Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
February 28th - March 14th, 2013
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)
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, April 2011; including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
issued 19 May 2011
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
liquid: viscous
Details on test material:
- Appearance: clear, slightly yellowish to brown, viscous liquid
- Storage condition of test material: at room temperature 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. 10 weeks old)
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean; at start males: 266-285g, females: 185-209g
- 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

IN-LIFE DATES: From: 28 FEB 2013 to 14 MAR 2013

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
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 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 test substance 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 and on test substance data supplied by the sponsor.

Dose volume: 2000 mg/kg (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. No correction was made for purity of the test substance. In order to obtain homogeneity, the test substance (formulations) were heated in a water bath with a maximum temperature of 75ºC for a maximum of 17 minutes. The test substance formulation was allowed to cool down to a temperature of maximally 40ºC prior to dosing.

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: Yes
- Other examinations performed: None
Statistics:
None.

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:
Hunched posture, piloerection and/or chromodacryorrhoea were noted in all males and three females on Days 1 and/or two. Hypothermia was noted in one male on Day 2. No signs of irritation were seen in the treated skin-area of the animals during the observation period.
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:
Two males showed many reddish foci in the thymus and three females showed enlarged size of mandibular lymph nodes during macroscopic post mortem examination. No abnormalities were found in the other animals.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Not classified according to EC Regulation 1272/2008
Conclusions:
In an acute dermal toxicity study with rats, performed according to OECD/EC test guidelines, an LD50 >2000 mg/kg bw was determined.
Executive summary:

An acute dermal toxicity test was conducted with five male and five female rats following OECD and EPA guidelines according to GLP principles. Accelerator (PT 25E or PT 25E/2) was applied occlusively at 2000 mg/kg bw for 24 hours. No mortality occurred. No unexpected changes in body weight gain were reported. Hunched posture, piloerection and/or chromodacryorrhoea were noted in all males and three females on Days 1 and/or two. Hypothermia was noted in one male on Day 2. Two males showed many reddish foci in the thymus and three females showed enlarged size of mandibular lymph nodes during macroscopic post mortem examination. No abnormalities were found in the other animals.

Based on these results, the test substance has an acute LD50 > 2000 mg/kg bw and is not classified for acute dermal toxicity according to EC regulation No 1272/2008.