Methyltrioctylammonium chloride

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Justification for type of information:

data is from experimental reports

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

To determine the dermal reaction profile of Methyltrioctylammonium chloride in Sprague Dawley rats

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Methyltrioctylammonium chloride

EC Number:

225-896-2

EC Name:

Methyltrioctylammonium chloride

Cas Number:

5137-55-3

Molecular formula:

C25H54ClN

IUPAC Name:

methyltrioctylammonium chloride

Test material form:

liquid: viscous

Details on test material:

- Name of test material: Methyltrioctylammonium chloride
- IUPAC name: Methyltrioctyl ammonium chloride
- Molecular formula: C25H54ClN
- Molecular weight: 404.162 g/mole
- Smiles :[N+](CCCCCCCC)(CCCCCCCC)(CCCCCCCC)C.[ClH-]
- Inchl: 1S/C25H54N.ClH/c1-5-8-11-14-17-20-23-26(4,24-21-18-15-12-9-6-2)25-22-19-16-13-10-7-3;/h5-25H2,1-4H3;1H/q+1;/p-1
- Substance type: Organic
- Physical state: Viscous liquid (yellow to yellowish brown)
- Purity: not less than 90.0%

Specific details on test material used for the study:

- Name of test material: Methyltrioctylammonium chloride
- IUPAC name: Methyltrioctyl ammonium chloride
- Molecular formula: C25H54ClN
- Molecular weight: 404.162 g/mole
- Smiles :[N+](CCCCCCCC)(CCCCCCCC)(CCCCCCCC)C.[ClH-]
- Inchl: 1S/C25H54N.ClH/c1-5-8-11-14-17-20-23-26(4,24-21-18-15-12-9-6-2)25-22-19-16-13-10-7-3;/h5-25H2,1-4H3;1H/q+1;/p-1
- Substance type: Organic
- Physical state: Viscous liquid (yellow to yellowish brown)
- Manufacturing Date: 1-8-2017
- Expiry Date : 1-7-2020
- Consistency: Liquid
- Batch Number: 217MAU0019
- Safety Precautions: Safety precautions included use of protective clothing, gloves, masks and eye protection (glasses).
- Storage Condition: Ambient Temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Sex: female
- Source: National Institute of Biosciences, Pune.
- Females nulliparous and non-pregnant: Females were nulliparous and non-pregnant
- Age at study initiation: Young adult (8 to 10 weeks old) female rats were used.
- Weight at study initiation: The weight range of approximately 221.6 to 235.3 grams at initiation of dosing
Body weights at the start :
Female
Mean : 226.90 g (= 100 %)
Minimum : 221.6 g (- 2.34 %)
Maximum : 235.3 g (+ 3.70 %)
Total No. of animals : 5
- Identification: Each rat was individually identified by the cage number.
- Fasting period before study: No data available
- Housing: The rats were individually housed in polycarbonate cages with paddy husk as bedding.
- Diet (e.g. ad libitum): Rodent feed supplied by the Nutrivet Life Sciences, Pune, was provided ad libitum from individual feeders.
- Water (e.g. ad libitum): Water was provided ad libitum from individual bottles attached to the cages. All water was from a local source and passed through the reverse osmosis membrane before use.
- Acclimation period: 5 days.

ENVIRONMENTAL CONDITIONS

Temperature (°C): 19.0 to 22.5 degree centigrade
- Humidity (%): 55.3% to 58.8%.
- Air changes (per hr): Ten to fifteen air changes per hour.
- Photoperiod (hrs dark / hrs light): An artificial light and dark cycle of 12 hours each was provided to the room.

IN-LIFE DATES: Experimental Starting Date: 06-03-2018
Experimental Completion Date: 29-03-2018

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

Dose range finding study: 200, 1000, 2000 mg/kg
Main study: 2000 mg/kg

Duration of treatment / exposure:

24 hours

Observation period:

14 days

Number of animals:

Dose Range Finding Study: 3
Main Study: 2

Details on study design:

TEST SITE
- Area of exposure: Trunk (dorsal surface and sides from scapular to pelvic area)
- % coverage: Approximately 10% of the body surface area.
- Type of wrap if used: Porous gauze dressing and non-irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure:Following 24 hours of exposure, the wrapping was removed and the test site wiped free of excess test item. Distilled water was used to remove residual test item.

