Pyrimidine, 2-ethoxy-4,6-difluoro-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The test material was administered as a single dose via gavage to three female Fischer 344 rats per dose level. Animals were observed for two weeks post-exposure.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-ethoxy-4,6-difluoropyrimidine

EC Number:

692-762-1

Cas Number:

166524-65-8

Molecular formula:

C6H6F2N2O

IUPAC Name:

2-ethoxy-4,6-difluoropyrimidine

Test material form:

other: liquid (unspecified)

Details on test material:

- Name of test material (as cited in study report): 2-Ethoxy-4,6-difluoropyrimidine
- Appearance: clear liquid
- pH: 3.0

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 12 weeks
- Weight at study initiation: 129.5 - 146.3 g
- Fasting period before study: Yes. All animals were fasted the night before treatment. Feed was provided to animals following test material administration.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: unchanged or in 0.5 % methocel

Details on oral exposure:

Rats received 50 or 100 mg/kg as a 10 % solution in 0.5 % methocel or 500, 1000 or 2000 mg/kg of neat test material by single-dose oral gavage.

Doses:

50, 100, 500, 1000 and 2000 mg/kg bw.

No. of animals per sex per dose:

3 females per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: individual body weights were recorded on test day 1, 2, 8 and 15
- Necropsy of survivors performed: no data
- Other examinations performed: mortality and clinical signs

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

50 - 500 mg/kg bw

Based on:

test mat.

Mortality:

At 1000 and 2000 mg/kg, all three animals were dead within three hours of dosing. At 500 mg/kg, all three animals were dead within six hours of dosing.
At the 100 mg/kg dose level, one animal out of three died by test day two. All animals survived the test period at the 50 mg/kg dose level.

Clinical signs:

other: Clinical signs indicative of systemic toxicity in the 2000, 1000 and/or 500 mg/kg dose levels consisted of salivation, severe lacrimation, chromorhinorrhea, faecal soiling, loose stool, decreased activity, lateral recumbency, incoordination and muscle twi

Any other information on results incl. tables

Table 1: Individual Rat Body Weights (g)

Dose Level (mg/kg)	Animal Number	Test Day
		1	2	8	15
100	93A6466	138.0	-	-	-
	93A6467	137.1	139.3	156.3	159.2
	93A6468	139.3	138.8	150.8	159.7
50	93A6469	145.8	147.8	166.9	175.1
	93A6470	142.4	146.0	161.7	171.6
	93A6471	129.5	135.2	150.2	154.1

- = Dead animal

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category III

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study, the acute oral LD50 of the test material was estimated to be between 50 and 500 mg/kg bw. As such, the test material is classified as Category 3 in accordance with EU criteria.

Executive summary:

A study was conducted to investigate the acute oral toxicity potential in female Fischer 344 rats.

Three fasted female rats per dose level received 50 or 100 mg/kg as a 10 % solution in 0.5 % methocel or 500, 1000 or 2000 mg/kg of the neat test material by single-dose oral gavage. Animals were observed for two weeks following test material administration.

At 1000 and 2000 mg/kg, all three animals were dead within three hours of dosing. At 500 mg/kg, all three animals were dead within six hours of dosing. At the 100 mg/kg dose level, one animal out of three died by test day two. All animals survived the test period at the 50 mg/kg dose level.

Clinical signs indicative of systemic toxicity in the 2000, 1000 and/or 500 mg/kg dose levels consisted of salivation, severe lacrimation, chromorhinorrhea, faecal soiling, loose stool, decreased activity, lateral recumbency, incoordination and muscle twitches. Clinical signs indicative of systemic toxicity at the 100 mg/kg dose level consisted of salivation, lacrimation, chromorhinorrhea, urine soiling and decreased activity. Signs of toxicity began within an hour of dosing through test day two. Both surviving animals from the 100 mg/kg dose group were observed as normal from test day three through the remainder of the observation period. All animals given 50 mg/kg had salivation one hour after dosing and were observed as normal through the remainder of the observation period.

Administration of the test material had no effect on body weight during the two week observation period.

Under the conditions of the study, the acute oral LD50 of the test material was estimated to be between 50 and 500 mg/kg bw. As such, the test material is classified as Category 3 in accordance with EU criteria.