(1,4,5,6-tetrahydro-4,6-dioxopyrimidin-2-yl)cyanamide

Endpoint summary

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1981

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

84/449/EEC

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

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 or test system 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:

other: No signs of systemic toxicity were noted during the study.

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