Trimethyl-3-[(1-oxo-10-undecenyl)amino]propylammonium methyl sulphate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

16 May 2012 and 30 May 2012.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Recently conducted guideline study to GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Methyl trimethyl-3-[(1-oxododecyl)amino]propylammonium sulphate

EC Number:

234-204-8

EC Name:

Methyl trimethyl-3-[(1-oxododecyl)amino]propylammonium sulphate

Cas Number:

10595-49-0

IUPAC Name:

3-(dodecanoylamino)-N,N,N-trimethylpropan-1-aminium methyl sulfate

Test material form:

liquid: viscous

Details on test material:

Sponsor's identification : RL 590/11
Description : pale yellow liquid
Batch number : 1023J29202
Purity : 39.7%
Date received : 30 March 2012
Expiry date : 31 December 2012
Storage conditions : room temperature in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Number: Five male and five female
- Source: Harlan Laboratories UK Ltd., Oxon, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: at least 200g. The weight variation did not exceed ±20% of the mean weight for each sex.
- Housing: suspended solid-floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-Hour exposure period and in groups of five, by sex, for the remainder of the study.
- Diet and Water: Free access to mains drinking water and food (2014C Teklad Global Rodent diet) 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.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30-70%
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (06:00 to 18:00) and twelve hours darkness

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

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

REMOVAL OF TEST SUBSTANCE
- Washing (if done): bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water
- Time after start of exposure: 24 hour

Duration of exposure:

24 hours

Doses:

- Dose level: 2000 mg/kg bodyweight
- Dose Volume: 1.97 ml/kg (based on specific gravity of the test substance of 1.016)

No. of animals per sex per dose:

5 male, 5 female

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: ½, 1, 2 and 4 hours after dosing and subsequently once daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test item was made.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: There were no signs of systemic toxicity.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

Signs of dermal irritation noted were very slight to well-defined erythema, very slight to slight oedema, haemorrhage of dermal capillaries, blanching of the skin, light brown discolouration of the epidermis, loss of skin elasticity, crust formation, small superficial scattered scabs, scab lifting at edges to reveal dried blood and scab lifting to reveal glossy skin.

Any other information on results incl. tables

Dermal Reactions

Animal	Erythema	Oedema
1-0 Male	2 - reversible by day 7	2 - reversible by day 5
1-1 Male	2 - reversible by day 10	1 - reversible by day 6
1-2 Male	2 - reversible by day 8	1 - reversible by day 5
1-3 Male	2 - reversible by day 11	1 - reversible by day 6
1-4 Male	2 - reversible by day 9	2 - reversible by day 6
2-0 Female	2 - reversible by day 9	2 - reversible by day 9
2-1 Female	2 - reversible by day 7	2 - reversible by day 5
2-2 Female	2 - reversible by day 10	2 - reversible by day 5
2-3 Female	2 - reversible by day 10	2 - reversible by day 7
2-4 Female	2 - reversible by day 7	1 - reversible by day 5

Erythema

2 - Well-defined erythema

Oedema

2 - Slight oedema (edges of area well-defined by definite raising)

1 - Very slight oedema (barely perceptible)

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal LD50 was >2000 mg/kg bodyweight.

Executive summary:

The acute dermal toxicity of CAS#10595 -49 -0 was assessed in the Wistar strain rat. The method was designed to be compatible with OECD 402 and Method B3 Acute Toxicity (Dermal) of EC No. 440/2008.

A group of ten animals (five males and five females) was given a single, 24 hour, semi-occluded dermal application of the undiluted test item to intact skin at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

There were no deaths. There were no signs of systemic toxicity. Signs of dermal irritation noted were very slight to well-defined erythema, very slight to slight oedema, haemorrhage of dermal capillaries, blanching of the skin, light brown discolouration of the epidermis, loss of skin elasticity, crust formation, small superficial scattered scabs and scab lifting to reveal dried blood or glossy skin.

Animals showed expected gains in bodyweight, except for one female which showed bodyweight loss during the first week but expected gain in bodyweight during the second week. No abnormalities were noted at necropsy.

The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.