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) : Dermal reaction was observed daily for study period of 14 days.

SCORING SYSTEM: Draize Method

OTHER OBSERVATIONS

Viability: Twice daily.

Clinical Observations and General Appearance: Animals were observed for clinical signs, mortality, until sacrifice. Onset, duration and severity of any sign were recorded. The clinical signs and mortality observations were conducted at 10, 30, 60 minutes, 2, 4 and 6 hours on the day of dosing and once daily thereafter for 14 day. Daily observation was done as far as possible at the same time.The observations included general clinical signs, observations of eyes, mucous membranes, respiratory, circulatory system and behavior pattern.

Evaluation of Dermal Reaction: Dermal reaction was observed daily for study period of 14 days.

Body weights: Individual animal body weights were recorded pre-test (prior to administration of the test item), day 7 and at termination on day 14.

Gross Pathology: Necropsy was performed on animals surviving at the end of the study. Macroscopic examination of all the orifices, cavities and tissues were made and the findings were recorded. All animals surviving the study period were sacrificed by the carbon dioxide asphyxiation technique (day 15).

Histopathology: No gross abnormalities were observed in animals sacrificed terminally hence, no histopathology was performed.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: #1,#2,#3

Time point:

other: 11 days

Score:

1

Reversibility:

fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Remarks:

dose range finding study

Results 2

Irritation parameter:

edema score

Basis:

animal: #1, #2,#3

Time point:

other: 11 days

Score:

1

Reversibility:

fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Remarks:

dose range finding study

Results 3

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

other: 12 days

Score:

1

Reversibility:

fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Remarks:

main study

Results 4

Irritation parameter:

edema score

Basis:

animal #4

Time point:

other: 10 days

Score:

1

Reversibility:

fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Results 5

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

other: 13 days

Score:

1

Reversibility:

fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Results 6

Irritation parameter:

edema score

Basis:

animal #5

Time point:

other: 12 days

Score:

1

Reversibility:

fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

Dose Range Finding Study:
Group I : Animal treated at the dose level of 200 mg/kg body weight resulted in slight to moderate oedema, thickening of skin, desquamation and slight to moderate erythema at the site of application. The site of application was free of any skin reaction at the termination of study period.
Group I : Animal treated at the dose level of 1000 mg/kg body weight resulted in slight to severe oedema, thickening of skin, desquamation and slight to severe erythema at the site of application. The site of application was free of any skin reaction at the termination of study period.
Group I : Animal treated at the dose level of 2000 mg/kg body weight resulted in slight to severe oedema, thickening of skin, desquamation and slight to severe erythema at the site of application. The site of application was free of any skin reaction at the termination of study period
Main Study:
Group II : Animals treated at the dose level of 2000 mg/kg body weight resulted in slight to severe oedema, thickening of skin, desquamation and slight to severe erythema at the site of application. The site of application was free of any skin reaction at the termination of study period.

Other effects:

Clinical Signs of Toxicity and Mortality:
Sex : Female
Dose Range Finding Study:
Group I : Animal treated at the dose level of 200 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days. The animal survived through the study period of 14 days.
Group I : Animal treated at the dose level of 1000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days. The animal survived through the study period of 14 days.
Group I : Animal treated at the dose level of 2000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days. The animal survived through the study period of 14 days.
Main Study:
Group II : Animals treated at the dose level of 2000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days. All animals survived through the study period of 14 days.
Body Weight:
Sex : Female
Dose Range Finding Study:
Group I (200 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 5.46% and 8.48% respectively.
Group I (1000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 5.18% and 7.28% respectively.
Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 4.74% and 10.56% respectively.
Main Study:
Group II (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 3.38% and 6.47% respectively.
Gross Pathological Findings :
Gross pathological examination did not reveal any abnormalities in animals from 200 mg/kg, 1000 mg/kg and 2000 mg/kg dose groups from dose range finding study and main study sacrificed terminally.

