N-(4-(methoxybenzyl))-N,N-dimethylanilinium hexafluoroantimonate

Endpoint summary

Description of key information

The irritation and corrosion studies returned negative results and therefore the test substance is not classified.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Dec. 15, 2003 to Jan. 28, 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

July 17, 1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source (i.e. manufacturer or supplier) and lot/batch number of test material: 3M Corporate Toxicology

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature and humidity

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing (e.g. warming, grinding): The test article was individually weighed and moistened with 0.3 ml of distilled water to form a paste.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Millbrook Breeding Labs, Amherst, MA
- Age at study initiation: 10-11 weeks
- Weight at study initiation: 2.2 - 2.7 kg
- Housing: The animals were housed 1/cage in suspended wire cages. Bedding was placed beneath the cages and changed at least three times/week. The animal room, reserved exclusively for rabbits on acute tests, was temperature controlled, had a 12 hour light/dark cycle, and was kept clean and vermin free.
- Diet (e.g. ad libitum): Fresh PMI Rabbit Chow (Diet #5321) was provided daily
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):12 hour light/dark cycle

IN-LIFE DATES: From: Dec. 16, 2003 To: Ja. 2, 2004

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Remarks:

The day prior to application of the test article, the dorsal area of the trunk of each animal was clipped free of hair. The prepared site, was approximately 10 x 10 cm and remained intact.

Vehicle:

water

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
VEHICLE
- Amount(s) applied (volume or weight with unit): The test article was individually weighed and moistened with 0.3 ml of distilled water to form a paste.

Duration of treatment / exposure:

3 min, 1 h, 4 h (Animal 1)
4 h (Animal 2 & 3))
The test article (0.5 g) was applied dermally to three intact sites for an exposure period of three minutes on site #1, one hour on site #2 and four hours on site #3.

Observation period:

Dermal reactions were scored at 60 minutes after each patch removal on all three sites. Site #3 was scored again at 24, 48 and 72 hours.

Number of animals:

3 (Animal 1 and Animal 3: males, Animal 2: female)

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- % coverage:
- Type of wrap if used: plastic (semi-occlusive)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): distilled water
- Time after start of exposure: Animal 1 (male) - 3 min (site #1), 1h (site #2), 4h (site #3). Animal 2 (female) and Animal 3 (male) - 4h (site #3)

OBSERVATION TIME POINTS
(indicate if minutes, hours or days)
The test sites of all animals were scored for dermal irritation at 60 minutes after removal of wrappings. Site #3 was scored at 24, 48 and 72 hours.

SCORING SYSTEM:
- Method of calculation: Erythema and edema were scored according to the numerical Draize technique. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction.

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

Male, Site #1 - 3min exposure

Time point:

other: 1 h

Score:

0

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

Male, Site #2 - 1h exposure

Time point:

other: 1 h

Score:

0

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

Male, Site #3 - 4h exposure

Time point:

other: 1 h

Score:

0

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

Female, Site #3 - 4h exposure

Time point:

other: 1 h

Score:

0

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

Male, Site #3 - 4h exposure

Time point:

other: 1 h

Score:

0

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

Male, Site #3 - 4h exposure

Time point:

24/48/72 h

Score:

0

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

Female, Site #3 - 4h exposure

Time point:

24/48/72 h

Score:

0

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

Male, Site #3 - 4h exposure

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

Male, Site #1 - 3min exposure

Time point:

other: 1 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

Male, Site #2 - 1h exposure

Time point:

other: 1 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

Male, Site #3 - 1h exposure

Time point:

other: 1 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

Male, Site #3 - 4h exposure

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

Female, Site #3 - 4h exposure

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

Male, Site #3 - 4h exposure

Time point:

24/48/72 h

Score:

0

Irritant / corrosive response data:

Dermal Observations (Table 1)
Initial animal- There was no erythema or edema noted-at any of the observation time periods.
Additional animals - There was no erythema or edema noted at any observation time period.

Other effects:

Systemic Observations (Table 1)
There were no abnormal physical signs noted during the observation period.
All body weight changes were normal.

