3,3'-[methylenebis(oxymethylene)]bisheptane

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June 04-21, 2012

Reliability:

1 (reliable without restriction)

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:

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

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3,3'-[methylenebis(oxymethylene)]bisheptane

EC Number:

244-815-1

EC Name:

3,3'-[methylenebis(oxymethylene)]bisheptane

Cas Number:

22174-70-5

Molecular formula:

C17H36O2

IUPAC Name:

3,3'-[methylenebis(oxymethylene)]diheptane

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): 2-ethylhexylal
- Analytical purity: 99.766%
- Impurities (identity and concentrations): 2-Ethylhexanol (0.0826 %), Formaldehyde (not found), Water (0.0370 %)
- Lot/batch No.: 1204051500
- Expiration date of the lot/batch: 3 years / 05.04.2015
- Storage condition of test material: Store in supplied bottle in dark at the temperature under 25°C. Provide local exhaust or general room ventilation. Keep container closed when not in use. Keep away from heat.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Breeding farm VELAZ s.r.o., Koleč u Kladna, Czech Republic, RČH CZ 21760152
- Age at study initiation: not specified
- Weight at study initiation: average of 254.72 kg for males; average of 2175.75 kg for females
- Fasting period before study: not specified
- Housing: animal room with monitored conditions – one animal in one plastic cage
- Diet (e.g. ad libitum): ST 1 BERGMAN – standard pelleted diet ad libitum (producer: Ing.Mrkvička Miroslav - Výroba krmných směsí, Mlýn Kocanda, 252 42 Jesenice u Prahy).
- Water (e.g. ad libitum): drinking tap water ad libitum (quality corresponding to the Regulation No. 252/2004 of Czech Coll. of Law)
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): room temperature 22 + 3 °C, permanently monitored
- Humidity (%): 30 – 70 %, permanently monitored
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12/12

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:

24 hours

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:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:

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.

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.

- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
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.

Statistics:

Not necessary

Results and discussion

Preliminary study:

For male:
no death
30 minutes: no clinical signs of intoxication
3 hours: no clinical signs of intoxication
2nd – 14th day: no clinical signs of intoxication

For female:
no death
30 minutes: no clinical signs of intoxication
3 hours: no clinical signs of intoxication
2nd – 14th day: no clinical signs of intoxication

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was recorded

Clinical signs:

other: No clinical signs of intoxication were detected after application in all animals

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:

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

Executive summary:

Acute dermal toxicity of 2 -ethylhexylal was evaluated in an in vivo test performed according to OECD TG 402 (limit test).

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