Any other information on results incl. tables

Summary of Evaluation of Dermal Reaction

 

Laboratory Test Item Code :TAS/122/068

Test System : Sprague Dawley Rat

Sex : Female

Finding Study:

Group  No.	Dose mg/kg	Total Number of Animals	Animal Nos.	Dermal Reaction	Period of signs in days  From – to	Period of signs in days  From – to
I	200	1	1	Erythema	Slight	Day 10 – Day 11
					Moderate	Day 8 – Day 9
				Oedema	Slight	Day 3, Day 8 – Day 10
					Moderate	Day 4
					Severe	Day 5
				Thickening of skin	-	Day 2 - Day 6
				Desquamation	-	Day 6 - Day 7

 

Group  No.	Dose mg/kg	Total Number of Animals	Animal Nos.	Dermal Reaction	Period of signs in days  From – to	Period of signs in days  From – to
I	1000	1	2	Erythema	Slight	Day 11 – Day 12
					Moderate	Day 9 – Day 10
					Severe	Day 8
				Oedema	Slight	Day 2, Day 8 – Day 11
					Moderate	Day 3
					Severe	Day 4 – Day 5
				Thickening of skin	-	Day 2 - Day 6
				Desquamation	-	Day 6 - Day 7

 

Group  No.	Dose mg/kg	Total Number of Animals	Animal Nos.	Dermal Reaction	Period of signs in days  From – to	Period of signs in days  From – to
I	2000	1	3	Erythema	Slight	Day 11 – Day 13
					Moderate	Day 9 – Day 10
					Severe	Day 7 – Day 8
				Oedema	Slight	Day 7 – Day 11
					Moderate	Day 3
					Severe	Day 4 – Day 5
				Thickening of skin	-	Day 1 - Day 5
				Desquamation	-	Day 6

 

Main Study:

Group  No.	Dose mg/kg	Total Number of Animals	Animal Nos.	Dermal Reaction	Period of signs in days  From – to	Period of signs in days  From – to
II	2000	1	4	Erythema	Slight	Day 11 – Day 12
					Moderate	Day 10
					Severe	Day 8 – Day 9
				Oedema	Slight	Day 8 – Day 10
					Moderate	Day 3
					Severe	Day 4 – Day 6
				Thickening of skin	-	Day 1 - Day 6
				Desquamation	-	Day 7

 

Group  No.	Dose mg/kg	Total Number of Animals	Animal Nos.	Dermal Reaction	Period of signs in days  From – to	Period of signs in days  From – to
II	2000	1	5	Erythema	Slight	Day 12 – Day 13
					Moderate	Day 9 – Day 11
					Severe	Day 7 – Day 8
				Oedema	Slight	Day 7 – Day 12
					Moderate	Day 1 – Day 2
					Severe	Day 3 – Day 5
				Thickening of skin	-	Day 1 - Day 5
				Desquamation	-	Day 6

 

 

 

Individual Animal - Evaluation of Dermal Reaction

 

Laboratory Test Item Code :TAS/122/068

Test System : Sprague Dawley Rat

Sex : Female  

Finding Study:

Group : I                                                                      Dose  : 200 mg/kg body weight

Animal	Dermal	D A Y S
No.	Reaction	0	1	2*	3*	4*	5*	6*	7	8	9	10	11	12	13	14
1	Erythema	0	0	0	0	0	0	D	D	2	2	1	1	0	0	0
	Oedema	0	0	0	1	2	3	D	D	1	1	1	0	0	0	0

 

Group : I                                                                    Dose  : 1000 mg/kg body weight

Animal	Dermal	D A Y S
No.	Reaction	0	1	2*	3*	4*	5*	6*	7	8	9	10	11	12	13	14
2	Erythema	0	0	0	0	0	0	D	D	3	2	2	1	1	0	0
	Oedema	0	0	1	2	3	3	D	D	1	1	1	1	0	0	0