Table 1: Dermal Observations, Body Weight and Systemic Observations
	Animal No	Animal 1	Animal 2	Animal 3
	Sex	M	F	M
	Pretest Body Weight - Kg	2.2	2.6	2.7
	Terminal Body Weight - Kg	2.5	2.6	2.7
Exposure time	Time after patch removal	Erythema & Escar Formation			Mean scores
Site #1 - 3 min	1h	0	N/A	N/A
Site #2 - 1h	1h	0	N/A	N/A
Site #3 - 4h	1h	0	0	0	0
Site #3 - 4h	24h	0	0	0	0
Site #3 - 4h	48h	0	0	0	0
Site #3 - 4h	72h	0	0	0	0
Exposure time	Time after patch removal	Edema			Mean scores
Site #1 - 3 min	1h	0	N/A	N/A
Site #2 - 1h	1h	0	N/A	N/A
Site #3 - 4h	1h	0	0	0	0
Site #3 - 4h	24h	0	0	0	0
Site #3 - 4h	48h	0	0	0	0
Site #3 - 4h	72h	0	0	0	0
		Sum of Mean Scores =			0
		Modified Primary Irritation Index(PII)= Sum of Mean Scores/2=			0
		Systemic observations
	1h	A	A	A
	24h	A	A	A
	48h	A	A	A
	72h	A	A	A
		A=Normal
		N/A = not applicable

Interpretation of results:

GHS criteria not met

Conclusions:

N-(4-(methoxybenzyl))-N,N-dimethylanilinium hexafluoroantimonate is not a dermal irritant.

Executive summary:

There was no erythema or edema noted at any of the observation time periods in any animal.
There were no abnormal physical signs noted during the observation period. All body weight changes were normal.

The Modified Primary Irritation Index for the test substance is 0 and thus it is not a dermal irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From Jan 5, 2004 to Feb. 26, 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

February 24, 1987

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source (i.e. manufacturer or supplier) and lot/batch number of test material: 3M Corporate Toxicology

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature and humidity

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Millbrook Breeding Labs, Amherst, MA
- Age at study initiation: 13 weeks
- Weight at study initiation: 2.6 - 3.0 kg
- Housing: The animals were housed 1/cage in suspended cages. Bedding was placed beneath the cages and changed at least three times/week. The animal room, reserved exclusively for rabbits on acute tests, was temperature controlled, had a 12 hour light/dark cycle and was kept clean and vermin free
- Diet (e.g. ad libitum): Fresh PMI Rabbit Chow (Diet #5321) daily
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Rabbits equilibrated for at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

IN-LIFE DATES: From: Jan. 5, 2004 To: Jan. 19, 2004

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 76 mg

Duration of treatment / exposure:

After instillation, the lids were held together for approximately one second to insure adequate distribution of the test article.

Observation period (in vivo):

1, 24, 48 and 72 hours postdose and on day 7

Number of animals or in vitro replicates:

Three, 1 female, 2 males.

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not indicated

SCORING SYSTEM:
TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein

Using a Mini-Maglite® flashlight equipped with a high intensity bulb, the treated eye of each rabbit was examined for irritation of the cornea, iris and conjunctiva at 1, 24, 48 and 72 hours postdose and on day 7. Sodium fluorescein dye procedures were used at the 24, 48 and 72 hour observation interval, and again on day 7 in the initial animal, and at the 24 hour observation period in the two additional animals. The eye was examined with the aid of an ultraviolet light source. Ocular reactions were graded according to the numerical Draize technique.

Body weights were recorded pretest.
The general health of the animals was monitored at each observation time. All animals were humanely sacrificed using CO2 following study termination.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

Female, Mean score (following grading at 24, 48, and 72 h)

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

Remarks:

Male, Mean score (following grading at 24, 48, and 72 h)

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 #3

Remarks:

Male, Mean score (following grading at 24, 48, and 72 h)

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

Remarks:

Female, Mean 24/48/72h

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

Male, Mean score (following grading at 24, 48, and 72 h)

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

Male, Mean score (following grading at 24, 48, and 72 h)

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #1

Remarks:

Female, Mean score (following grading at 24, 48, and 72 h)

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 d

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #2

Remarks:

Male, Mean score (following grading at 24, 48, and 72 h)

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 d

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #3

Remarks:

Male, Mean score (following grading at 24, 48, and 72 h)

