Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 September 2017 - 10 October 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
August 1998
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
May 2008
Deviations:
no
Qualifier:
according to
Guideline:
other: Appendix to Director General Notification, No. 12-Nousan-8147. Agricultural Production Bureau, Ministry of Agriculture, Forestry and Fisheries of Japan (JMAFF)
Version / remarks:
November 2000, including the most recent revisions
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
dd. 03 November 2015
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
Appearance: white to off white powder or flakes
Storage conditions: at room temperature protected from light
Specific details on test material used for the study:
Stability in vehicle: Stability for at least 5 hours at room temperature under normal laboratory conditions and 8 days in the refrigerator is confirmed over the concentration range 1 to 200 mg/mL

Test animals

Species:
rat
Strain:
other: Crl: WI(Han)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females nulliparous and non-pregnant:yes
- Age at study initiation: approx. 10 weeks old
- Weight at study initiation: males: 270-296 g; females: 182-189 g.
- Fasting period before study: no
- Housing: Group housing (up to 5 animals of the same sex together) on arrival and individual housing during the study. Polycarbonate cages (Makrolon MIV type; height 18 cm.) containing sterilized sawdust were used.
- Diet: Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany), ad libitum throughout the study, except during designated procedures.
- Water: Municipal tap-water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Humidity (%): 45-67
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 26 September 2017 To: 10 October 2017

Administration / exposure

Type of coverage:
occlusive
Vehicle:
polyethylene glycol
Remarks:
(PEG400; specific gravity: 1.125)
Details on dermal exposure:
TEST SITE
- Area of exposure: 25 cm^2 for males, 18 cm^2 for females
- % coverage: 10% of the total body surface
- Type of wrap if used: The test item was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): using the vehicle
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: 2000 mg/kg bodyweight
- Constant volume or concentration used: yes
Duration of exposure:
24 hours
Doses:
2000 mg/kg bodyweight (10 mL/kg bodyweight)
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Mortality: twice daily; Clinical observations: at periodic intervals on the day of dosing (at least three times) and once daily thereafter; Body weights: on day 1 (pre-administration), day 8 and day 15.
- Necropsy of survivors performed: yes

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 mortality occurred.
Clinical signs:
Chromodacrorrhoea (snout) was noted for one male on Day 2.
Scabs (right flank or left flank) or general erythema (back and left flank) were noted for four females during the observation period. These local effects were considered not to have affected the conclusion of the study.
Body weight:
Overall body weight gain in males and females was within the range expected for rats of this strain and age used in this type of study and were therefore considered not indicative of toxicity.
The incidence of slight body weight loss or reduced body weight gain on between Days 8 and 15 in two females were considered not indicative of toxicity, based on the absence of any corroborative findings in these animals.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Not classified according to Regulation (EC) No. 1272/2008.
Conclusions:
The dermal LD50 value of Ethylene glycol dibenzoate in Wistar rats was established to exceed 2000 mg/kg body weight. Based on this result, the test item is not classified according to GHS and Regulation (EC) No. 1272/2008.
Executive summary:

The dermal LD50 value of Ethylene glycol dibenzoate in Wistar rats was established to exceed 2000 mg/kg body weight. Based on this result, the test item is not classified according to GHS and Regulation (EC) No. 1272/2008.