 

Group : I                                                                    Dose  : 2000 mg/kg body weight

Animal	Dermal	D A Y S
No.	Reaction	0	1*	2*	3*	4*	5*	6	7	8	9	10	11	12	13	14
3	Erythema	0	0	0	0	0	0	D	3	3	2	2	1	1	1	0
	Oedema	0	0	0	2	3	3	D	1	1	1	1	1	0	0	0

 

Main Study:

Group : II                                                                   Dose  : 2000 mg/kg body weight

Animal	Dermal	D A Y S
No.	Reaction	0	1*	2*	3*	4*	5*	6*	7	8	9	10	11	12	13	14
4	Erythema	0	0	0	0	0	0	0	D	3	3	2	1	1	0	0
	Oedema	0	0	0	2	3	3	3	D	1	1	1	0	0	0	0

 

Animal	Dermal	D A Y S
No.	Reaction	0	1*	2*	3*	4*	5*	6	7	8	9	10	11	12	13	14
5	Erythema	0	0	0	0	0	0	D	3	3	2	2	2	1	1	0
	Oedema	0	2	2	3	3	3	D	1	1	1	1	1	1	0	0

 

* = Thickening of skin

D = Desquamation

Summary of Clinical Signs of Toxicity and Mortality

 

Finding Study:

Group  No.	Dose mg/kg	Observed Signs	Total Number of Animals	Animal Nos.	Period of signs in days  From - to	Mortality
I	200	No clinical signs observed	1	1	Day 0 - Day 14	0/1

 

Group  No.	Dose mg/kg	Observed Signs	Total Number of Animals	Animal Nos.	Period of signs in days  From - to	Mortality
I	1000	No clinical signs observed	1	2	Day 0 - Day 14	0/1

 

Group  No.	Dose mg/kg	Observed Signs	Total Number of Animals	Animal Nos.	Period of signs in days  From - to	Mortality
I	2000	No clinical signs observed	1	3	Day 0 - Day 14	0/1

 

Main Study:

Group  No.	Dose mg/kg	Observed Signs	Total Number of Animals	Animal Nos.	Period of signs in days  From - to	Mortality
II	2000	No clinical signs observed	2	4, 5	Day 0 - Day 14	0/2

Mean Body Weight and Percent Body Weight Gain (g)

 

Finding Study:

Group No.	Dose (mg/kg body weight)		Body weight Day 0	Body weight Day 7	% body weight gain day 0-7	Body weight Day 14	% body weight gain day 7- 14	% body weight gain day 0- 14
I	200	Mean	221.6	233.7	5.46	240.4	2.87	8.48
		± SD	-	-	-	-	-	-

 

Group No.	Dose (mg/kg body weight)		Body weight Day 0	Body weight Day 7	% body weight gain day 0-7	Body weight Day 14	% body weight gain day 7- 14	% body weight gain day 0- 14
I	1000	Mean	223.8	235.4	5.18	240.1	2.00	7.28
		± SD	-	-	-	-	-	-

 

Group No.	Dose (mg/kg body weight)		Body weight Day 0	Body weight Day 7	% body weight gain day 0-7	Body weight Day 14	% body weight gain day 7- 14	% body weight gain day 0- 14
I	2000	Mean	223.5	234.1	4.74	247.1	5.55	10.56
		± SD	-	-	-	-	-	-

 

Main Study:

Group No.	Dose (mg/kg body weight)		Body weight Day 0	Body weight Day 7	% body weight gain day 0-7	Body weight Day 14	% body weight gain day 7- 14	% body weight gain day 0- 14
II	2000	Mean	232.80	240.65	3.38	247.85	2.99	6.47
		± SD	3.54	1.91	0.75	2.33	0.15	0.61

Summary of Gross Pathological Findings

Finding Study:

Group No.	Dose mg/kg	Animal Numbers	Animal Fate	Gross Pathological Findings
I	200	1	TS	No abnormality detected

