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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 27 November 2012 to 04 February 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD guideline and EU method. GLP study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report date:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
[(±)-(4-amino-2-hydroxy-4-oxobutyl)trimethylammonium] chloride
EC Number:
226-073-0
EC Name:
[(±)-(4-amino-2-hydroxy-4-oxobutyl)trimethylammonium] chloride
Cas Number:
5261-99-4
Molecular formula:
C7H17N2O2.Cl
IUPAC Name:
4-amino-2-hydroxy-N,N,N-trimethyl-4-oxobutan-1-aminium chloride
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Physical state: white powder
- Analytical purity: 99,4%
- Lot/batch No.: WI 2274
- Storage condition of test material: at room temperature not exceeding 40°C.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Germany
- Age at study initiation: 8-week old males; 10-week old females
- Weight at study initiation: males 273-300 g; females 209-241 g
- Housing: The animals were kept in plastic cages with the following dimensions: 58 x 37 x 21 cm (length x width x height). The cages were covered with wire bar lids. After the test item application, the animals were caged individually. After the removal of the test item from the animals’ skin, there were five rats per cage. Each sex was kept separately.
- Diet (e.g. ad libitum): “Murigran” standard granulated laboratory fodder, ad libitum
- Water (e.g. ad libitum): drinking tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 – 22 °C
- Humidity (%): 38 – 67%
- Air changes (per hr): about 16 times/hour
- Photoperiod (hrs dark / hrs light): 12 hours light – 12 hours dark

IN-LIFE DATES: From: 28 November 2012 To: 12 December 2012

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: The area of skin treated with the test item was about 41 cm2 (males) and 31 cm2 (females).
- % coverage: about 10% of the total body skin area.
- Type of wrap if used: The powdered test item was applied to gauze patches. Then, the patches were laid on the prepared skin and covered with PVC foil; an elastic bandage was used to make a circular protecting band.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The band and the gauze patches were taken off and the residual test item was removed using water
- Time after start of exposure: After 24 hours.

Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The evaluation of general condition of the animals, i.e. the observation of all animals for mortality and morbidity was conducted twice a day or once a day (on days off) during the 14-day observation period. The detailed clinical observations were made on the administration day (day 0) at hourly intervals up to 5 hours. From the 1st to the 14th day of the observation period, the detailed clinical observations were performed once a day. The animals’ body weight was determined individually directly before the test item administration (day 0) and then on the 7th and 14th day.
- Necropsy of survivors performed: yes
After the 14-day observation period, all animals were humanely killed by an intraperitoneal administration of morbital at a dose of 200 mg/kg and transferred to the gross examination.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
other: Following a single application of the test item, no general clinical signs were stated in the animals. Pathological changes on the skin in the site of the test item application were not observed.
Gross pathology:
The gross examination did not reveal any pathological changes in the examined animals.

Any other information on results incl. tables

Table 1:    Summary of acute dermal toxicity

Males

Females

Dose

Mortality

Mortality

2000 mg/kg bw

0/5

0/5

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 for the test substance was greater than 2000 mg/kg bw.
Executive summary:

The acute dermal toxicity study, according to the OECD Guideline No. 402 / EU Method B.3, was performed in order to obtain information on health hazards resulting from the possibility of a single exposure due to skin contact with the test item. The test item at a single dose of 2000 mg/kg b.w. was applied to the shaved dorsal skin of 5 males and 5 females for 24 hours. After the administration of the test item, the animals were observed for 14 days. The animals’ body weight was determined individually on day 0 (directly before the administration of the test item) as well as on the 7th and 14th day. After the 14-day observation period, all animals were humanely killed, dissected and subjected to a detailed gross necropsy. Following a single application of the test item, no general clinical signs were stated in the animals.Pathological changes on the animals’ skin in the site of the test item application. All animals survived the period of the experiment were not observed. During the 14-day period of the experiment, all animals’ body weight increased. The gross examination did not reveal any pathological changes in the examined animals. The dermal LD50 for the test substance was greater than 2000 mg/kg bw.