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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD, GLP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
This type of study is no longer part of the OECD guidelines for the Testing of Chemicals
GLP compliance:
yes
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid - liquid: suspension
Details on test material:
- Name of test material (as cited in study report): Azacyclonol-Base
- Physical state: whitish granular powder
- Purity: 98.3 % (w/w)
- Impurities (identity and concentrations): included in the certificate of analysis
- Batch No.: 86000298
- Storage conditions: at +4°C and protected from Iight
- Date of receipt: 31 October 1997
- A certificate of analysis is included in the report.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Iffa Crédo, Domaine des Oncins, 69210 L’Arbresle, France
- Number and sex: Two males and two females were used for the preliminary test and three groups of five males and/or five females each for the main test.
- Age at initiation of treatment: 6 weeks
- Weight at initiation of treatment: Male: 182 ± 8 g; Female: 149 ± 10 g
- Fasting period before study: Food was withdrawn 18 hours before dosing and redistributed approximately 4 hours after administration of the test substance.
- Housing: housed in polycarbonate cages (48 cm x 27 cm x 20 cm). 4 to 7 animals of the same sex during the acclimatization period and 5 rats of the same sex during the treatment period. Each cage contained dust-free sawdust (SICSA).
- Diet (e.g. ad libitum): controlled pelleted rodent diet (AO4 C, U.A.R.) ad libitum.
- Water (e.g. ad libitum): filtered by a F.G. Millipore membrane (0.22 micron)
- Acclimatization period: 5 days before treatment

ENVIRONMENTAL CONDITIONS
- Temperature: 21 ± 2 ° C
- Relative Humidity: 30 to 70%
- Ventilation: 12 cycles/hour of filtered, non-recycled air
- Light/dark cycle: 12/12 hours



Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5% methylcellulose aqueous solution
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Suspension in a 0.5% methylcellulose aqueous solution
- Administration volume: 10 mL/kg
Doses:
Preliminary study: 1000 and 2000 mg/kg
Main study: 750, 1000 and 1300 mg/kg
No. of animals per sex per dose:
Preliminary study: 2 rats/sex/dose
Main study: 5 rats/males/dose and 5 females rats for 1000 mg/kg
Control animals:
other: Historical controls from October 1994 to December 1996.
Details on study design:
- Treatment frequency: Once, a single administration on day 1 (D1)
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing:
= Clinical signs: daily observations
= Body weight (D1, 8, 15)
- Necropsy of survivors performed: yes at D15
Statistics:
The 70 to 95 % confidence interval limits were calculated statistically according to Fieller's method ( 1944).

Results and discussion

Preliminary study:
At the 2000 mg/kg dose-level: animals died on day 1 or 2; sedation or hypoactivity, tremors and piloerection were noted prior to death.
At the 1000 mg/kg dose-level: sedation or hypoactivity, tremors, dyspnoea and piloerection were observed in both animals on days 1 and 2. No mortality occurred. Recovery was complete on day 3.
Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
984 mg/kg bw
Based on:
not specified
Remarks on result:
other: Determination of LD50 with 70% confidence interval limits
Sex:
female
Dose descriptor:
LD50
Effect level:
> 1 000 mg/kg bw
Based on:
not specified
Mortality:
No mortality was recorded among the females (1000 mg/kg).
In males, mortality was 100%, 60% and 0% in the 1300, 1000 and 750 mg/kg dose-groups, respectively. Mortality occurred between day 2 and day 8.
Clinical signs:
At 1300 mg/kg dose-level: hypoactivity, piloerection and tremors in all males from day 1. Dyspnoea, sedation and lateral recumbency in one animal prior to death.
At 1000 mg/kg dose-level: Sedation or hypoactivity, tremors and piloerection in all animals on day 1; lateral recumbency in one animal. Hypoactivity and piloerection persisted in the surviving animals on day 2; recovery was complete on day 3.
At 750 mg/kg dose-level:hypoactivity, tremors and piloerection in all animals on day 1; dyspnoea in one animal between day 2 and day 5. No other clinical signs and no mortality were noted.
Body weight:
No treatment-related changes for females (1000 mg/kg).
Body weight gain of the treated males given 1000 or 750 mg/kg was reduced between day 1 and day 8 compared to historical control values; it returned to normal thereafter.
Gross pathology:
No treatment-related changes.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 determined experimentally was 984 mg/kg in male. Toxicity was lower in females, concentration level of 1000 mg/kg bw did not induce any adverse effects. According to the 1272/2008 CLP regulation, the substance is classified category 4 for acute oral toxicity.