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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 May 2012 - 20 June 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed according to OECD guideline and GLP.

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld
- Age at study initiation: Young adult rats
- Weight at study initiation: Between 200 g and 265 g
- Fasting period before study: NA
- Housing: Standard housing conditions
Housing: Individual caging
Cage type: Type II. polypropylene/polycarbonate
Bedding: Laboratory bedding:
Lignocel Hygienic Animal Bedding produced by J. Rettenmaier & Söhne GmbH+Co.KG (Holzmühle 1, 73494 Rosenberg, Germany); A copy of the relevant Certificate of Analysis is maintained in CiToxLAB Hungary Ltd.'s archive.
- Diet (e.g. ad libitum): Animals received ssniff® “Autoclavable complete diet for rats and mice – breeding and maintenance” produced by ssniff Spezialdiäten GmbH, D-59494 Soest, Germany ad libitum, and tap water from the municipal supply, as for human consumption from 500 ml bottle ad libitum. The food is not considered to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
The batch of feed employed in the study was:
• 719 6627, expiry date: May 2012
• 601 7197, expiry date: September 2012
The supplier provided an analytical certificate for the batch used. Copy of the certificates will be archived with the raw data.
- Water (e.g. ad libitum):
Water quality control analysis is performed once every three months and microbiological assessment is performed monthly, by Veszprém County Institute of State Public Health and Medical Officer Service (ÁNTSZ, H-8201 Veszprém, József A.u.36., Hungary). The quality control results are retained in the archives at CiToxLAB Hungary Ltd.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.9-24.9
- Humidity (%): 38-61
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 16 May 2012 - 20 June 2012

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back
- % coverage: 10
- Type of wrap if used: The back of each animal was shaved (approximately 10 % area of the total body surface) approximately 24 hours prior to treatment. The test item was applied as a single dose as supplied to the shaved skin and remained in contact with the skin for the 24- hour exposure period. Sterile gauze pads were placed on the skin of rats to cover the test item. These gauze pads were kept in contact with the skin by a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was then wrapped with semi occlusive plastic wrap for 24 hours.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the exposure period, the area of skin treated with the test item was washed with lukewarm water.
- Time after start of exposure: 24 hours.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 or 1000 mg/kg bw
- Constant volume or concentration used: No, based on bodyweight
Duration of exposure:
24 hours
Doses:
2000 or 1000 mg/kg bw
No. of animals per sex per dose:
2000 mg/kg bw: 5
1000 mg/kg bw: 5 females
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical observations were performed on the day of treatment at 1 and 5 hours after application of the test item and once each day for 14 days thereafter. Observations included the skin and fur, eyes and mucous membranes, the respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation,
diarrhoea, lethargy, sleep and coma.
The body weights were recorded on Day 0 (before test item administration) and on Days 7 and 14.
- Necropsy of survivors performed: yes, m acroscopic examination was performed on all animals. All surviving animals were
anaesthetised with Euthasol®40% and exsanguinated. After examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs was observed. All macroscopic changes were recorded.
Statistics:
None

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
> 1 000 - < 2 000 mg/kg bw
Based on:
test mat.
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Administration of the test item at a dose level of 2000 mg/kg bw caused mortality (4 of 5 females). The animals were found dead on observation day 1. No mortality in males was observed.
Treatment at a dose level of 1000 mg/kg bw did not cause mortality in females.
Clinical signs:
Treatment at a dose level of 2000 mg/kg bw caused decreased activity, hunched back position and piloerection. Treatment at a dose level of 1000 mg/kg bw did not cause any test item related clinical signs. No treatment related local dermal signs were observed at a dose level of 2000 mg/kg bw and at a dose level of 1000 mg/kg bw.
Body weight:
The body weight and body weight gain of animals did not show any test item-related effect.
Gross pathology:
There was no evidence of test item-related macroscopic observations in surviving animals at a dose level of 2000 mg/kg bw and at a dose level of 1000 mg/kg bw. Dark/red discolouration of the non-collapsed lungs was observed in females found dead, which is considered to be typical for animals found dead.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The acute dermal median lethal dose (LD50) of the test item Bis-(2- chloroethoxy)methane was found to be higher than 2000 mg/kg body weight in male and between 1000 mg/kg body weight and 2000 mg/ kg body weight in female CRL:(WI) rats.
Executive summary:

An acute dermal toxicity study was performed with test item Bis-(2 - chloroethoxy)methane in CRL:(WI) rats, in compliance with OECD Guideline No.: 402. A limit test was carried out at 2000 mg/kg body weight (bw) in both sexes (5 rats/sex) and an additional dose group (5 females) was treated at the dose level of 1000 mg/kg bw. The test item was applied as supplied as a single dermal 24-hour exposure followed by a 14-day observation period.

Clinical observations were performed on all animals at 1 and 5 hours after dosing and daily for 14 days thereafter. Body weight was measured prior to dosing on Day 0 and on Days 7 and 14. Gross macroscopic examination was performed on all surviving animals at the end of the 2-week observation period (Day 14).

The results of the study were summarized as follows:

Mortality

Administration of the test item at a dose level of 2000 mg/kg bw caused mortality (4 of 5 females). The animals were found dead on observation day 1. No mortality in males was observed. Treatment at a dose level of 1000 mg/kg bw did not cause mortality in females.

Systemic clinical signs

Treatment at a dose level of 2000 mg/kg bw caused decreased activity, hunched back position and piloerection. Treatment at a dose level of 1000 mg/kg bw did not cause any test item related clinical signs.

Local dermal signs

No treatment related local dermal signs were observed at a dose level of 2000 mg/kg bw and at a dose level of 1000 mg/kg bw.

Body weight

The body weight and body weight gain of surviving animals did not show any test item-related effect.

Necropsy

There was no evidence of test item-related macroscopic observations in surviving animals at a dose level of 2000 mg/kg bw and at a dose level of 1000 mg/kg bw. Dark/red discolouration of the non-collapsed lungs was observed in females found dead, which is considered to be typical for animals that are found dead.

Conclusions

The acute dermal median lethal dose (LD50) of the test item Bis-(2- chloroethoxy)methane was found to be higher than 2000 mg/kg body weight in

male and between 1000 mg/kg body weight and 2000 mg/ kg body weight in female CRL:(WI) rats.