Reaction mass of bis(N-decyl-N,N-dimethyldecan-1-aminium) carbonate and N-decyl-N,N-dimethyldecan-1-aminium hydrogen carbonate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes (incl. QA statement)

Remarks:

Safepharm Laboratories Ltd

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Test material form:

other: solid gel

Details on test material:

- Name of test material: Didecyldimethylammonium carbonate

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

On receipt the animals were randomly allocated to cages. The female was nulliparous and non-pregnant. After an acclimatisation period of at least five days the animals were selected at random and given a number unique within the study by a number written on a cage card. At the start of the study the animals weighed at least 200g, and were eight to twelve weeks of age.
The animals were housed in suspended solid-floor polypropylene cages furnished with woodflakes. The animals were housed individually. Free access to mains drinking water and food (Certified Rat and Mouse Diet (Code 5LF2) supplied by BCM IPS Limited, London, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70 % respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

IN-LIFE DATES: 09 June 2004 and 10 June 2004

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The study was performed to assess the dermal toxicity of the test material in the rat. Two animals (one male and one female) were given a single, 24 hour, semi-occluded dermal application of the undiluted test material to intact skin at a dose level of 2000 mg/kg bw. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy at termination of the study.

TEST SITE
- Area of exposure: back and flanks
- % coverage: approximately 10% of the total body surface area
- Type of wrap if used: surgical gauze

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test material
- Time after start of exposure: 24-hour

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.09 mL/kg

Duration of exposure:

24 hours

Doses:

Limit test 2000 mg/kg bw

No. of animals per sex per dose:

1 male and 1 female animal

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity 0.5, 1, 2, 4 hours and one day after dosing.
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: Due to the severity of the dermal reactions noted in the initial two animals, resulting in these animals being killed in extremis one day after dosing, no further animals were treated.

Mortality:

Due to the severity of the dermal reactions, both animals were killed in extremis one day after dosing.

Clinical signs:

other: Signs of dermal irritation noted were brown/green coloured dermal necrosis (attributed a Draize score of 4 for erythema due to injuries in depth), surrounded by a thin margin of blanching and moderate oedema. Well-defined erythema surrounding other dermal

Gross pathology:

No abnormalities detected.

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The animals showed no signs of toxicity but were killed in extremis due to the severity of the dermal reactions. The acute dermal median lethal dose may be considered to be greater than 2000 mg/kg bw although there is insufficient data available to confirm this finding.

Executive summary:

A study was carried out according to EU Method B.3 and OECD Guideline 402 (Acute Dermal Toxicity). The study was performed to assess the dermal toxicity of the test material in the rat. Two animals (one male and one female) were given a single, 24 hour, semi-occluded dermal application of the undiluted test material to intact skin at a dose level of 2000 mg/kg bw. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy at termination of the study.

Due to the severity of the dermal reactions, both animals were killed in extremis one day after dosing. There were no signs of systemic toxicity. Signs of dermal irritation were indicative of dermal corrosion. No abnormalities were noted at necropsy. The acute dermal median lethal dose may be considered to be greater than 2000 mg/kg bw although there is insufficient data available to confirm this finding.