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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May 12, 1998-May 26, 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
Well documented study performed according to Product Safety Labs' Protocol P322. Acute Dermal Toxicity Limit Test

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Remarks:
Reported as Product Safety Labs Protocol P322. Acute Dermal Toxicity Limit Test
GLP compliance:
yes
Remarks:
The study meets the requiremenmts of 40 CFR Part 160 with the following exception: The stability, characterization, identity and verification of the test item concentration as received and tested are the responsibility of the study sponsor.
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
1-[2-(allyloxy)ethyl-2-(2,4-dichlorophenyl)-1H-imidazolium hydrogen sulphate
EC Number:
261-351-5
EC Name:
1-[2-(allyloxy)ethyl-2-(2,4-dichlorophenyl)-1H-imidazolium hydrogen sulphate
Cas Number:
58594-72-2
Molecular formula:
C14H14Cl2N2O.H2O4S
IUPAC Name:
1-[2-(2,4-DICHLOROPHENYL)-2-(PROP-2-EN-1-YLOXY)ETHYL]-1H-IMIDAZOLE SULFATE (1:1)
Test material form:
solid: particulate/powder
Details on test material:
- Product names: FUNGAFLOR® 75C / FUNGAFLOR® 75SP / FUNGAZIL® 750SP / FUNGAFLOR® 75PS / FUNGAZIL® 75SP / FUNGAFLOR® 750SP
- Reference number: JNJ-2634372-ABI / R027180 (product code)
- Physical state: solid
- Appearance: beige solid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: ZR027180PUE331/PSL Code Number E80511-2H
- Expiration date of the lot/batch: October 15, 2003
- Purity test date: Imazalil base (75%), inerts (25%)

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature
- Stability under test conditions: Expected to be stable for the duration of testing.
- Solubility and stability of the test substance in the solvent/vehicle: Soluble in water (>500 g/L)

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Prior to application, the test item was moistened to achieve a dry paste by preparing a 90% w/w mixture in distilled water.
- Final preparation of a solid: The sample was applied as a 90% w/w mixture in distilled water.

Test animals

Species:
rabbit
Strain:
other: New Zealand albino
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Davidson's Mill Farm, South Brunswick, NJ
- Females (if applicable) nulliparous and non-pregnant: no data
- Age at study initiation: Young adult males and females
- Weight at study initiation: Males-2.3-2.6 kilograms; Females-2.2-2.5 kilograms
- Fasting period before study: no data
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors which confirm to the size recommendations in the Guide for the Care and use of Laboratory Animals DHEW (NIH) No. 86.23. Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet (e.g. ad libitum): Pelleted Purina Rabbit Chow #5326
- Water (e.g. ad libitum): Filtered tap water was supplied ad libitum by a automatic water dispensing system.
- Acclimation period: 19 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.3-22.2 °C
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Remarks:
distilled
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorsal area and trunk. On the day prior to application, a group of animals was prepared by clipping (Oster model #A2-small) the dorsal area and the trunk.
- % coverage: 4 in x 8 in area (approximately 10% of the body surface area)
- Type of wrap if used: The test material was applied to approximately to 4 in x 8 in area and covered with a 4 in x 8 in 6-ply gauze pad. The gauze pad and entire trunk of each animal were then wrapped with a 3 inch Durapore tape to avoid dislocation of the pad and to minimize loss of the test item. Elizabethan collars were placed on each rabbit and they were returned to their designated cages.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Test sites were gently wiped with water and a clean towel to remove residual test material.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bodyweight
- Constant volume or concentration used: yes
- For solids, paste formed: Yes, dry paste.

Duration of exposure:
24 h
Doses:
1
No. of animals per sex per dose:
5 males, 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations-1 and 3 hours after application of test item and at least once daily thereafater for 14 days or until mortality. Weighing-Days: On day prior to application and then on days 7 and 14.
- Necropsy of survivors performed: yes: All surviving animals were euthanized via sodium pentobarbital on Day 14. A gross necropsy was performed on the decedent and all euthanized animals. Tissues and organs of the thoracic and abdominal cavities were examined.
Statistics:
No statistical analysis was performed.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Dermal irritation (eschar and/or erythema and edema) were noted at the dose site of all animals between days 1 and 14.
Mortality:
One male (Male 4428) died within two days of test item application.
Clinical signs:
Male 4428: Toxic signs prior to death included irregular respiration, hypoactivity and prone posture.
With the exception of prone posture, the surviving rabbits exhibited similar clinical signs, as well as reduced food consumption and reduced fecal volume, but recovered by Day 8.

Dermal irritation (eschar and/or erythema and edema) was also noted at the dose site of all animals between Days 1 and 14.
Body weight:
Several animals (Male 4426, Female 4429, Female 4431) exhibited a loss of bodyweights at 7 days, however, all Day 14 bodyweights exceeded those recorded at initiation.
Gross pathology:
The gross necropsy of the decedent revealed discoloration of the lungs and injected veins of the intestines. Gross necropsy findings at terminal sacrifice were unremarkable. No gross abnormalities were noted for the animals necropsied at the conclusion of the study.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The Single Dose Acute Dermal LD50 of the test item is greater than 2,000 mg/kg of bodyweight.