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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
06SEP2012 to 20SEP2012
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, November 2000; 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:
solid: crystalline
Details on test material:
- Physical appearance: yellow crystals
- Storage conditions: 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. 12 weeks old)
- Weight at study initiation: 319g -362g for males, 198g - 236g for females
- Housing: Group housing (acclimatization period) or individual housing (experimental period) 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.
- Acclimatization 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 06SEP2012 to 20SEP2012

Administration / exposure

Type of coverage:
occlusive
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 elastic bandage. A piece of 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: water
- 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: 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.

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: The animals surviving to the end of the observation period were sacrificed by oxygen/carbon dioxide procedure. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities recorded.
Statistics:
None performed.

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:
One female was found dead on day 2 of treatment.
Clinical signs:
Chromodacryorrhoea and/or piloerection were noted in the majority of animals between days 1 and 3. Hunched posture was seen in one male on Day 1 and flat posture was seen in one male on day 1.
The animal found dead showed hunched posture, piloerection, chromodacryorrhoea and ptosis on day 1.
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:
Macroscopic post mortem examination of the animal that died during the study and of the animals surviving to the end of the study did not reveal any abnormalities.
Pelvic dilation of the kidneys (one male), is commonly noted among rats of this age and strain and were therefore considered not toxicologically significant.
Other findings:
Scales were seen in the treated skin-area of one animal during the observation period.

Applicant's summary and conclusion

Interpretation of results:
other: Not classified according to Regulation (EC) 1272/2008
Conclusions:
In an acute dermal toxicity study with rats, performed according to OECD/EC test guideline, an LD50 >2000 mg/kg bw was determined.
Executive summary:

An acute dermal toxicity test was performed according to OECD/EC guideline and GLP principles. Five male and five female rats were exposed to 2000 mg/kg bw for 24 hours. One female was found dead on day 2, this animal showed hunched posture, piloerection, chromodacryorrhoea and ptosis on day 1. In the majority of the other rats, clinical signs such as chromodacryorrhoea and/or piloerection were noted between days 1 and 3. Hunched posture was seen in one male on day 1 and flat posture was seen in one male on day 1. No changes in body weight gain were noted, no abnormalities were found after nacroscopical examination. Scales were seen in the treated skin-area of one animal during the observation period.

Based on these data, the test substance is not classified for acute dermal toxicity.