Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 29, 2012 - December 13, 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

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:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
(2008)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
(1998)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, April 2011; including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Description: Clear slightly yellow very viscous liquid
- Purity: 100%
- Storage condition of test material: In refrigerator (2-8°C) in the dark

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 Macrolon 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): 18 – 24
- Humidity (%): 40 - 70
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
propylene glycol
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 formulation 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 formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch, 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.

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


No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
VEHICLE
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at WIL Research Europe and on test substance data supplied by the sponsor.

Dose volume: 10 mL/kg body weight

DOSAGE PREPARATION: The formulation (w/w) was prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of the vehicle (1.036) and specific gravity of the test substance (1.220 was used). No correction was
made for purity of the test substance.

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:
Hunched and/or flat posture, chromodarcryorrhoea and piloerection, were noted in the majority of animals on Days 1 and/or 2. One male showed ptosis and one female showed tremor on Days 1 and/or 2.
Body weight:
Five males and three females showed body weight loss in the first week. In the second week these animals recovered and showed body weight gain. The two remaining females showed body weight gain in the first and second week.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Other findings:
General, focal or maculate erythema, necrosis, scabs and scales were seen in the treated skin-area of the animals during the observation period.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute dermal toxicity study with rats, performed according to OECD 402 test guideline and GLP principles, an LD50 >2000 mg/kg bw was determined.
Executive summary:

The test substance was assessed for toxicity in an acute dermal toxicity study with female Wistar rats, performed according to OECD 402 test guideline and GLP principles.

No mortality occurred. Hunched and/or flat posture, chromodarcryorrhoea and piloerection, were noted in the majority of animals on Days 1 and/or 2. One male showed ptosis and one female showed tremor on Days 1 and/or 2. General, focal or maculate erythema, necrosis, scabs and scales were seen in the treated skin-area of the animals during the observation period.

Five males and three females showed body weight loss in the first week. In the second week these animals recovered and showed body weight gain. The two remaining females showed body weight gain in the first and second week.

No abnormalities were found at macroscopic post mortem examination of the animals.

Based on the results the dermal LD50 value of m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline in Wistar rats was

established to exceed 2000 mg/kg body weight.

The test substance, m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.