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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:
September 26, 2013 to October 15, 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with OECD test guidelines in compliance with GLP.

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: Clear colorless liquid
Details on test material:
Name: DEGMEE
CAS No.: 1002-67-1
Lot No.: 20130625
Storage condition: Room temperature [(1 ~30)℃]
Expiration date: 2014-06-25
Appearance: Clear colorless liquid
Purity: 99.98 %
Molecular formula and MW: C2H5O(CH2CH2O)2CH3 / 148.20
Specific gravity: 0.918 – 0.928
Water solubility: Soluble

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
Animal species (strain): Crl:CD(SD)-Rat, SPFSupplier: ORIENT BIO Co., Ltd. 699-13, Mokdong-ri, Buk-myeon, Gapyeong-gun, Gyeonggi-do, KoreaNumber of animals and sex distinction at the time of receipt: 11 males, 11 femalesA range of age and body weight at the time of receipt: 7 weeks old, males 205.3 g ~ 220.5 g / females 180.0 g ~ 200.6 gNumber of animals and sex distinction at the time of administration: 10 males / 10 femalesA range of age and body weight at the time of administration: 8 weeks old, males 251.6 g ~ 261.9 g / females 200.8 g ~ 232.1 gTest systemReason for selection of the animal: SD rat is commonly used for various field of toxicology study, and there is a plenty of reference data.Quarantine and acclimation: On receipt the animals were examined for any signs of healthy or injury. The animals were acclimated for 5 days when their health status was assessed.Identification of animals: Identification cards including information such as study number, test substance name, test title, receipt date, quarantine period, allocation date, experimental period, sex, group number and study director's name were indicated. The animals were labeled on tail with permanent marker pen for an individual discrimination.Group allocation: The healthy animals without abnormal sign and with normal body weight gain during the quarantine and acclimation period were selected.Remnant animal: Remnant animals were euthanized after the main study terminated.Animal husbandryEnvironmental conditions: The animal facility was maintained at (22 ± 3) ℃, relative humidity (50 ± 20) %, air ventilation of 10 ∼ 15 times/hr, 12 hours light/dark cycle (light during 8:00 ∼ 20:00) at 150 ~ 300 Lux.Environmental monitoring: The temperature and relative humidity were monitored automatically every half-hour by automatic instrument and other environmental condition (illuminance, ammonia concentration, noise of animal room, etc) measured periodically (1 times/quarter) by SOP of Korea Testing & Research Institute. There were no influenceable variations for study in environmental measurement.Housing: Animals were housed individually in a stainless steel cage [270(W) mm x 500(D) mm x 200(H) mm, Daejong Instrument Industry Co., Ltd., Korea]Feed and water: The animals were fed pellet diet for rat (Cargill Agri Purina, Inc., 56-4, Soryong-dong, Gunsan-si, Jeollabuk-do, Korea) and given the filtered and UV irradiated water ad libitum.Contaminant analysis of feed and water: The feed was considered not to contain any contaminant with periodical analysis results report of manufacturer and the water was periodically analyzed in accordance with SOP of Korea Testing & Research Institute.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
Vehicle: Sterile distilled waterManufactured by: DAI HAN PHARM. CO., LTD.Lot No.: J8LBK21Preparation of test substanceTest substance was suspended at final concentration of 400 mg/mL in sterile distilled water solution. The mixture of the test substance was homogenized by shaking.Administration of test substanceOn the day prior to the patch, the back of each rat was clipped of hairs. The test substance was applied uniformly over an area which was approximately 10 % (4cm × 5cm) of the total body surface area. Test substance were held in contact with the skin with a porous gauze dressing and non-irritating tape(Tegarderm, 3M) throughout a 24-hour exposure period. The wrappings and the adhesive bands were removed at 24 hours after application. The applied sites were washed out gently with distilled water.
Duration of exposure:
24 hours
Doses:
A limit test at one dose level of 2000 mg/kg body weight was carried out.
No. of animals per sex per dose:
5 males and 5 females were used for each group.
Control animals:
yes, concurrent vehicle
Details on study design:
Clinical signs: Clinical signs were carefully observed for 4 hours after treatment and then once everyday for 14 days.Changes of body weight: Body weight was measured at animal receipt day, animal allocation day, just before treatment and on day 7 and 14 after the administration.Necropsy findings: At the end of study period, all animals were sacrificed by bloodletting after ether anesthesia. Neocropsy was conducted for all animals and the organs were examined for gross lesions.
Statistics:
Statistical analyses were performed by comparing the treatment group and the control group using SPSS Statistical Analysis Systems (SPSS Korea Data Solution. Co. Ltd./ ver 19). The data were presented as mean±SD. Variance of numerical data was checked by F-test. Then, the student t test was conducted to determine the significant difference between two groups.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No death occurred in all animals during the experimental period.
Clinical signs:
Clinical signs related with the substance were not observed in any animals during the observation period.
Body weight:
All living animals showed the normal increase of body weight.
Gross pathology:
In all animals, there were no lesions caused by administration of test substance.
Other findings:
No other findings described in the study report.

