1-dodecylpyridinium chloride

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Data is from experimental study report.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

This study was designed to determine the dermal LD50 of the test item (up to 2000 mg/kg) or to establish a non-lethal dose level of 2000 milligram of test item per kilogram of body weight.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1-dodecylpyridinium chloride

EC Number:

203-232-2

EC Name:

1-dodecylpyridinium chloride

Cas Number:

104-74-5

Molecular formula:

C17H30N.Cl

IUPAC Name:

1-dodecylpyridin-1-ium chloride

Details on test material:

- Name of test material : 1-dodecylpyridinium chloride
- Molecular formula : C17H30N.Cl
- Molecular weight : 283.884 g/mol
- Physical state : Solid
- Substance type : Organic
- Smiles notation : [n+]1(ccccc1)CCCCCCCCCCCC.[ClH-]
- InChl : GKQHIYSTBXDYNQ-UHFFFAOYSA-M

SOURCE OF TEST MATERIAL
- Test Item: 1-dodecylpyridinium chloride (CAS No. 104-74-5)
- Source of test material: Sustainability Support Services (Europe) AB, Sweden
- Batch No. of test material: 6KBDG
- Manufacturing Date: May; 2017
- Expiration date of the lot/batch: April; 2018
- Consistency: Solid, powder

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Test Item and prepared formulation(s) were stored at ambient temperature.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test item was used as supplied by the Sponsor. Test item was grounded to fine powder prior to application. The particulates were moistened with distilled water before application.

FORM AS APPLIED IN THE TEST (if different from that of starting material) : paste

OTHER SPECIFICS:
Safety Precautions: Safety precautions included use of protective clothing, gloves, masks and eye protection (glasses).

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: National Institute of Biosciences, Pune.
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: Young adult female rats aged between 8 – 10 weeks were used.
- Weight at study initiation: The weight ranges of approximately 222.8 to 245.7 grams at initiation of dosing were used.
Body weights at the start : Female Mean: 235.02 g (= 100 %); Minimum : 222.8 g (- 5.20 %); Maximum : 245.7 g (+ 4.54 %)
-Identification: Each rat was individually identified by the cage number.
- 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): 19.2 to 21.8 degree centigrade.
- Humidity (%): 56.0% to 59.1%
- 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: 11-09-2017 to 28-12-2017

Administration / exposure

Type of coverage:

occlusive

Vehicle:

water

Remarks:

(Distilled water)

Details on dermal exposure:

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

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Distilled water was used to remove residual test item.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- For solids, paste formed: Yes

Duration of exposure:

24 hours

Doses:

Dose Range Finding Study:
Group I : 200 mg/kg body weight
Group I : 1000 mg/kg body weight
Group I : 2000 mg/kg body weight
Main Study:
Group II : 1000 mg/kg body weight

No. of animals per sex per dose:

Total No. of animals : 5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Twice daily
- Necropsy of survivors performed: Yes
- Other examinations performed: 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.

Statistics:

not specified

Results and discussion

Preliminary study:

Dose Range Finding Study: 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 revealed no clinical signs of toxicity or mortality during first 48 hours, hence, additional 1 female animal was administered at the dose of 2000 mg/kg body weight.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 1 000 mg/kg bw

Based on:

test mat.

Mortality:

Dose Range Finding Study:
Group I : Animal treated at the dose level of 200 mg/kg body weight survived through the study period of 14 days.
Group I : Animal treated at the dose level of 1000 mg/kg body weight survived through the study period of 14 days.
Group I : Animal treated at the dose level of 2000 mg/kg body weight found dead on day 1.
Main Study:
Group II : Animals treated at the dose level of 1000 mg/kg body weight survived through the study period of 14 days.

Clinical signs:

other: 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. Group I : Animal treated at the dose level of 1000 mg/kg body weight did not result

Gross pathology:

Gross pathological examination did not reveal any abnormalities attributable to the treatment in animals from 200 mg/kg dose group whereas gross pathological examination revealed moderate to severe erythema on site of application in animals from 1000 mg/kg dose group from dose range finding study and main study sacrificed terminally.

Other findings:

Evaluation of Dermal Reaction
Dose Range Finding Study:
Group I : Animal treated at the dose level of 200 mg/kg body weight did not result in any skin reaction during the study period of 14 days.
Group I : Animal treated at the dose level of 1000 mg/kg body weight resulted in minimal to moderate erythema at the site of application from day 1 to day 14.
Main Study:
Group II : Animal treated at the dose level of 1000 mg/kg body weight resulted in minimal to moderate erythema at the site of application from day 1 to day 14.

