Registration Dossier

Administrative data

Description of key information

A study was performed to assess the acute oral toxicity of the (1,4,5,6-Tetrahydro-4,6-dioxopyrimidin-2-yl)cyanamide in the Sprague-Dawley strain rat according to guideline OECD 401 of 1981 and Method B1 of Commission Directive 84/449/EEC. Following a range-finding study, a group of ten fasted animals (five males and five females) was given a single oral dose of test material, as a suspension in distilled water B.P. at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the day of dosing and were then killed for gross pathological examination. There were no deaths, no signs of systemic toxicity nor any abnormalities noted at necropsy. The acute oral median lethal dose (LD50) of (1,4,5,6-Tetrahydro-4,6-dioxopyrimidin-2-yl)cyanamide in the Sprague-Dawley strain rat was found to be greater than 2000 mg/kg bodyweight.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 27 November 1991 to 14 January 1992.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1981
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
84/449/EEC
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Test material information:
Composition 1
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Description: off-white powder
- Sponsor's identification: CYDI


STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:
room temperature
- Container: white plastic jar (x2)
- Data relating to the identity, purity and stability of the test material are the responsibility of the sponsor.


Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:
Charles River (UK) Ltd., Mansion, Kent, U.K.
- Age at study initiation:
approximately five to eight weeks old
- Weight at study initiation: the males weighed 140 - 178g and the females 131 - 170g
- Fasting period before study:
overnight fast immediately before dosing and for approximately two hours after dosing
- Housing:
groups of up to five by sex in solid-floor polypropylene cages with sawdust bedding
- Diet (e.g. ad libitum):
Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, Essex, U.K.; free access throughout the study
- Water (e.g. ad libitum):
Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, Essex, U.K.; free access throughout the study
- Acclimation period:
at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
20-22°C
- Humidity (%):
52-65%
- Air changes (per hr):
approximately 15 changes per hour
- Photoperiod (hrs dark / hrs light):
12 hours continuous light and 12 hours darkness
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/ml
- Amount of vehicle (if gavage):10 ml/kg
- Lot/batch no. (if required): 1s2002

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg

All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.
Doses:
2000 mg/kg
No. of animals per sex per dose:
Range-finding study: 1
Main study: 5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 30 min, 1h, 2h and 4 h after dosing and subsequently once daily for 14 days
- Frequency of observations and weighing: Individual bodyweights were recorded prior to dosing on Day 0 and on Days 7 and 14.
- At the end of the study the animals were killed by cervical dislocation and subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Statistics:
Data evaluations included the relationship, if any, between the animals' exposure to the test material and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects.
Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test material was made.
The results were interpreted according to the Commission Directive 83/467/EEC which adapts Council Directive 67/548/EEC on the regulations relating to the classification, packaging and labelling of dangerous substances (see Table 1 below). Test materials with acute oral LD 50 values greater than 2000 mg/kg require no symbol and risk phrase.
Preliminary study:
A range-finding study was performed to determine a dosing regime. 1 male and 1 female rat were administered 10 ml/kg substance (dose level: 2000 mg/kg).
All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.
Deaths and overt signs of toxicity were recorded 30 min, 1h, 2h and 4 h after dosing and then daily for five days.
Individual bodyweights were recorded on the day of dosing to allow calculation of individual treatment volumes. No necropsies were performed.
Based on the results of the preliminary range-finding study, the dose level of 2000 mg/kg bodyweight was selected for the main study.
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted during the study.
Body weight:
All animals showed expected gain in bodyweight during the study (Table 2).
Gross pathology:
No abnormalities were noted at necropsy.

Table 2. Individual bodyweights and weekly bodyweight gain in the main study in the rats

Dose Level mg/kg

Animal Number & Sex

 Bodyweight (g) at Day

0                   7                       14                           

Bodyweight Gain (g) During week

1                        2

2000

505 Male

178

265

327

87

62

506 Male

161

221

297

60

76

507 Male

166

249

310

83

61

508 Male

140

209

262

69

53

509 Male

155

233

285

78

52

510 Female

170

225

260

55

35

511 Female

131

186

202

55

16

512 Female

141

215

245

74

30

513 Female

132

172

190

40

18

514 Female

140

172

196

32

24

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral median lethal dose (LD50) of (1,4,5,6-Tetrahydro-4,6-dioxopyrimidin-2-yl)cyanamide in the Sprague-Dawley strain rat was found to be greater than 2000 mg/kg bodyweight.
Executive summary:

A study was performed to assess the acute oral toxicity of the (1,4,5,6-Tetrahydro-4,6-dioxopyrimidin-2-yl)cyanamide in the Sprague-Dawley strain rat according to guideline OECD 401 of 1981 and Method B1 of Commission Directive 84/449/EEC. Following a range-finding study, a group of ten fasted animals (five males and five females) was given a single oral dose of test material, as a suspension in distilled water B.P. at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the day of dosing and were then killed for gross pathological examination. There were no deaths, no signs of systemic toxicity nor abnormalities noted at necropsy. The acute oral median lethal dose (LD50) of (1,4,5,6-Tetrahydro-4,6-dioxopyrimidin-2-yl)cyanamide in the Sprague-Dawley strain rat was found to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Justification for classification or non-classification