Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24th August 2005 to 7th September 2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviation from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Protocol deviation: No body weight determined of the male found dead on Day 2. the study data not adversely affected by this deviation.
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: JMAFF Guidelines (2000), including the most recent revisions
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Identification: EA-3098
Description: White powder
Batch: P-32681
Purity: not indicated by the sponsor; treated as 100% pure
Storage: room temperature in the dark
Stability under storage conditions: Stable
Expiry date: 6th June 2009

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: Approximately 8 weeks
- Weight at study initiation: Males: 255 - 281 g, Females: 183-193 g. Body weight variation did not exceed +/-20% of the sex mean.
- Fasting period before study: None.
- Housing: Individually housed in labeled Macrolon cages (MIII type, height 18 cm), containing sterilized sawdust as bedding material and paper as cage-enrichment.
- Diet: Ad libitum access to standrd pelleted laboratory animal diet (from Altromin (code VRF 1), Lage, Germany).
- Water: ad libitum access to tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): actual range of 20.5 - 22.5°C
- Humidity (%): actual range of 41 - 85%
- Air changes (per hr): approximately 15 per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
propylene glycol
Details on dermal exposure:
TEST SUBSTANCE PREPARATION
Vehicle: Propylene glycol
Rationale: The vehicle was selected based on trial formulations performed and on test substance data supplied by the data.
Preparation: The formulation (w/w/) was prepared within 4 hours prior to dosing. Homogeneity was accopmplished to a visually acceptable level. Adjustment was made for specific gravity of the vehicle.


TEST SITE
- Clipping: One day before exposure an anrea of approximately 5 x 7 cm on the back of the animal was clipped.
- Area of exposure: back, 25 cmsquared for males and 18 cm quared for females
- % coverage: The formulation was applied in an area of approx. 10% of the total body surface
- Type of wrap if used: The formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch (surgy 1D), succesively covered with aluminium 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
- Washing (if done): Sfter 24 hours dressings were removed and the skin cleaned of residual test substance removed using tap water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Dose volume - 10 ml/kg bodyweight
- Concentration (if solution): Dose level - 2000 mg/kg body weight
- Constant volume or concentration used: yes

Duration of exposure:
Single dose with 24 hour contact period.
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males and 5 females at 2000 mg/kg.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Observations were made for mortality/viability twice daily. Bodyweights were recorded on Day 1 (pre-administration), Day 8 and Day 15.

- 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.

- Other examinations performed:
Clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded.
Statistics:
No statistical analysis performed.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 1
One male was found dead on day 2 of treatment.
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
Flat or hunched posture, ptosis and/or chromodacryorrhoea were noted in all males and some females on day 1 and/or 2.
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 test substance related abnormalities were found at macroscopic post mortem examination of the animals.
In one male diaphragmatic hernia of the liver was observed, which is an incidental finding occasionally noted among rats of this age and strain. This was therefore considered not toxicologically significant.
Other findings:
Scales and/or scabs were seen in the treated skin-area of all females and one male during the observation period.

Any other information on results incl. tables

The dermal LD50 value of EA-3098 in Wistar rats was established to exceed 2000 mg/kg body weight.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 value of EA-3098 in Wistar rats was established to exceed 2000 mg/kg body weight
Executive summary:

Assessment of the acute dermal toxicity of EA-3098 in the rat was determined according to the following methods:

-OECD No. 402 (1987) "Acute Dermal Toxicity"

-EC Council directive 67/548/EEC, Annex V, B.3 (1992) "Acute Toxicity (Dermal)2

-EPA OPPTS. 870.1200 (1998), "Acute Dermal Toxicity"

-JMAFF Guidelines (2000), including the most recent revisions.

EA-3098 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).

One male was found dead on Day 2 of treatment.

Flat or hunched posture, ptosis and/or chromodacryorrhoea were noted in all males and some females on Day 1 and/or Day 2.

Scales and/or scabs were seen in the treated skin-area of all females and one male during the observation period.

The body weight gain of the surviving animals during the observation period was within the range expected for rats used in this type of study.

No test substance related abnormalities were found at macroscopic post mortem examination of the animals.

The dermal LD50 value of EA-3098 in Wistar rats was established to exceed 2000 mg/kg body weight.