Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1990-11-09 - 1991-02-22
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study; well documented study report

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 434 (Acute Dermal Toxicity - Fixed Dose Procedure)
Deviations:
yes
Remarks:
At time of application of substance, the skin of 1/2 the animals t was to be abraded. This was inadvertently not done. All animals on the study had intact skin when dosed. Deviation has not compromise the study.
GLP compliance:
yes
Test type:
other: limited
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
-Source: Charles River Wiga. Sulzfeld, West-Germany
-Age at study initiation: approx. 7 weeks
-Weight at study initiation: males: 253~276 g; females: 167~192 g.
-Fasting period before study: Feed was withheld overnight prior to dosing until approximately 3-4 h after administration of the test article.
-Housing: housed in groups of 5 per sex in polycarbonate cages containing purified sawdust as bedding material.
-Diet: free access to standard pelleted laboratory animal diet (RMH-B from Hope Farms, The Netherlannds)
-Water: free access to tap-water.
-Acclimation period: at least 5 days under laboratory conditions.

ENVIRONMENTAL CONDITIONS
-Temperature (°C): 21± 3 oC
-Humidity (%): 30-70%
-Air changes: 7.5 – 15 air changes per hr
-Photoperiod (12 hrs dark /12 hrs light)

IN-LIFE DATES: From: Jan 5th 1989 To: Jan 19th 1989

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Type of wrap if used: the test material was applied to sleeves of rubber dental dam. Each sleeve will be wrapped around the trunk of the respective animal and secured with staples. An outer layer of gauze was warpped aound the trunck of each animal and secured with tape. Each rabbit was then be fitted with an appropriate restraining device to prevent the removal of the wrapping.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): any unabsorbed test material remaining on the skin was removed by gentle sponging using a tower moistened with water of other solvent.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg (2.05 mL/kg)
- Constant volume or concentration used: no

VEHICLE
- Amount(s) applied (volume or weight with unit): not applicable
- Concentration (if solution): not applicable
- Lot/batch no. (if required): not applicable
Duration of exposure:
24 hours
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5 male, 5 female
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations at peveryday of dosing (day 1) and twice daily thereafter for at least 14 days; Bodyweight measurements taken on days 1 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: body weight, clinical signs, skin irritation, skin fur, eyes and mucous membrane, and behavior pattern, tremors, convulsion, salivations, diarrhea, lethargy, sleep and coma.

Results and discussion

Preliminary study:
not applicable
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
Irritation of skin was noted in all test animals. There were no other clinical signs of toxicity or behavioral changes over the 15 day observation period.
Body weight:
All animals showed expected bodyweight gain during the study.
Gross pathology:
Effects on organs:
No treatment-related macroscopic findings were observed.
Other findings:
- Other observations: The treated skin surface of animals showed irritation.

Any other information on results incl. tables

No deaths were noted during the observation period;

Irritative effects were seen

No clinical changes were observed

All tested animals gained weight and the body weight data is shown below:

Sex

Day 0

Day 15

Male

2993

3230

Female

2906

3207

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) of the test material was found to be greater than 2000 mg/kg bodyweight.
Executive summary:

In an acute dermal toxicity study, a group of New Zealand rabbits (five male and five female) were dermally exposed to the test substance for 24 hours at a dose level of  2000  mg/kg bw.  Animals then were observed for 14 days.

The treated skin surface of animals showed irritation after test material removal, but there were no other clinical signs of toxicity or behavioral changes over the 15 day observation period. Macroscopic examination of all animals at the end of the study did not reveal any changes that were considered to have arisen as a result of treatment.

The dermal LD50 was estimated to exceed 2000 mg/kg bw.