Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
6 September 1983 - 11 October 1093
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 434 (Acute Dermal Toxicity - Fixed Dose Procedure)
GLP compliance:
not specified
Test type:
fixed dose procedure

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature

OTHER SPECIFICS:
SPECIFIC GRAVITY: 0.874 (SUPPLIED BY SPONSOR)

Test animals

Species:
rat
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazleton Dutchland Inc., PA
- Age at study initiation: Approx 16 weeks
- Weight at study initiation: 2.46 to 3,04 Kg
- Housing: Individual suspended stainless steel cage
- Diet: Purina rabbit chow HF (pellets)(ad libitum)
- Water: Automatic watering system (ad libitum)
- Acclimation period: Approx 36 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22 °C
- Humidity (%): 40-70
- Photoperiod (hrs dark / hrs light): 12 hours light/dark

IN-LIFE DATES: FROM: OCTOBER 11, 1983 TO: OCTOBER 25, 1983

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: The dorsal surface from the shoulder region to the lumbar region
- Type of wrap if used: Gauze patch was secured to the trunk of the animal with tape and a plastic sleeve

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test substance was removed, where possible, using water without altering existing response or the integrity of the epidermis

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 3,160 mg/kg
Duration of exposure:
24 hours
Doses:
3160 mg/kg
No. of animals per sex per dose:
3 males/females
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Clinical observations were made for the nature, onset, and duration of toxicological signs 2 and 4 hours after dosing and once per day thereafter, for a total of 14 days. Body weights were recorded on the day of dosing (day 0), on day 7 and day 14

- Necropsy of survivors performed: yes. After the day 14 weighings and observations, all rabbits were euthanized intravenous administration of sodium pentobarbital. Postmortem gross examinations were performed on all animals by qualified personnel.
Statistics:
The means and standard deviations of the body weights were calculated

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3 160 mg/kg bw
Mortality:
All animals survived until termination of the study.
Clinical signs:
Erythema, ranging from very slight to severe, was noted in all animals at 24 hours and on day 3. By day 7, very slight to well-defined erythema was observed in 5 animals and persisted in 4 animals at study termination. Very slight edema was noted in 4 animals at 24 hours. At day 7, the edema scores of 3 animals increased to slight (edges of area well-defined by definite raising). By study termination, 2 animals continued to show signs of very slight edema. Two animals exhibited eschar at the 24 hour and day 3 dermal evaluations. Desquamation was observed in all animals on day 7 and in 4 animals at termination.

During clinical in-life observations decreased food consumption was noted in 2 animals on day 7. One animal was observed with unthrifty coat and ano-genital staining; and another animal had alopecia noted on the left hip.
Body weight:
As compared to starting body weights, 5 of 6 rabbits exhibited slight body weight decreased at day 7; with only 2 animals having decreased body weights at 14 days.
Gross pathology:
Postmortem gross examination revealed 1 animal with liver and salivary gland discoloration; 1 animal with discolored kidneys, enlarged spleen and hair ball in stomach; and 1 animal with alopecia in the abdominal area and slight brown staining of the ano-genital area. Three of the 6 test animals exhibited no observable abnormalities.
Other findings:
- Other observations: Two animals were noted with their collars off and one animal with collar in its mouth. This did not impact the outcome of this study.

Any other information on results incl. tables

Results tables can be found in the attachment to this RSS.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
LD50> 3160 mg/kg
Executive summary:

The acute dermal systemic toxicity of the test substance was evaluated in rabbits following topical occlusive exposure. Test material was applied as a single dose of 3160 mg/kg to the clipped backs of 3 male and 3 female rabbits. The test material remained in contact with the intact skin of all animals for a period of 24 hours. The amount of material remaining on the skin of each animal after the 24 hour exposure was estimated.

 

Observations were made as to the nature, onset, severity, and duration of toxicological signs 2 and 4 hours after dosing and once per day thereafter, for a total of 14 days. Dermal responses were evaluated 24 hours after topical application and on days 3, 7, 10 and 14 according to the draize method of scoring. Body weights were recorded on the day of dosing (day 0), day 7 and day 14. After the day 14 weighings and observations, all surviving rabbits were euthanized by intravenous administration of sodium pentobarbital, necropsies were performed on all animals by qualified personnel.

 

There were no animal deaths noted during the course gf the study. As compared to starting body weights 5 of the 6 rabbits exhibited slight body weight decreases at day 7; with only 2 animals having decreased body weights at 14 days.

 

Erythema was noted in all study animals and edema was noted in 4 of the 6 animals during the course of the study. Erythema scores ranged from slight i'o severe, and edema ranged from very slight to slight. All animals exhibited desquamation and 2 animals had eschar during the course of the study. Slight dermal irritation study, persisted in 4 of the test animals through termination of study.

 

Clinical in-life observations included 2 animals with food consumption decrease (day 7 only), 1 animal with unthrifty coat and ano-genital staining and 1 animal with alopecia.

 

Postmortem gross examination revealed liver and salivary gland discoloration in 1 animal; kidney discoloration and spleen enlargement in 1 animal and alopecia in 1 animal. Three of the 6 test animals exhibited no observable abnormalities.