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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September 13, 2013-October 24, 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Well documented study performed according to OECD guideline 425 and US EPA Health Effects Test Guidelines, OPPTS 870.1100. The deviation from the protocol had no impact on the overall results of the study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report date:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
The deviation from the protocol had no impact on the overall results of the study.
Qualifier:
according to guideline
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
yes
Remarks:
The deviation from the protocol had no impact on the overall results of the study.
GLP compliance:
yes
Remarks:
40 CFR 160: EPA GLP Standards: Pesticide Programs (FIFRA), 1989; OECD Principles of GLP (as revised in 1997) published in ENV/MC/CHEM (98)17, OECD, Paris, 19998; EC Directive 2004/10/EC, Official Journal of the European Union, L50/44, Feb. 20, 2004.
Test type:
up-and-down procedure
Limit test:
no

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: MA027180EXA026/ PSL Reference number: 130807-10H
- Expiration date of the lot/batch: November 20, 2018

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature
- Test item handling: The sample was administered as a 60% w/w mixture in distilled water.
- Stability under test conditions: Test item was expected to be stable for the duration of testing.
- Solubility and stability of the test substance in the solvent/vehicle: Soluble in water, methanol and acetone. The sample was administered as a 60% w/w mixture in distilled water. Preliminary sample preparation testing conducted by PSL, indicated that mixtures in excess of 60% (i.e., 70-85%) were too viscous to be administered properly. The test item was expected to be stable for the duration of testing.

OTHER SPECIFICS:
pH: 2.6 @ 0.133% dilution

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories, Inc.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: young adults, 9-12 weeks old.
- Weight at study initiation: 163-188 g
- Fasting period before study: Overnight
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors, which conform to the size recommendations in the most recent Guide for the Care and use of Laboratory Animals (Natl. Res. Council, 2011). Enrichment (e.g, toy) was placed in each cage. Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet (e.g. ad libitum): Harlan Teklad Global 16% Protein Roden Diet #2016. The diet was available ad libitum, except during fasting.
- Water (e.g. ad libitum): Filtered tap water was supplied ad libitum.
- Acclimation period: 8-27 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22 degrees C
- Humidity (%): 46-75%
- Air changes (per hr): 12-13
- Photoperiod (hrs dark / hrs light): 12 dark/12 light

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
distilled
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 60% w/w mixture in distilled water
- Amount of vehicle (if gavage): not indicated
- MAXIMUM DOSE VOLUME APPLIED: not indicated
Doses:
174 mg/kg, 550 mg/kg and 2,000 mg/kg
The test item was administered in sequence to animals: 174 mg/kg, 550 mg/kg, 2,000 mg/kg, 550 mg/kg, 174 mg/kg, 550 mg/kg, 174 mg/kg, 550 mg/kg, 174 mg/kg.
No. of animals per sex per dose:
4 females 174 mg/kg and 550 mg/kg; 1 female 2,000 mg/kg.
Control animals:
no
Details on study design:
Details on study design
- Duration of observation period following administration: 14 days or unitl death occurred.
- Frequency of observations and weighing: The animals were observed for mortality, signs of gross toxicity, and behavior changes during the first several hours post-dosing and at least once daily thereafter. Animals were weighed prior to test item administration and again on Days 7 and 14 following dosing or after death.
- Necropsy of survivors performed: yes. Surviving rats were euthanized via CO2 inhalation at the end of the 14-day observation period. Gross necroposies were performed on all decendents and euthanized animals. Tissues and organs of the thoracic and abdominal cavities were examined.
- Other examinations performed: Gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma.

Statistics:
The Acute Oral Toxicity (Guideline 425) Statistical Program (Westat, version 1.0, May 2001) was used for all data analyses iincluding: dose progression selections, stopping criteria determinations and /or LD50 and confidence limit calculations.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
approximate LD50
Effect level:
550 mg/kg bw
Based on:
test mat.
95% CL:
> 234 - <= 853
Remarks on result:
other: the one dose with partial response
Remarks:
The confidence interval is a profile-likelihood based confidence interval
Mortality:
Female dosing sequence 3 at 2,000 mg/kg; Females dosing sequence 4, 6 and 8 at 550 mg/kg.
Clinical signs:
174 mg/kg Dose Level: One animal was hypoactive and exhibited hunched posture, irregular respiration, reduced fecal volume and nasal discharge, but recovered by Day 6 and along with remaining animals appeared active and healthy for the remainder of the 14-day observation period.

550 mg/kg Dose Level: Three animals died within two days of test item administration. Prior to death, the animals exhibited abnormal posture, irregular respiration, reduced fecal volumne, oral discharge, hypoactivity, gasping and/or writhing. The surviving animal was hypoactive and exhibited hunched posture, irregular respiration and reduced fecal volumne, but recovered by Day 3 and appeared active and healthy, gaining body weight for the remainder of the 14-day observation period.

2,000 mg/kg Dose Level: The animal died within one hour of test item administration. There were no clinical sigs noted prior to death.
Body weight:
174 mg/kg Dose Level: All animals survived exposure and gained body weight during the study.

550 mg/kg Dose Level: The surviving animal recovered by Day 3 and gained body weight for the remainder of the 14-day observation period.
Gross pathology:
174 mg/kg Dose Level: No gross abnormalities were noted for the euthanized animals when necropsied at the conclusion of the 14-day observation period.

550 mg/kg Dose Level: Gross necropsy of the decedenets revealed distention of the stomach and intestines. No gross abnormalities were noted for the euthanized animal when necropsied at the conclusion of the 14-day observation period.

2,000 mg/kg Dose Level: Gross necropsy of the decedenets revealed distention of the stomach and intestines

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Under the conditions of the study, the acute oral LD50 of the test item is estimated to be 550 mg/kg of body weight (the one dose with partial response) in female rats with a 95% PL confidence interval of 234 mg/kg (lower) to 853 mg/kg (upper). Therefore, the substance is classified as Cat 4 under GHS.

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