Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
31.08.1988 - 14.09.1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPP 81-2 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
other: Limit-test
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:

- Physical state: greyish-green powder
- Analytical purity: 100%
- Lot/batch No.: 3883559 A
- Storage condition of test material: room temperature

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazleton-Dutchland Laboratory Animals, Denver, Pennsylvania.
- Age at study initiation: young adults (at least 8 weeks old).
- Weight at study initiation: males: 2,5 - 2,7 kg; females: 2,7 - 2,9 kg.
- Housing: individually.
- Diet: Lab Rabbit Chow HF (Purina #5326), 125 g/day while on test.
- Water: tap water, ad libitum.
- Acclimation period: 44 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 21 °C
- Humidity (%): 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

Administration / exposure

Type of coverage:
occlusive
Vehicle:
physiological saline
Details on dermal exposure:
TEST SITE
- Area of exposure: 4" x 12"
- Type of wrap if used: impervious plastic sheet

REMOVAL OF TEST SUBSTANCE
- Washing (if done): only wiped free of excess test material with dry paper towels.
- Time after start of exposure: 24 h

TEST MATERIAL
- For solids, paste formed: the dry material was placed direct on a gauze and moistened with 7 mls of saline

VEHICLE
- Amount(s) applied (volume or weight with unit): 7 ml
Duration of exposure:
24 h
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations: twice daily.
- Frequency of weighing: pretest (time of clipping), predose, days 7 and 14.
- Necropsy of survivors performed: yes.
- Other examinations performed: clinical signs, body weight.
Statistics:
no statistics performed.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
No mortality occured.
Clinical signs:
Local signs: Two males exhibited severe dermal effects at a small area of the dose site (necrosis followed by eschar formation, and exfoliation of the eschar tissue) which persisted throughout the study.

Systemic toxicity: All animals were free of significant signs of systemic toxicity; only single occurrences of nasal discharge, ocular discharge and fecal staining.
Body weight:
All animals exhibited a slight weight loss or no weight change by day 7, but most gained weight between day 7 and 14.
Gross pathology:
Gross postmortem observations confirmed the presence of dermal lesions. Other observations were similar to those seen in control animals or were considered to represent normal physiological variation.

Applicant's summary and conclusion