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 d

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

Female, Mean score (following grading at 24, 48, and 72 h)

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 d

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

Male, Mean score (following grading at 24, 48, and 72 h)

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 7 d

Remarks on result:

no indication of irritation

Irritation parameter:

other: Sodium Fluorescein

Basis:

animal #1

Remarks:

Female

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

positive indication of irritation

Irritation parameter:

other: Sodium Fluorescein

Basis:

animal #1

Remarks:

Female

Time point:

7 d

Score:

0

Max. score:

4

Irritation parameter:

other: Sodium Fluorescein

Basis:

animal #2

Remarks:

Male

Time point:

24 h

Score:

0

Max. score:

4

Irritation parameter:

other: Sodium Fluorescein

Basis:

animal #3

Remarks:

Male

Time point:

24 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Ocular findings (Table 1)
There was no corneal opacity noted at any observation period although fluorescein stain retention was noted in one eye. Iritis was noted in one eye at 24 hours and cleared by 48 hours. Conjunctival irritation, noted in 3/3 eyes, cleared by day 7.

Mean scores, following grading at 24, 48, and 72 h:
Corneal opacity: No animal has corneal opacity. The mean score (following grading at 24, 48, and 72 h) = (0+0+0)/3 = 0.  
Iritis: 1 animal has Iritis at 24h and cleared by 48h. The mean score (following grading at 24, 48, and 72 h) = (1+0+0)/3=0.33. The score is <1.
Conjunctival redness: 3 animals have conjunctival redness. The mean score score (following grading at 24, 48, and 72 h) for animal 1 is (1+1+1)/3 = 1. Similar for animals 2 and 3. All scores are < 2. 
Conjunctival chemosis: 3 animals have conjunctival chemosis. The mean score (following grading at 24, 48, and 72 h) for animal 1 is (2+2+2)/3 = 2. The mean score for animal 2 is (2+1+1)/3 = 1.67. The mean score for animal 3 is (2+1+1)/3 = 1.67. 1/3 score is 2. 2/3 scores are <2. 

Other effects:

Systemic Observations (Table 1)
There were no abnormal physical signs noted during the observation period.

 

Table 1. Ocular Findings and Systemic Observations

An.#/Sex	Item	Tissue	Reading	Hour 1	Hour 24	Hour 48	Hour 72	Day 7
1/F	A	Cornea	Opacity	0	0	0 h	0 h	0
	B		Area	0	0	0	0	0
		1. Total=(AxB)x5		0	0	0	0	0
	C	Iris		0	1	0	0	0
		2. Total = Cx5		0	5	0	0	0
	D	Conjuctiva	Redness	1	1	1	1	0
	E		Chemosis	2	2	2	2	0
	F		Discharge	2	2	2	1	0
		3. Total = (D+E+F)x2		10	10	10	8	0
		Total=1 +2+3		10	15	10	8	0
		Systemic Observations		A	A	A	A	A
		Sodium Fluorescein			1	1	1	0
		Pretest Body Weight - 2.9 kg
An.#/Sex	Item	Tissue	Reading	Hour 1	Hour 24	Hour 48	Hour 72	Day 7
2/M	A	Cornea	Opacity	0	0	0	0	0
	B		Area	0	0	0	0	0
		1. Total=(AxB)x5		0	0	0	0	0
	C	Iris		0	0	0	0	0
		2. Total = Cx5		0	0	0	0	0
	D	Conjuctiva	Redness	1	1	1	1	0
	E		Chemosis	2	2	2	1	0
	F		Discharge	2	1	0	0	0
		3. Total = (D+E+F)x2		10	8	6	4	0
		Total=1 +2+3		10	8	6	4	0
		Systemic Observations		A	A	A	A	A
		Sodium Fluorescein			0
		Pretest Body Weight - 2.6 kg
An.#/Sex	Item	Tissue	Reading	Hour 1	Hour 24	Hour 48	Hour 72	Day 7
3/M	A	Cornea	Opacity	0	0	0	0	0
	B		Area	0	0	0	0	0
		1. Total=(AxB)x5		0	0	0	0	0
	C	Iris		0	0	0	0	0
		2. Total = Cx5		0	0	0	0	0
	D	Conjuctiva	Redness	1	1	1	1	0
	E		Chemosis	1	2	2	1	0
	F		Discharge	2	2	0	0	0
		3. Total = (D+E+F)x2		8	10	6	4	0
		Total=1 +2+3		8	10	6	4	0
		Systemic Observations		A	A	A	A	A
		Sodium Fluorescein			0
		Pretest Body Weight - 3.0 kg
		A = Normal h = lack ofnormal luster

