Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 15th November 2011 to 8th May 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

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
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: Clear colourless to slightly yellowish viscous liquid
- Analytical purity: UVCB
- Storage condition of test material: At room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 11 weeks old) were selected.
- Weight at study initiation: Males: 301-321 g; Females: 196-217 g
- Housing: Individually housed in labeled Makrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) 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: at least 5 days before start of treatment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 ± 3.0ºC (actual range: 19.9 – 21.7ºC)
- Humidity (%): 40-70% (actual range: 44 - 53%)
- Air changes (per hr): approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day.

IN-LIFE DATES: From: 08 December 2011 To: 22 December 2011

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: approx. 25 cm² for males and 18 cm² for females.
- % coverage: approx. 10% of the total body surface
- Type of wrap if used: The test substance 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.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 hours, after which dressings were removed and the skin cleaned of residual test substance using tap water.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg (1.845 mL/kg) body weight.

Duration of exposure:
24 hours
Doses:
2000 mg/kg (1.845 mL/kg) body weight.
No. of animals per sex per dose:
Five animals per sex per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 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. The time of onset, degree and duration were
recorded and the symptoms graded according to fixed scales:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
- Necropsy of survivors performed: yes. 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.

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:
Piloerection and/or chromodacryorrhoea were noted in two males and four females on Days 1 and/or 2.
Scales and scabs were seen in the treated skin-area of one male and one female between Days 4 and 15.
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:
Several reddish foci were noted in the lungs of one male. No further abnormalities were found at macroscopic post mortem examination of the other animals.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 value of the test substance in Wistar rats was established to exceed 2000 mg/kg body weight.
Executive summary:

The test substance 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. Piloerection and/or chromodacryorrhoea were noted in two males and four females on Days 1 and/or 2. Scales and scabs were seen in the treated skin-area of one male and one female between Days 4

and 15. 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. Several reddish foci were noted in the lungs of one male. No further abnormalities were found at macroscopic post mortem examination of the other animals. The dermal LD50 value of the test substance in Wistar rats was established to exceed 2000 mg/kg body weight.