Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
04DEC2012 - 18DEC2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.

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
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): Oxooil LS13
- Substance type: organic
- Physical state: Clear colourless liquid
- Expiration date of the lot/batch: 11 October 2013 (allocated by WIL Research Europe B.V., 1 year after receipt of the test substance)
- Storage condition of test material: In refrigerator (2-8°C) in the dark under nitrogen
- Hygroscopic: Yes, store in well-sealed container
- Volatile: Yes, vapour pressure: 500 Pa at 20°C
- Reactivity: Reactive to oxygen
- Specific Gravity / Density: 0.77 – 0.8

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: 265g - 296g for males; 181g - 215g for females
- Housing: Group housed (acclimatization period) and individually housed (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 04DEC2012 - 18DEC2012

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
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 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 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:
Dose volume: 2000 mg/kg (2.53 mL/kg) body weight. Dose volume calculated as dose level (g/kg) / specific gravity (0.79).

DOSAGE PREPARATION: The test substance was dosed undiluted as delivered by the sponsor. 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 levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Limit test: concentration tested = 2000 mg/kg
Sex:
male/female
Dose descriptor:
other: LOAEL
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Signs of systemic toxicity and skin effects noted in animals treated at a dose level of 2000 mg/kg
Mortality:
No mortality occurred.
Clinical signs:
Lethargy, hunched posture, piloerection, chromodacryorrhoea, shallow respiration and/or ptosis were noted among all animals between Days 1 and 4.
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:
Reddish discoloration of the thymus was noted for one female. No further macroscopic abnormalities were noted.
Other findings:
General/maculate/focal erythema, scales and/or scabs were noted on the treated skin area of all animals during the observation period. For one female, hyperthermia of the treated skin area was noted on Day 3.

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/EC test guidelines, an LD50 >2000 mg/kg bw was determined.
Executive summary:

An acute dermal toxicity study was, performed according to OECD/EC test guidelines and GLP principles. Five male and five female rats were exposed to 2000 mg/kg bw for 24 hours. No mortality occurred or deviations from normal body weight gain. In the first four days after exposure, clinical signs such as lethargy, hunched posture, piloerection, chromodacryorrhoea, shallow respiration and/or ptosis were noted among all animals. General/maculate/focal erythema, scales and/or scabs were noted on the treated skin area of all animals during the observation period. For one female, hyperthermia of the treated skin area was noted on Day 3.

No macroscopic abnormalities were noted, apart from reddish discoloration of the thymus in one female. Based on these data, the acute dermal toxicity of Oxooil LS13 was found to be greater than 2000 mg/kg bodyweight (Globally Harmonised Classification System - not classified).