 

SCALE FOR SCORING OCULAR LESIONS (Draize, J. H. et al. J. Pharm. Exp. Ther. 82:377-390, 1944.)	Score
1) CORNEA:
(A) Opacity: Degree of density (area most dense taken for reading):
No ulceration or opacity	0
Scattered or diffuse areas of opacity (other than slight dulling of normalluster),details of iris clearly visible	1	*
Easily discernible translucent area, details of iris slightly obscured	2	*
Opalescent areas, no details of iris visible, size of pupil barely discernible	3	*
Opaque cornea, iris not discernible through the opacity	4	*
(B) Area of cornea Involved:
One quarter (or less) but not zero	1
Greater than one-quarter, but less than one-half 2	2
Greater than one-half, but less than three-quarters 3	3
Greater than three quarters up to whole area 4	4
SCORE EQUALS A X B X 5      Maximum Total	80
(2) IRIS:
(A) Normal 0	0
Folds above normal, congestion, swelling, circumcorneal injection (any or all of these or combination of any thereof), iris still reacting to light (sluggish reaction is positive)	1	*
No reaction to light, hemorrhage, gross destruction (any or all of these)	2	*
SCORE EQUALS A X 5      Maximum Total	10
(3) CONJUNCTIVAE:
(A) REDNESS (refers to palpebral and bulbar conjunctivae excluding cornea & iris):
Blood vessels normal	0
Some blood vessels definitely hyperemic (injected)	1
More diffuse, deeper crimson red, individual vessels not easily discernible	2	*
Diffuse beefy red	3	*
(B) CHEMOSIS
No swelling	0
Any swelling above normal (includes nictitating membranes)	1
Obvious swelling with partial eversion of lids	2	*
Swelling with lids about half closed	3	*
Swelling with lids more than half closed	4	*
(C) DISCHARGE
No Discharge	0
Any amount different from normal (does not include small amounts observed in inner canthus of normal animals)	1
Discharge with moistening of the lids and hairs just adjacent to lids	2
Discharge with moistening of the lids and hairs and considerable area around the eye	3
SCORE EQUALS (A+B+C)x2      Maximum Total	20
The maximum total score is the sum of all scores obtained for the cornea, iris and conjunctivae.
*1ndicates a positive response

 

ULTRAVIOLET FLUORESCEIN SCAN SCORING CODE:

0= Negative

1 = Positive with an area 1/4 or less

2 = Positive with an area >1/4 but <1/2

3 = Positive with an area >1/2, but <3/4

4 = Positive with an area >3/4, up to entire area

Interpretation of results:

GHS criteria not met

Conclusions:

N-(4-(methoxybenzyl))-N,N-dimethylanilinium hexafluoroantimonate is an ocular irritant but not corrosive.

Executive summary:

There was no corneal opacity noted at any observation period although fluorescein stain retention was noted in one eye. Iritis was noted in one eye at 24 hours and cleared by 48 hours. Conjunctival irritation, noted in 3/3 eyes, cleared by day 7. There were no abnormal physical signs noted during the observation period.

Based on GHS/CLP, substances that produce in at least 2 of 3 tested animals a positive response of: corneal opacity ≥ 1; and/or iritis ≥ 1; and/ or conjunctival edema ≥ 2; and/or conjunctival chemosis ≥ 2, calculated as the mean scores, following grading at 24, 48, and 72 h and which fully reverses within 21 day shall be classified in Category 2. In only one animal, one of the above responses was observed and thus the substance does not meet the classification criteria.

N-(4-(methoxybenzyl))-N,N-dimethylanilinium hexafluoroantirronate is an ocular irritant but not corrosive. However, it does not meet the GHS/CLP criteria for classification.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Justification for classification or non-classification

The irritation and corrosion studies returned negative results and therefore the test substance is not classified.