Hydroxyl-2-pyridone

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April 6, 1994-May 4, 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: US EPA FIFRA Pesticide Assessment Guidelines

Version / remarks:

1984

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hydroxyl-2-pyridone

EC Number:

212-506-0

EC Name:

Hydroxyl-2-pyridone

Cas Number:

822-89-9

Molecular formula:

C5H5NO2

IUPAC Name:

1-hydroxy-1,2-dihydropyridin-2-one

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study reports): Oxy PYRION
- Physical state: solid (powder)
- Appearance: white speckled gold powder

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 93100020

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature, glass jar
- Stability under test conditions: stable

Test animals

Species:

rat

Strain:

other: CD strain, remote Sprague-Dawley origin

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Limited, Margate, Kent, England
- Females (if applicable) nulliparous and non-pregnant: [yes/no] not specified
- Age at study initiation: young rats, approximately 5 weeks old.
- Weight at study initiation: Males-103-154 g; Females 104-132 g
- Fasting period before study: 24 h prior to dosing
- Housing:Stainles steel grid cages, 5 per cage, same sex
- Diet (e.g. ad libitum): Pelleted rodent diet, Special Diets Services Limited, Witham, Essex, England, ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period:5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 degrees C
- Humidity (%): 40-70%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 dark/12 light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 0.5% methylcellulose

MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg

Doses:

800, 1265, 2000, and 5000 mg.kg

No. of animals per sex per dose:

5 males, 5 females, 800 mg/kg; 5 females, 1265 mg/kg; 5 males, 5 females, 2000 mg/kg; 5 males, 5000 mg/kg.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were made 3 times in the first hour, 2 more in day 1, and then 2 inspections and 1 recording daily thereafter. Weighed the day before dosing, and days 1, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

LD50 calculations were conducted via Probit analysis.

Results and discussion

Preliminary study:

Yes. 1 male, 1 female each dose, at 400, 800, and 1000 mg/kg.

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 723 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 205 - <= 2 241

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

1 765 mg/kg bw

Based on:

test mat.

95% CL:

>= 820 - <= 2 709

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

1 596 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 228 - <= 1 964

Mortality:

1 female at 1265 mg/kg, 2 males, 4 females at 2000 mg/kg, 5 males at 5000 mg/kg:
mortality males and females: 0/1 at 400 mg/kg
mortality males 1/1 and females 0/1 at 800 mg/kg
mortality males 1/1 and females 1/1 at 2000 mg/kg

Clinical signs:

Ante mortem signs comprised underactivity, prone position, pallor, clonic or tonic convulsions, muscle spasticity, muscle tremor, pigmented orbital secretion and salivation.
Signs of reaction to treatment in the surviving animals comprised underactivity, staggering gait, muscle tremor, muscle fasciculations, piloerection, hairloss and hunched posture. The majority of animals were overtly normal from day 2, although two male animals treated at 800 mg/kg showed hairloss throughout the second week of the observation period.

Body weight:

Surviving animals achieved expected body weight gains over the course of the study.

Gross pathology:

Necropsy revealed no sinificant macroscopic lesions.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The test substance was found to have an LD50 of 1723 mg/kg in both sexes of rats, with a 95% confidence level of 1205-2241 mg/kg. Therefore, the substance is classified as Cat 4 under GHS.