4,6-Dichloro-5-fluoropyrimidine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2001-08-09 to 2002-08-26

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

22 March 1996

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

1

Reference substance name:

-

EC Number:

446-560-3

EC Name:

-

Cas Number:

213265-83-9

Molecular formula:

C4HCl2FN2

IUPAC Name:

4,6-dichloro-5-fluoropyrimidine

Test animals

Species:

rat

Strain:

Wistar

Remarks:

HsdCpb:WU

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, District of Paderborn
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: males approx. 10 weeks and females approx. 9 weeks
- Weight at study initiation: males: 242-266 g; females: 172-188 g
- Fasting period before study: not reported
- Housing: grouped, conventionally in polycarbonate cages; the bedding consisted of low-dust wood granules type BK 8/15 (supplier: Ssniff, Spezialdiäten GmbH, Soest/Westphalia).
- Diet (e.g. ad libitum): ad libitum, "NAFAG Ò No. 9441 W 10" (manufacturer: Eberle Nafag AG, Gossau)
- Water (e.g. ad libitum): ad libitum, tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22° +/- 2°C
- Humidity (%): 55 +/- 5
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: The test substance was formulated in demineralized water with the aid of 2 % Cremophor EL before administration.

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200, 20 and 2.5 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw


CLASS METHOD (if applicable) acute toxic class
- Rationale for the selection of the starting dose: as required by the test guideline

Doses:

2000, 200 and 25 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The body weights of the rats are recorded on day 1 before administration and then weekly.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Classification is based on cut-off values as indicated in the OECD guideline.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 30 - < 50 mg/kg bw

Based on:

test mat.

Mortality:

All animals of the 2000 mg/kg bw and the 200 mg/kg bw group died within 5 to 50 min and 20 min to 2 h, respectively.

Clinical signs:

irregular respiration

observations of tremors

salivation

other:

Body weight:

other body weight observations

Remarks:

The body weight and the body weight development of males and females were not affected by the treatment.

Gross pathology:

In animals that died during the observation period the following changes were detected:
Dark-red discoloration of liver
Slightly collapsed lung
Pale discoloration of kidneys
Pale discoloration of spleen
No gross pathologic changes were observed in animals sacrificed at the end of the study period.

Applicant's summary and conclusion

Interpretation of results:

Category 2 based on GHS criteria

Conclusions:

In the present study conducted according to OECD test guideline 423 (1996) three animals were administered a single dose of either 2000, 200 or 25 mg/kg bw of the test substance and observed for further 14 days. All animals of the 2000 mg/kg bw and the 200 mg/kg bw groups died at least within 2h. None of the animals of the 25 mg/kg bw group died, thus the LD50 value was determined at > 30 < 50 mg/kg bw.

Executive summary:

In an acute oral toxicity study according to OECD guideline 423, adopted 22 March 1996, 6 female, fasted, 9 weeks old Wistar strain rats and 3 male, fasted, 10 weeks old Wistar strain rats were given a single oral dose of 4,6-dichlor-5-fluorpyrimidinbe in demineralized water containing 2% Cremophor by gavage at a dose of 2000, 200 (females) and 25 mg/kg bw (males and females) and observed for 14 days.

6/6 animals of the 2000 and 200 mg/kg bw groups died 50 min and 2h after dosing, respectively. Clinical signs shown by the animals found dead included decreased, uncoordinated gait, labored breathing, increased salivation, narrowed palpebral fissures, and temporary tremor,. lateral position, temporary convulsions, reddened skin, increased motility, and tachypnea.

A dose of 25 mg/kg body weight was tolerated by male and female rats without mortalities and clinical signs.

The body weight and the body weight development of males and females were not affected by the treatment.

In animals that died during the observation period the following changes were detected:

Dark-red discoloration of liver

Slightly collapsed lung

Pale discoloration of kidneys

Pale discoloration of spleen

No gross pathologic changes were observed in animals sacrificed at the end of the study period.

Oral LD50 (rat, combined) > 30< 50 mg/kg bw