Any other information on results incl. tables

Table No. I

Summary of Clinical Signs of Toxicity and Mortality

Laboratory Test Item Code :TAS/122/054

Test System : Sprague Dawley Rat

Sex : Female

Dose Finding Study:

Group  No.	Dose mg/kg	Observed Signs	Total Number of Animals	Animal No.	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 No.	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 No.	Period of signs in days  From - to	Mortality
I	2000	Found dead	1	3	Day 1	1/1

 

Main Study:

Group  No.	Dose mg/kg	Observed Signs	Total Number of Animals	Animal Nos.	Period of signs in days  From - to	Mortality
II	1000	No clinical signs observed	2	4, 5	Day 0 - Day 14	0/2

Table No. II

Summary of Evaluation of Dermal Reaction

Laboratory Test Item Code :TAS/122/054

Test System : Sprague Dawley Rat

Sex : Female

DoseFinding Study:

Group  No.	Dose mg/kg	Dermal Reaction	Total Number of Animals	Animal No.	Period of signs in days  From - to
I	200	No dermal reaction observed	1	1	Day 0 - Day 14

 

Group  No.	Dose mg/kg	Dermal Reaction	Total Number of Animals	Animal No.	Period of signs in days  From - to
I	1000	Minimal to moderate erythema	1	2	Day 1 - Day 14

 

Main Study:

Group  No.	Dose mg/kg	Dermal Reaction	Total Number of Animals	Animal Nos.	Period of signs in days  From - to
II	1000	Minimal to moderate erythema	2	4, 5	Day 1 – Day 14

 

Table No.III

Mean Body Weight and Percent Body Weight Gain (g)

Laboratory Test Item Code :TAS/122/054

Test System : Sprague Dawley Rat

Sex : Female

DoseFinding 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	226.0	241.6	6.90	252.6	4.55	11.77
		± 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	235.1	248.8	5.83	257.4	3.46	9.49
		± 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	222.8	-	-	-	-	-
		± 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	1000	Mean	245.60	255.65	4.09	264.85	3.60	7.84
		± SD	0.14	1.34	0.61	0.78	0.24	0.38

Table No.IV

Summary of Gross Pathological Findings

Laboratory Test Item Code :TAS/122/054

Test System : Sprague Dawley Rat

Sex : Female

DoseFinding Study:

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

 

Group No.	Dose mg/kg	Animal Number	Animal Fate	Gross Pathological Findings
I	1000	2	TS	Moderate to severe erythema was observed on site of application

 

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

 

                    Main Study:

Group No.	Dose mg/kg	Animal Numbers	Animal Fate	Gross Pathological Findings
II	1000	4, 5	TS	Moderate to severe erythema was observed on site of application

 

                     FD = Found dead

         TS = Terminal sacrifice

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

It was concluded that the acute dermal median lethal dose (LD50) of the given test chemical, when administered to female Sprague Dawley rats was considered to be >1000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that the given test chemical can be classified as an acute dermal toxicant. CLP Classification: “Category 4 (>1000-2000 mg/kg bw)”.

Executive summary:

The reported study was designed and conducted to determine the acute dermal toxicity profile of the given test chemical as per OECD Guideline 402 (Acute Dermal Toxicity) in Sprague Dawley rats.

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 revealed no clinical signs of toxicity or mortality 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 resulted in mortality on day 1. As the dose range finding study revealed mortality at the maximum dose of 2000 mg/kg, the main study was initiated with two additional animals at a dose of 1000 mg/kg body weight. The animals were administered with a dose of 1000 mg/kg body weight in sequential manner at 48 hours intervals.

Administration of 200 mg/kg body weight exhibited normal body weight gain and no clinical signs of toxicity during the study period of 14 days. Administration of 1000 mg/kg body weight revealed minimal to moderate erythema at the site of application from day 1 to day 14 and exhibited normal body weight gain, no clinical signs of toxicity or mortality during the study period of 14 days from dose range finding study and main study. Gross pathological examination did not reveal any abnormalities attributable to the treatment in animals from 200 mg/kg dose group whereas gross pathological examination revealed moderate to severe erythema on site of application in animals from 1000 mg/kg dose group.

It was concluded that the acute dermal median lethal dose (LD50) of the given test chemical, when administered to female Sprague Dawley rats was considered to be >1000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that the given test chemical can be classified as an acute dermal toxicant. CLP Classification: “Category 4 (>1000-2000 mg/kg bw)”.