exposed to 0.5 g of C14-18 alkyldimethyl ammonium methosulfate (89% a.i.) for 4 hours to intact and abraded skin.  Animals then were observed for 3 days.  Irritation was scored by the method of Draize after 2, 4, 24, 48 and 72 h.

All edema and erythema scores were 0 at all timepoints on intact and abraded skin.

In this study, C14-18 alkyldimethyl ammonium methosulfate (89% a.i.) is not a dermal irritant.

 

Eye irritation

In a primary eye irritation study conducted prior to implementation of GLP and OECD guidelines 0.1 g of C14-18 alkyldimethyl ammonium methosulfate (89% a.i.) was instilled into the conjunctival sac of one eye of 6 adult New Zealand White rabbits. The substance was once instilled and the treated eye was flushed if any residual or accumulated test item was visible at each scoring time point (24, 48, 72 h). Animals were observed for 3 days.  Irritation was scored by the method of Draize.

During the observation period, corneal opacity scores were 0 in 3/6 animals, 1 in 2/6 animals and 2 in 1/6 animals. Iris scores were 0 throughout the observation period. Conjunctival redness was scored 3 after 24 h in all animals, 2-3 after 48 h, and 0-2 after 72 h. Chemosis scores were 2-3 after 24 h, 2 after 48 h, and 0-2 after 72 h. As the animals were observed only for 72 h, and effects were still present at study termination, reversibility cannot finally be evaluated. Nevertheless, a tendency towards reversion was noted.

Based on scores for conjunctival redness and chemosis, C14-18 alkyldimethyl ammonium methosulfate (89% a.i.) has to be classified for eye irritation. However, discrimination between Category 1 and 2 is not possible based on this study.

 

In a primary eye irritation study conducted prior to implementation of GLP and OECD guidelines 0.1 g of C14-18 alkyldimethyl ammonium methosulfate (80% a.i.) was instilled into the conjunctival sac of one eye of 6 adult New Zealand White rabbits. The substance was once instilled and the treated eye was flushed if any residual or accumulated test item was visible at each scoring time point (24, 48, 72 h, 7 d, 14 d). Animals were observed for 14 days.  Irritation was scored by the method of Draize.

Moderate to severe eye irritation, which was not reversible after 14 d, was noted in all animals throughout the observation period. In this study, C14-18 alkyldimethyl ammonium methosulfate (80% a.i.) caused irreversible effects on the eye.

 

In a primary eye irritation study conducted prior to implementation of GLP and OECD guidelines 0.1 mL of C14-18 alkyldimethyl ammonium methosulfate (5% a.i.) was instilled into the conjunctival sac of one eye of 6 adult New Zealand White rabbits. The substance was once instilled and the treated eye was flushed if any residual or accumulated test item was visible at each scoring time point (24, 48, 72 h). Animals were observed for 3 days.  Irritation was scored by the method of Draize.

Corneal opacity and iris scored were 0 in all animals throughout the observation period. Grade 1 - 2 conjunctival redness was observed after 24 h, which was fully reversible within 72 h. Minimal chemosis (grade 1) was observed after 24 and 48 h, which was fully reversible within 72 h.

In this study, C14-18 alkyldimethyl ammonium methosulfate (5% a.i.) was not irritating to the eye. This study is used to set a specific concentration limit.

 

 

Respiratory irritation

No data on the respiratory irritation of C14-18 alkyldimethyl ammonium methosulfate are available.

  

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, C14-18 alkyldimethyl ammonium methosulfate is not classified for skin irritation, but has to be classified as Category 1 (Serious eye damage) according to CLP, EU GHS (Regulation (EC) No 1272/2008) and is assigned the hazard statement H318 and the signal word “Danger”.