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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12th August 1991 to 26th August 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report date:
1993

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EPA OPP 81-2 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
EPA OTS 798.1100 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Propargite
EC Number:
219-006-1
EC Name:
Propargite
Cas Number:
2312-35-8
Molecular formula:
C19H26O4S
IUPAC Name:
propargite
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): Omite® Technical
- Stability under test conditions: at least one year at room temperature
- Storage condition of test material: sealed container at room temperature

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hazelton Research Products, Inc., Denver, Pennsylvania, USA
- Age at study initiation: young adult
- Weight at study initiation: 2097-2231 g
- Housing: individual suspended mesh-bottom cages
- Diet: Purina® Certified Rabbit Chow® #5322 ad libitum
- Water: tap water ad libitum
- Acclimation period: a minimum of 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 67-76 ºF
- Humidity: 62-80 %
- Photoperiod: 12 hours light/12 hours dark

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- % coverage: approximately 23 %
- Type of wrap if used: gauze binders

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 3.7 mL/kg
Duration of exposure:
24 hours
Doses:
4000 mg/kg bw
No. of animals per sex per dose:
Five
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality and clinical observations at 1, 3, 4 hours post-dose and thereafter twice daily; dermal observations approximately 30-60 minutes after bandage removal and daily thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: body weights on days 0, 7 and 14

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 4 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
Abnormal defecation was generally noted during the first week post treatment. Loss of appetite was noted for six animals, while scabbing/swelling around the mouth and dry yellow staining around the nose were observed for eight animals. By the end of the study four animals appeared normal. The test material caused significant signs of irritation (erythema, oedema, eschar, desquamation and exfoliation).
Body weight:
Two males exhibited a loss in body weight from day 0 to day 7, but these animals regained the lost weight and surpassed their day 0 body weight by the end of the study. There were no other remarkable body weight changes during the study.
Gross pathology:
The only finding on necropsy was reddened lungs in a single male.

Applicant's summary and conclusion

Interpretation of results:
other: Not classified in accordance with EU criteria
Conclusions:
The acute dermal LD50 of the test material in rabbits is greater than 4000 mg/kg.
Executive summary:

The test material was administered once dermally at a dose of 4000 mg/kg to the shaved intact skin of five male and five female albino rabbits for a 24 hour period under semi-occlusive dressing. Mortality, clinical observations, dermal findings, body weights and gross necropsy findings were evaluated.

There were no deaths or remarkable body weight changes during this study.

Two animals vocalised at the time of bandage and test material removal. Abnormal defecation was generally noted during the first week of the study. Inappetence was observed early in the study for six animals. Scabbing and swelling around the mouth and dry yellow staining around the nose were each noted for eight animals during the second week of the study. One animal had wet yellow urogenital staining. Four animals appeared normal by study termination or earlier.

The test material induced severe erythema and edema on all animals. Additional dermal observations generally appeared during the second week of the study and persisted through to study termination. These findings included eschar, white-yellow areas present within the application site, fissuring and desquamation for all animals. Six animals had white-yellow exudate on the application site. Exfoliation was observed on four sites late in the study.

Thickened skin and desquamation within the application site were noted for all animals at terminal necropsy. One animal had reddened lungs. There were no other remarkable gross necropsy findings.

The LD50 value was found to be greater than 4000 mg/kg.

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