α,α-diphenylpiperidine-4-methanol hydrochloride

Acute Toxicity: oral

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

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

Test material information

Constituent 1

Reference substance name:

Azacyclonol

EC Number:

204-092-5

EC Name:

Azacyclonol

Cas Number:

115-46-8

IUPAC Name:

diphenyl(piperidin-4-yl)methanol

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 or test system 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- Fasting period before study: Food was withdrawn 18 hours before dosing and redistributed approximately 4 hours after administration of the test substance.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 levels

Effect levels 1

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

Effect levels 2

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:

other: 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 o

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.