 

Group No.	Dose mg/kg	Animal Numbers	Animal Fate	Gross Pathological Findings
I	1000	2	TS	No abnormality detected

 

Group No.	Dose mg/kg	Animal Numbers	Animal Fate	Gross Pathological Findings
I	2000	3	TS	No abnormality detected

 

                    Main Study:

Group No.	Dose mg/kg	Animal Numbers	Animal Fate	Gross Pathological Findings
II	2000	4, 5	TS	No abnormality detected

 

                     TS = Terminal Sacrifice

Applicant's summary and conclusion

Interpretation of results:

Category 1 (corrosive) based on GHS criteria

Conclusions:

Slight to severe oedema, thickening of skin followed by desquamation resulting in slight to severe erythema at the site of application was observed in all animals from dose range finding study.Slight to severe oedema, thickening of skin followed by desquamation resulting in slight to severe erythema at the site of application was observed in all animals from main study. The site of application was free of any skin reaction at the termination of study period.
Eventhough the effects were reversible till 14 days, since they were observed in all the tested animals, Methyltrioctylammonium chloride can be considered to be corrosive to skin.
It can be further classified under the category "Category 1" as per CLP regulation.

Executive summary:

A study was designed and conducted to determine the acute dermal toxicity profile of Methyltrioctylammonium chloride (CAS No. 5137-55-3)in Sprague Dawley rats. 5 Young adult (8 to 10 weeks old) female Sprague Dawley rats were used for the study.

Approximately 24 hours before application, the hair of each rat was closely clipped from the trunk (dorsal surface and sides from scapular to pelvic area) with an electric clipper, so as to expose at least 10% of the body surface area.

The test item was applied directly onto the exposed skin of the animal, taking care to spread the test item evenly over the entire area of approximately 10% of the total body surface area or as much of the area as can reasonably be covered. The test item was held in contact with the skin using a porous gauze dressing and non irritating tape around the animal to cover the exposure site for first 24 hours exposure period. Elizabethan collar was placed on each animal for first 24 hours after application of the test item. These collars prevent ingestion of test item.

Following 24 hours of exposure, the wrapping was removed and the test site wiped free of excess test item. Distilled water was used to remove residual test item.

In the dose range finding study a single dose of 200 mg/kg body weight of the test item was administered to 1 female animal. No death or clinical signs of toxicity was observed during first 48 hours, hence, additional 1 female animal was administered with the dose of 1000 mg/kg body weight. Administration of 1000 mg/kg body weight did not reveal any clinical signs of toxicity or death during first 48 hours, hence, additional 1 female animal was administered at the dose of 2000 mg/kg body weight. Administration of 2000 mg/kg body weight did not reveal any clinical signs of toxicity or death during first 48 hours.

Animals from dose range finding study treated at the dose levels of 200 mg/kg, 1000 mg/kg and 2000 mg/kg exhibited normal body weight gain and no clinical signs of toxicity or mortality during the study period of 14 days. As the dose range finding study revealed no mortality or clinical signs at the maximum dose of 2000 mg/kg, hence, the main study was initiated with two additional animals. The animals were administered with a dose of 2000 mg/kg body weight in sequential manner at 48 hours intervals.

Animals from main study treated at the dose level of 2000 mg/kg exhibited normal body weight gain and no clinical signs of toxicity or mortality during the study period of 14 days.

Gross pathological examination did not reveal any abnormalities attributable to the treatment.

Slight to severe oedema, thickening of skin followed by desquamation resulting in slight to severe erythema at the site of application was observed in all animals from dose range finding study.Slight to severe oedema, thickening of skin followed by desquamation resulting in slight to severe erythema at the site of application was observed in all animals from main study.  The site of application was free of any skin reaction at the termination of study period.

Eventhough the effects were reversible till 14 days, since they were observed in all the tested animals, Methyltrioctylammonium chloride can be considered to be corrosive to skin.

It can be further classified under the category "Category 1" as per CLP regulation.