Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report Date:
2016

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
yes
Remarks:
Animal 1 & 4 w/o bandage at ~1.5hr after dosing. Bandage re-applied. Eval: exposure time ~1.5hr < 24hr; exposure sufficient. Animal 10 w/o bandage day 2; exposure not sufficient. Eval: exposure not sufficient for eval. Sufficient data available for eval.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Batch 605803
- Expiration date of the lot/batch: 23 October 2016
- Purity test date: 25 November, 2015

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature
- Solubility and stability of the test substance in the solvent/vehicle: Soluble at 600 mg/mL in Dimethyl sulfoxide. Stable for 20 hours with 1% mol decrease.


TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test article was homogenized in Dimethyl sulfoxide

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: Young adult animals (approx. 10 weeks old)
- Weight at study initiation: 314 g (males), 192 g (females)
- Fasting period before study: None
- Housing: Individually housed in labeled Makrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey,
United Kingdom).
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: Acclimatization period was at least 5 days before start of treatment under laboratory conditions. During the acclimatization period the animals were group housed in Makrolon cages (MIV type, height 18 cm).
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24°C
- Humidity (%): 40 to 70%,
- Air changes (per hr): At least 10 air changes/hour
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark cycle

IN-LIFE DATES: From: 17 May 2016 To: 02 June 2016

Administration / exposure

Type of coverage:
occlusive
Vehicle:
DMSO
Details on dermal exposure:
TEST SITE
- Area of exposure: Approximately 25 cm² for males and 18 cm² for females on the back of the animal
- % coverage: Approximately 10% of the total body surface
- Type of wrap if used: 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).
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Skin was cleaned of residual test item using tap water.
- Time after start of exposure: 24 hours
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw

VEHICLE
- Amount(s) applied (volume or weight with unit): 4 mL/kg
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration : 14 days
- Frequency of observations and weighing: Day 1 (pre-administration), 8 and 15
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, body weight, gross pathology

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 during the study.
Clinical signs:
Chromodacryorrhoea and/or ptosis were noted for most animals on Day 1. Scabs, focal erythema, general erythema, scales were seen in the treated skin-area of the animals during the observation period. These local effects were considered not to have affected the conclusion of the study.
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
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
Conclusions:
Based on the results of the study, the dermal LD50 in rats was > 2000 mg/kg bw for MTDID 15670.
Executive summary:

MTDID 15670 was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15). No mortality occurred. Chromodacryorrhoea and/or ptosis were noted for most animals on Day 1. The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity. No abnormalities were found at macroscopic post mortem examination of the animals. Based on the results of the study, the dermal LD50 in rats was > 2000 mg/kg bw for MTDID 15670.