Methyltrioctylammonium chloride

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

data is from authoritative database

Data source

Reference

Reference 1

Reference Type:

other: authoritative database

Title:

Acute dermal toxicity study of in rabbits

Author:

U.S. National Library of Medicine

Year:

2018

Bibliographic source:

Chemidplus Database,U.S. National Library of Medicine,2018

Reference 2

Reference Type:

other: authoritative database

Title:

Acute dermal toxicity study in rabbits

Author:

IFA GESTIS

Year:

2017

Bibliographic source:

Gestis Substance Database ,2017

Reference 3

Reference Type:

secondary source

Title:

Acute dermal ral toxicity study of test chemical was performed in rats.

Author:

NTRL

Year:

1992

Bibliographic source:

NTRL,1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Acute dermal toxicity study of test chemical was performed in rabbits.

GLP compliance:

not specified

Test type:

other: no data available

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Cetrimonium chloride

EC Number:

203-928-6

EC Name:

Cetrimonium chloride

Cas Number:

112-02-7

Molecular formula:

C19-H42-N.Cl

IUPAC Name:

N,N,N-trimethylhexadecan-1-aminium chloride

Details on test material:

- Name of test material (IUPAC name): 1-Hexadecanaminium, N,N,N-trimethyl-, chloride
- Common name: Trimethylhexadecylammonium chloride
- Molecular formula: C19H42ClN
- Molecular weight: 320.0008 g/mol
- Smiles notation: C(CCCCCCCCCCCCC)CC[N+](C)(C)C.[Cl-]
- InChl: 1S/C19H42N.ClH/c1-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20(2,3)4;/h5-19H2,1-4H3;1H/q+1;/p-1
- Substance type: Organic

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

Details on test animal
TEST ANIMALS
- Source: Pel neez Farms, Rogen,Arkansas,
- Weight at study initiation: 2.25 and 2.90 kilograms
- Housing: The animals were housed in a lamina air flow room in individual metal cages which were elevated above the droppings.
- Diet (e.g. ad libitum): Purino Rabbit Chow was provided ad libitum
- Water (e.g. ad libitum):water was provided ad libitum
- Acclimation period:14 days

IN-LIFE DATES: From: November 18, 1977 To: December 1, 1977

Administration / exposure

Type of coverage:

occlusive

Vehicle:

not specified

Details on dermal exposure:

TEST SITE
- Area of exposure: The test site was clipped with on Oster small animal clipper to the abraded skin of rabbits.
- % coverage: approximately 25% of the total body surface
- Type of wrap if used: The entire site was covered with a layer of 8-ply gauze, occluded with rubber dental dam and fastened with Johnson and Johnson Zanas porous tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): a wet disposable paper towel was used to remove residual test item.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4300 mg/kg bw

Duration of exposure:

24 hours

Doses:

4300 mg/kg bw

No. of animals per sex per dose:

Total:6 animals
4300 mg/kg bw: 3 male and 3 female

Control animals:

not specified

Details on study design:

Details on study design
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Statistics:

No data available

Results and discussion

Preliminary study:

No data available

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 300 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed at dose 4300 mg/kg bw

Mortality:

Rabbit No. 114-1-90M was found dead on Day 13, Rabbit No. 1143-975M was found dead on Day 8, and Rabbit No. 1143-979F was found dead on Day 5.

Clinical signs:

other: At the end of the 24-hour exposure period all animals exhibited normal behavior and appearance. On the 3rd day ,all rabbits exhibited depressed reflexes, body cold to touch, discharge from the eyes and nose, reddening of the eyes, eating and defecating ve

Gross pathology:

Necropsy findings in the animals which died included brown, liquid, fecal material around the anal area, bock legs and in colon, lungs adhered to chest wall, lungs white filled with white granular pockets and 9011 bladder enlarged in Rabbit No. 1143-90M; brownish or clear fluid around nose, mouth, chin and front limbs and no other visible lesions in Rabbit Nos. 1143-975M, and 1143-979F.At termination no visible lesion were noted when necropsies were performed on the surviving rabbits.

