Quaternary ammonium compounds, di-C8-10-alkyldimethyl, chlorides

Acute Toxicity: dermal

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Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

3rd March 1987 - 17th March 1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

The dosages were changed to: Group Treatment Level (mg/kg bw) 1 552 2 1104 3 3328 4 4448

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test material form:

liquid

Specific details on test material used for the study:

Substance was stored at room temperature at all times.

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Housing: Suspended stainless steel wire mesh bottom cages.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days prior to initiation of study.

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

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: 10% v/v solution of ethanol/water.

Details on dermal exposure:

On the day prior to dosing, the fur was clipped from the dorsal area of the trunk of each rabbit. The exposed area on the trunk of each animal measured approximately 12x20 cm and constitutred 10% of the animal's total body surface. On the following day, the appropriate material was applied uniformly over the exposed skin, or as much of the area as possible. An occlusive binder was secured around the trunk of each animal immediately after treatment.

Duration of exposure:

24 hours.

Doses:

552, 1104, 3328 or 4448 mg/kg bw.

No. of animals per sex per dose:

Five/sex/dose

Control animals:

yes, concurrent vehicle

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 until day 15. Particular attention was given to observations of tremours, convulsions, seizures, lethargy and other signs of cardiac and/or central nervous system toxicity. Individual body weights were determined on days 1, 8 and 15 or at death.
- Necropsy of survivors performed: yes. Animals which died during the study were also subjected to a gross necropsy examination at the time of death or when found dead. During necropsy examinations, particular attention was directed to abnormalities of the heart and its auxialiary vascular system.

Statistics:

LD50 was calculated using the Probit Analysis method.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

3 861 mg/kg bw

Based on:

test mat.

95% CL:

> 0 - < 4 292

Mortality:

Individual mortality data is presented below in the table.
No deaths occurred among the vehicle control animals.

Clinical signs:

No clinical effects related to the treatment with the vehicle were noted.
The substance was irritating to the skin in all animals at all doses, these effects were characterised by eschar formation at the treatment sites within 24 hours after administration.Adverse effects were first noted at the 1104 mg/kg bw group when compared to controls. Reduced faecal production was present throughout the test population within 72 hours post administration and lasted for 1 to 4 days. One animal also displayed decreased activity, nasal discharge, mucoid excretions, an apparent bloody snout, faecal stains of the haircoat and soft stools. A second animal from this dose level displayed mucoid excretions and nasal discharge. In the higher dose levels these effects were more prevalent and the reduced faecal production was extended in duration. These events were often accompanied by emaciation and late deaths. Decreased activity was more prevalent in all animals and random but significant clinical findings included prostration, ataxia, tremours, laboured breathing and mucoid excretions. Isolated findings in one to three animals included nasal discharge, apparent bloody snouts, rales, soft stools, faecal/urine stains of the haircoat and anogenital areas.

Body weight:

A decrease in mean body weight was observed in all treatment groups in a dose response relationship. At the lowest level a minimal weigh loss (3-127 g) was observed in some 70% animals on day 8. The weight loss was a transient event and recovery to control levels was observed by day 15. At increasing dose levels, the incidence of weight loss within each test population, the amount of weight loss and the delayed recovery to control levels increased. At 1104 mg/kkg bw dose level the weight lost between days 1 and 8 was only partially recovered by day 15. At the two higher dose levels, the weight loss persisted in survivors.
By contrast, the mean body weight of male and female vehicle control animals increased at each measurement interval.

Gross pathology:

Gross necropsy findings were minimal. There was an increased incidence of pale kidneys in animals at the highest treatment level as compared to controls.Distended atria and/or ventricles were also noted in three animals at the highest dose levels.One animal in the 3328 mg/kg bw treatment group was noted to have a heavily pigmented gel in the large intestine.

Any other information on results incl. tables

Mortality data:

Treatment	Dose level	No. of Deaths/No. Dosed
		Males	Females	Sexes Combined
10% Ethanol/Water	5.56 ml/kg bw	0/5	0/5	0/10
Substance (80% active)	552 mg/kg bw	0/5	0/5	0/10
	1104 mg/kg bw	0/5	0/5	0/10
	3328 mg/kg bw	3/5	2/5	5/10
	4448 mg/kg bw	5/5	3/5	8/10

Applicant's summary and conclusion

Conclusions:

The acute dermal toxicity of the substance is 3342 mg/kg bw in the rabbit. The substance was a corrosive as evidenced by adverse signs at the site of application.

Executive summary:

In an acute dermal toxicity study an 80% solution of the substance was administered to New Zealand White rabbits (5 animals/sex/dose) by occlusive dressing at a dose levels of 552, 1104, 3328 or 4448 mg/kg bw (single administration). The exposure was for 24 hours after which the animals were observed for 14 days and observed for mortlaity, signs of clinical toxicity, changes to body weight gain and gross pathology was conduted at necropsy. There was dose-dependent mortalities and signs of clinical toxicity. A decrease in mean body weight was observed in all treatment groups in a dose response relationship. Gross necropsy findings were minimal. There was an increased incidence of pale kidneys in animals at the highest treatment level as compared to controls.Distended atria and/or ventricles were also noted in three animals at the highest dose levels.One animal in the 3328 mg/kg bw treatment group was noted to have a heavily pigmented gel in the large intestine. The acute dermal toxicity of the substance is 3342 mg/kg bw in the rabbit. The substance was a corrosive as evidenced by adverse signs at the site of application.

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