5-Diazo-2,4,6(1H, 3H, 5H)-pyrimidinetrione

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: Guidelinestudy and GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

5-Diazo-2,4,6(1H, 3H, 5H)-pyrimidinetrione

EC Number:

608-591-2

Cas Number:

31221-06-4

Molecular formula:

C4H2N4O3

IUPAC Name:

5-Diazo-2,4,6(1H, 3H, 5H)-pyrimidinetrione

Details on test material:

content 96.9 %, orange solid

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 158-197 g
- Fasting period before study: 16-24 hours
- Housing: group caged
- Diet ad libitum
- Water ad libitum
- Acclimation period: at least 5 days

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

I

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: the test item was formulated in tap water with the help of 2 % Cremophor EL

Details on oral exposure:

the test item was tested using a stepwise procedure, each step using three animals of a single sex.
the dose level to be used as the starting dose should be that which is most likely to produce mortality in some of the dosed animals

Doses:

starting dose: 2000 mg/kg bw; if mortality occur next dose is 300 mg/kg bw next steps would be 50 and 5 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

the test item was tested using a stepwise procedure, each step using three animals of a single sex.
the dose level to be used as the starting dose should be that which is most likely to produce mortality in some of the dosed animals
absence or presence of compound-related mortality of the animals dosed at one step determined the next step.i.e.:
no further testing is needed
doseing of three additional animals, with the same dose
dosing of three additional animals at the next higher or the next lower dose level

Statistics:

no

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Mortality:

--2000 mg/kg bw:
3/3 time of death: 2 d - 7 d (2/3 had to be killed moribund and 1/3 died during the observation period)
--first trial: 300 mg/kg bw: 0/3
-- second trial: 300 mg/kg bw: 0/3

Clinical signs:

--2000 mg/kg bw
piloerection, abdominal posititon, temporary creeping gait, labored breathing, narrowed palpebral fissure, pallor cyanosis, sinken flanks, uncoordinated gait, poor general condition, decreased motility, and hunched posture
300 mg/kg bw
was tolerated with clinical signs

Body weight:

300 mg/ kg bw
was tolerated without effects on weight gain

Gross pathology:

2000 mg/kg bw:
cloudy and hemorrhagic change-in-contents of intestine, black discolored liver, hemorrhagic change-in-content of urinary bladder and pale kidneys
300 mg/kg bw
was tolerated without pathological findings

Other findings:

no further data

Applicant's summary and conclusion

Executive summary:

Diazobarbitursäure was tested for acute oral toxicity in female Wistar rats according to OECD TG 423.resulting in a LD50 ranging between 2000 and 300 mg/kg bw. 2000 mg/kg bw caused clear clinical signs of toxicity and the death of 3/3 rats within 7 days whereas 300 mg/kg bw was tolerated without any pathological findings and the animals survived until the end of the observation time.