Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
04. 06. – 21. 06. 2012
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2,5,7,10-tetraoxaundecane
EC Number:
224-631-8
EC Name:
2,5,7,10-tetraoxaundecane
Cas Number:
4431-83-8
Molecular formula:
C7H16O4
IUPAC Name:
2,5,7,10-tetraoxaundecane
Test material form:
other: liquid
Details on test material:
Test substance name: 2,5,7,10-TETRAOXAUNDECANE (TOU)
a) information from sponsor
IUPAC name: 2,5,7,10-tetraoxaundecane
Molecular formula: C7H16O4
Molecular weight: 164.20
CAS No.: 4431-83-8
EC No.: 224-631-8
Batch No.: 1204051200
Purity: 99.966 % (w/w)
Impurities: 2-Methoxyethanol (0.0081 % (w/w)); Aldehydes (not found); Water (0.0161 % (w/w))
Storage: Store in supplied bottle in dark at the temperature below 25°C. Provide local exhaust or general room ventilation. Keep container closed when not in use. Keep away from heat.
Stability / Expiration date: 3 years / 05.04.2015
Safety precautions: Do not breathe gas, fumes, vapour and spray. Use respirator and goggles. In case of repeated or prolonged contact wear gloves.
b) information from test facility
Appearance: colourless liquid
pH: Approximately 6 (by contact of application form with universal indicator pH strip moistened with water, strip
producer Lach-Ner, s.r.o. Neratovice)
Storage: During the study the test substance was stored in well closed original bottle in dark at the laboratory temperature.

Test animals

Species:
rat
Strain:
other: Wistar Han
Sex:
male/female
Details on test animals or test system and environmental conditions:
Species: Laboratory rat
Strain: Wistar Han, monitored quality (quality status guaranteed by supplier)
Source: Breeding farm VELAZ s.r.o., Koleč u Kladna, Czech Republic, RČH CZ 21760152
Sex: Males and females
Acclimatisation: 5 days
Total number: 5 males + 5 females
Housing: animal room with monitored conditions – one animal in one plastic cage
Diet: ST 1 BERGMAN – standard pelleted diet ad libitum (producer: Ing.Mrkvička Miroslav - Výroba krmných směsí, Mlýn Kocanda, 252 42 Jesenice u Prahy).
Water: drinking tap water ad libitum (quality corresponding to the Regulation No. 252/2004 of Czech Coll. of Law)
Microclimatic conditions: room temperature 22 + 3 °C, permanently monitored relative humidity 30 – 70 %, permanently monitored light: 12 hour light/12 hour dark
Bedding: sterilized shavings of soft wood
Identification of animals: colour marks on tail, each cage was marked with the number of study, number of animal, sex, name and dose of the test
substance.
Randomisation: according to the internal rule, at the start of the study the weight variation of animals was minimal and did not exceed + 20 % of the mean weight for each sex.
Health condition: certificate of good health condition – from breeding farm; no signs of diseases were observed at clinical check-in, during
the acclimatisation period and before the start of study.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Preparation of experimental animals
Approximately 24 hours before application, a skin area of about 6 x 6 cm on the back of animals was shaved (aprox. 10% of the body surface). The animals were weighed immediately before application.

Preparation and application of the test substance
The amount of test substance for each animal was weighed out (according to its body weight and the dose) immediately before application.
The test substance in delivered form was applied on the depilated area of skin. The application site was covered by mull and held in contact by plaster (strapping). After 24 hours the semiocclusive dressing was removed, and remains of the test substance were wiped off with water.
Duration of exposure:
14 days
Doses:
The study was performed as limit test: two groups of animals – 5 males and 5 females and the dose of 2000 mg/kg. The pre-test was performed with 1 male and 1 female of the groups of the five animals. The pre-test was started one day before the start of limit test.
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
Time schedule of observations
Body weight: before application, 8th and 15th day of study
Mortality: daily
Clinical signs: daily
Pathological examination: 15th day of study

Body weight recording
The animals were weighed at the start of the study (before application), at 8th day and at the end of experiment (15th day). The average body weight of the groups was calculated from individual body weights.
Body weight increments were calculated from the body weight at the start of the study, during the first week and at the end of the study (see table No. 1 and No. 2).

Clinical observation
After application the animals were observed individually – at the first day: twice (30 minutes and 3 hours after application), at the second day: twice (in the morning and in the afternoon) and daily thereafter for 14 days.
Observations included changes in skin and fur, eyes, visible mucous membranes, nutritive condition, autonomic and central nervous systems, psychic activity, somatomotor activity, reactions to stimuli, function of respiratory, circulatory, digestive and urogenital system.
Also presence of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma was carefully observed.

Pathological examination
All test animals survived to the end of study were sacrificed on the 15th day by injection of veterinary preparation T61 (1 ml iv.) and gross necropsy was carried out. Nutritious status, body surface, body foramina, thoracic, abdominal and cranial cavity were evaluated. All gross macroscopic changes of organs and tissues were recorded on special data sheets.

Results and discussion

Preliminary study:
not relevant
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No death was detected after application in all animals.
Clinical signs:
No clinical signs of intoxication were detected after application in all animals.
Body weight:
In males and females, the weight increments were adequate to species and age of animals in the experiment with average weights of:
- 260.67 g before application, 286.97 g at day 8 and 327.19 g at day 15 for males
- 222.52 g before application, 229.53 g at day 8 and 242.95 g at day 15 for females
Gross pathology:
No macroscopic changes were diagnosed during pathological examination in all animals
Other findings:
None

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Evaluation of results
The test substance toxicity was evaluated on the basis of mortality, body weight changes, and clinical signs of toxicity during the observation period and necropsy findings at the end of study.
The test substance applied on skin at a dose of 2000 mg/kg of animal weight did not cause death of animals.
No clinical signs of intoxication were observed. No macroscopic changes were diagnosed during pathological examination of animals.

Test substance toxicity characterization
According to the results of study, the value of LD50 (dermal) of the test substance, 2,5,7,10-TETRAOXAUNDECANE (TOU), is higher than 2000 mg/kg of body weight for rats of both sexes.
Executive summary:

The test substance, 2,5,7,10-TETRAOXAUNDECANE (TOU), was tested for acute dermal toxicity using Wistar rats. Testing was performed according to the Method B.3 Acute Toxicity (Dermal), Council Regulation (EC) No.440/2008, published in O.J. L 142, 2008.

The study was performed as limit test: two groups of animals – 5 males and 5 females at the dose of 2000 mg/kg of body weight. The pre-test was performed with 1 male and 1 female from each group. After end exposure test substance of these pilot animals, the other animals of the group were dosed. The test substance was applied on the shaved skin of the test animals in delivered form for 24 hours. The test animals were observed 14 days after exposure test substance, afterwards they were sacrificed, and the necropsy for macroscopic examination of the organs was performed.

The test substance applied at the dose of 2000 mg/kg of body weight did not cause death of animals. No clinical signs of intoxication were observed. No macroscopic change was diagnosed during pathological examination of animals.

According to the results of study, the value of LD50 (dermal) of the test substance, 2,5,7,10-TETRAOXAUNDECANE (TOU), is higher than 2000 mg/kg of body weight for rats of both sexes.

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