Any other information on results incl. tables

Tables (Group summary)

 

Mortality

Group

Dose

(mg/kg B.W.)

Mortality (dead / tested)

Male

Female

G1

0

0%

(0 / 5)a

0%

(0 / 5)

G2

2000

0%

(0 / 5)

0%

(0 / 5)

a: Number of dead animals / Number of tested animals

 

Clinical signs

Group

Dose

(mg/kg B.W.)

Sex

Number of animals

Clinical signs

G1

0

Male

5

Normal

Female

5

Normal

G2

2000

Male

5

Normal

Female

5

Normal

 

Body weight                                                      Unit: g

Group

Dose

(mg/kg B.W.)

Sex

 

Days after administration

0

7

14

G1

0

Male

Mean

S.D.

N

256.2

4.2

5

302.3

13.6

5

339.4

26.3

5

Female

Mean

S.D.

N

211.9

12.4

5

227.3

15.5

5

241.5

18.6

5

G2

2000

Male

Mean

S.D.

N

257.1

3.6

5

297.6

10.9

5

330.5

15.1

5

Female

Mean

S.D.

N

211.5

7.3

5

226.0

5.4

5

235.3

7.1

5

N: Number of animals, S.D.: Standard deviation

There were no significant difference between two group; p<0.05

 

Necropsy findings

Findings

Group

(mg/kg B.W.)

G1

(0)

G2

(2000)

Male

Female

Male

Female

Number of examined

5

5

5

5

Gross findings

No gross findings

5

5

5

5

Internal findings

No gross findings

5

5

5

5

 

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
Based on the results, the LD50 value of the DEGMEE was considered to be higher than 2000 mg/kg body weight in rat.
Executive summary:

This study was executed to evaluate acute dermal toxicity of the DEGMEE in SD rats.

This study was executed in accordance with the test regulation: OECD Guideline for Testing of Chemicals, TG 402 “Acute Dermal Toxicity” (February 24, 1987)

 

The present study was conducted to investigate acute dermal toxicity of DEGMEE to the Sprague-Dawley (SD) rats. The test substance was administrated only one time by dermal route at a dose of 2000 mg/kg body weight. After single dose administration, mortality, clinical signs, body weights and necropsy findings were observed for 14 days.

 

- 5 males and 5 females were used in each group, control and 2000 mg/kg body weight group

- No mortality was observed in the present study.

- Clinical signs related with the substance were not observed in any animal during the observation period.

- All tested animals showed normal gains in body weight.

- In all animals, there were no necropsy findings caused by administration of test substance.

 

Based on these results, the LD50 value of the DEGMEE was considered to be higher than 2000 mg/kg body weight in rat.