Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
27 October 2011 - 10 November 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.

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:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000; including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

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

Test animals

Species:
rat
Strain:
other: Wistar strain, Crl:WI (Han)
Sex:
male/female
Details on test animals and environmental conditions:
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 11 weeks old)
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean.
- Housing: Individually housed in labeled Makrolon cages
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.3 – 20.9ºC
- Humidity (%): 45 - 64%
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 27 October 2011 - 10 November 2011

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.

The test substance was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The test substance 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.
*. Manufacturers: Laboratoires Stella s.a., Liege, Belgium (surgical gauze) and 3M, St. Paul, Minnesota, U.S.A. (Coban & Micropore).

Frequency: Single dosage, on Day 1.

Washing: Following application, dressings were removed and the skin cleaned of residual test substance using tap water.
Duration of exposure:
24 hours.
Doses:
2000 mg/kg
(1.667 mL/kg)

No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Dose volume: 1.667 mL/kg

DOSAGE PREPARATION: The test substance was dosed undiluted as delivered by the sponsor.

Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
- Other examinations performed: none.
Statistics:
None.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Chromodacryorrhoea (three males and two females), lethargy and ptosis (one male and one female), and piloerection (two males and three females) were observed on Day 1 only (at 2 and/or 4 hours after start of application).

Yellow staining of the treated skin area was shown by three males between Days 6 and 15 and one female between Days 6 and 12. Scales on the treated skin area were shown by two males and two females on Day 5, one male between Days 7 and 12, one male between Days 5 and 7, and one female between Days 5 and 14. One male showed scabs on the treated skin area on Days 5 and 6.
Body weight:
One animal (no. 1) did not show weight gain between Days 1 and 8. All other animals either showed slight weight gain (nos. 6, 8 and 9) or slight weight loss (1-5% for nos. 2-5, 7 and 10) between Days 1 and 8. All animals recovered during the second week of observation.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 value of bis(2,3-epoxypropyl) cyclohexane-1,2-dicarboxylate in Wistar rats was established to exceed 2000 mg/kg body weight.

Based on these results, bis(2,3-epoxypropyl) cyclohexane-1,2-dicarboxylate does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to the:
- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2007),
- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.
Executive summary:

Male and female rats (WISTAR) were treated dermally by occlusive application during 4 hours at a dosage of 2000 mg/kg body weight. The test item was applied undiluted. The animals were observed for clinical signs at periodic interval on the day of dosing and once daily after until day 15 and for mortality/viability twice daily. The animals were weighed on day 1 (prior to the application) and on days 8 and 15.

No deaths occurred during the course of the study. Chromodacryorrhoea (three males and two females), lethargy and ptosis (one male and one female), and piloerection (two males and three females) were observed on Day 1 only (at 2 and/or 4 hours after start of application).

No abnormal body weight changes were noted.

At necropsy, no changes were noted.

The acute dermal median lethal dose (LD50) of bis(2,3-epoxypropyl) cyclohexane-1,2-dicarboxylate in rats is greather than 2000 mg/kg body weight.