Other findings:

No data available

Any other information on results incl. tables

Table 1: Dosage Chart and Animal Weights for 1-Hexadecanaminium, N,N,N-trimethyl-, chloride ( 112-02-7).

Rabbit number	Total Volume Given (ml)	Initial Weight (kg)	Terminal Weight (kg)
1143-89M*	11.2	2.60	2.10
1143-90M	12.5	2.90	1.70**
1143-975M	9.7	2.25	1.35***
1143-976*	9.9	2.30	2.20
1143-979F*	11.4	2.65	1.70****
1143-112F	11.4	2.65	2.30

*abraded skin Dosage level 4300 mg/kg of animal body weight

** Died on Day 13

*** Died on Day 8

**** Died on Day 5

Applicant's summary and conclusion

Interpretation of results:

other: not classified

Conclusions:

The LD50 value was considered to be 4300 mg/kg bw,when group of 3 male and female New white Zealand rabbits were occlusively treated with test chemical by dermal application following 14 days of observation period.

Executive summary:

In acute dermal toxicity study,group of 3 male and female New white Zealand rabbits were treated with test chemical in the concentration of 4300 mg/kg bw by dermal application.The test site (approximately 25% of the total body surface) was clipped with on Oster small animal clipper 24 hours prior to application of the test material. The skin of one male and two females was abraded with the clipper head so as to penetrate the horny layer of the epidermis without causing bleeding. The skin of the remaining three rabbits was left intact.The entire site wascovered with a layer of 8-ply gauze, occluded with rubber dental dam and fastened with Johnson and Johnson Zanas porous tape.Each rabbit was restrained in a Newmann harness end returned to their cage for a 24-hour exposure period. At the end of the exposure period, the harness was removed from each rabbit, the occlusive wrap was removed, and any unabsorbed test material was wiped off with a wet disposable paper towel.Each rabbit was examined thoroughly for signs of systemic toxicity, changes in behavior, mortality and dermal irritation for 14 consecutive days foIIowing the day of dosage.After the 14-day observation period, the surviving animals were weighed, killed by an overdose of Beuthanasia D and necropsied to observe any internal gross effects. A gross necropsy was performed on each animal that died.Three of the six rabbits died during the study.At the end of the 24-hour exposure period all animals exhibited normal behavior and appearance.On the 3rd day ,all rabbits exhibited depressed reflexes, body cold to touch, discharge from the eyes and nose, reddening of the eyes, eating and defecating very little or none at all,and clear fluid around the nose, mouth, chin and front limbs.Rabbit Nos. 1143-975M and 1143-979F held their heads in a downward and tilting position and the nictitating membranes and eyelids appeared reddened. These signs persisted throughout the major portion of the study or until death occurred. Signs of skin irritation noted at the end of the 24-hour exposure period included slight to severe erythema, moderate or severe edema and whitening of the skin of the exposure area.The erythema remained relatively unchanged throughout the study while the edema subsided slightly. Also, moderate or severe atonia was noted on Day 3 through termination or until death Occurred, moderate or marked coriaceous skin from Day 2 through termination or until death in all rabbits; and fissuring in three rabbits and desquamation in one animal. All rabbits showed a substantial weight loss during the study. Necropsy findings in the animals which died included brown, liquid, fecal material around the anal area, bock legs and in colon, lungs adhered to chest wall, lungs white filled with white granular pockets and 9011 bladder enlarged in Rabbit No. 1143-90M; brownish or clear fluid around nose, mouth, chin and front limbs and no other visible lesions in Rabbit Nos. 1143-975M, and 1143-979F.At termination no visible lesion were noted when necropsies were performed on the surviving rabbits.Therefore, LD50 value was considered to be 4300 mg/kg bw,when rabbits were treated with test chemical by dermal applicationfollowing 14 days of observation period.