Dimethyldioctylammonium chloride

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

3rd March 1987 - 17th March 1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

- Principle of test: to assess the short term toxicity of a test article in rabbits when administered by the dermal route.
- Short description of test conditions: The animals were acclimitised for 5 days prior to treatment. The fur from the dorsal area of the trunk of the test animals was clipped on the day of treatment. The substance was applied uniformly over the clipped area and held in contact with the skin for a 24 hour exposure period using gauze. Residual substance will be removed following the the exposure period using water (if possible).
- Parameters analysed / observed: Bodyweight, mortality, toxic effects, cage side effects (skin, fur, eyes, mucous membranes, respiratory, circulatory automic and central nervous system, somato-motor activity and behaviour patterns). Upon necropsy gross pathology examinations.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyldioctylammonium chloride

EC Number:

226-901-0

EC Name:

Dimethyldioctylammonium chloride

Cas Number:

5538-94-3

Molecular formula:

C18H40NCl

IUPAC Name:

dimethyldioctylazanium chloride

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Sponsor provided the substance.

STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing:
- Final dilution of a dissolved solid, stock liquid or gel: The volume of liquid product administered to each animal was adjusted based on the stated 80% activity of the material to achieve the speific treatment level.

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Gota-Frisco Farms, Edon, OH (USA)
- Females (if applicable) nulliparous and non-pregnant:not specified
- Weight at study initiation: 2.704 to 2.745 kg
- Housing: Housed individually in suspended stainless steel cages.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

ethanol

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorsal area of the trunk
- % coverage: 10% of the animal's total body surface.
- Type of wrap if used: A layer of 8 ply gauze dressing, a lyer of rubber dam and several wrappings of 3 inch Elastoplast tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with water.
- Time after start of exposure: 24 hours after treatment.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.06, 0.2, 0.42 or 0.83 ml/kg bw
- Concentration (if solution): 8, 160, 336 or 664 mg/kg bw
- Constant volume or concentration used: not specified

Duration of exposure:

24 hours.

Doses:

8, 160, 336 or 664 mg/kg bw

No. of animals per sex per dose:

5 animals/sex/dose

Control animals:

yes, concurrent vehicle

Remarks:

10% v/v denat. ethanol in water

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed for mortality and toxic effects for 8 hours after dosing and daily thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, gross pathology.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

259 mg/kg bw

Based on:

test mat.

95% CL:

> 82 - <= 639

Mortality:

No deaths occurred in the vehicle control animals and in the 8 mg/kg bw group (lowest dose).
In the 160 mg/kkg bw group 4 out of 10 animals had died.
In the 336 mg/kkg bw group 6 out of 10 animals had died.
In the 664 mg/kkg bw group 7 out of 10 animals had died.

Clinical signs:

other: The substance produced significant dermal irritation in the animals which was characterised by eschar formation at the treatment site. In all animals, eschar formation was evident by the day following dose administration. A dose-response related incidence

Gross pathology:

There were a number of gross pathologic findings reported throughout both the test and control groups with no apparent dose-response relationship. The findings in the dead animals could be an artefact of post-mortem changes, such as increased incidence of colour changes in kidneys and lungs. There was a single animal with white material in the lungs from a treatment group, this was atributed to pulmonary infection in this rabbit. Cardiac anomalies was noted in several animals from the treatment groups with no apparent dose-response relationship.

Any other information on results incl. tables

Treatment	Dose	No. of Deaths/No. Dosed
		Males	Females	Sexes Combined
10% Ethanol/Water	5.6 ml/kg bw	0/5	0/5	0/10
Substance	8 mg/kg bw	0/5	0/5	0/10
	160 mg/kg bw	2/5	2/5	4/10
	336 mg/kg bw	3/5	3/5	6/10
	664 mg/kg bw	4/5	3/5	7/10

Clinical Finding(s)	Incidence of Finding in Treatment Groups
	Vehicle Control	8 mg/kg bw	160 mg/kg bw	336 mg/kg bw	664 mg/kg bw
Soft stools and/or faecal stain	1/10	-	-	1/10	1/10
Few faeces	1/10	4/10	6/10	8/10	4/10
Laboured breathing	-	-	-	1/10	2/10
Prostration	-	-	-	-	1/10
Nasal discharge	-	1/10	-	-	-
Activity decreased	-	1/10	2/10	3/10	5/10
Tremors	-	-	-	-	2/10
Ataxia	-	-	-	1/10	-

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The dermal LD50 in rabbits is 259 mg/kg bw. Based on the observations the substance is considered to be corrosive to the skin and toxic by the dermal route as established by the LD50.

Executive summary:

In an acute dermal toxicity study an 80% solution of the substance was administered to rabbits (5 animals/sex/dose) by dermal administration at dose levels of 8, 160, 336 or 664 mg/kg bw (single administration) for a duration of 24 hours. A number of animals died in the top 3 dose groups and clinical toxicity was observed in the treatment animals, this included significant dermal irritation characterised by eschar formation at the treatment site. In all animals, eschar formation was evident by the day following dose administration. A dose-response related incidence of clinical effects included reduced faeces, laboured breathing and decreased activity. Prostration, nasal discharge, tremors and ataxia was observed in the top dose only. Mean body weights in the top 3 dose groups was reduced, but generally a partial or complete recovery of body weights was observed in the majority of animals that survived to termination. The dermal LD50 in rabbits is 259 mg/kg bw.