4,5-dihydroxy-1,3-dimethylimidazolidin-2-one

Endpoint summary

Description of key information

In the key Acute Oral Toxicity Study, the LD50 was >2000 mg/kg bw in male and female rats.

 

In the key acute dermal toxicity study, the LD50 was >3300 mg/kg bw in male and female rats. In a supporting study in male and female rats according to OECD guideline 402, the LD50 was >2000 mg/kg bw.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: EEC Directive 92/69, 1992

GLP compliance:

yes (incl. QA statement)

Remarks:

testing lab.

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Young adult male and female animals were used with a comparable body weight at the start of the study (150 g - 300 g). The animals were identified using cage cards and group identification was done by tail marking. The animals were housed in fully air-conditioned rooms with a central air-conditioning of 20 - 24°C for temperature and a relative humidity between 30 - 70%. The day/night rhythm was 12 h dark and 12 h light. Animals were housed single in stainless steel wire mesh cages with no bedding in the cages (sawdust in the waste trays). A standard laboratory diet was used and tap water was available ad libitum.

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Aqueous formulation corresponds to the physiological medium.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

Single oral administration by gavage (solution).
Observation period: 14 days
Acclimatization period of the animals: at least 1 week. The animals were given no feed at least 16 hours before administration, but water was available ad libitum.
Individually body weight determination shortly before application, weekly thereafter and at the end of the study (before fasting period).
Recording of signs and symptoms several times on the day of administration, at least once each workday for the individual animals.
A check for general observations and mortality was made twice each workday and once on weekends and on public holidays for general observations and for any dead or moribund animals.
Necropsy at the last day of the observation period. Withdrawal of food at least 16 hours before killing with CO2; then necropsy with gross-pathology examination. Necropsy of all animals that died before as soon as possible.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

none

Clinical signs:

other: none

Gross pathology:

no abnormalities

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

Reliable without restrictions

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

basic information given; scientifically acceptable

Principles of method if other than guideline:

In accordance with the techniques specified in the Regulations for the Enforcement of the Federal Hazardous Substances Act (Code of Federal Regulatioris, Title 16, Part 1500).

GLP compliance:

no

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

The rabbits were individually identified by means of numbered ear tags.
The rabbits were housed in individual stainless steel cages suspended above the droppings. Food, consisting of Purina Laboratory Chow, and water were available at all times. The animals were kept on a 12-hour light/12-hour dark cycle.
Weight range 2431 to 3000 gram.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The rabbits were acclimated to the laboratory for at least 10 days before being dosed. The dose was applied to the abdominal skin area from which the fur had been previously removed with electric clippers. The abdominal skin area of half of the rabbits in the group was abraded by making a series of longitudinal minor epidermal incisions placed two to three centimeters apart, using a hypodermic needle as a cutting tool. The abrasions were sufficiently deep to penetrate the epidermis but not to induce bleeding. The skin of the remaining rabbits in the group remained intact. An equal number of males and females were assigned to the intact skin and abraded skin sub-groups.
The undiluted sample was applied at a dosage level of 3.0 ml/kg of body weight. The sample was introduced into a sleeve of rubber dental damming which was wrapped around the trunk of the animal and secured with staples. An outer layer of gauze and tape was placed around the trunk of the animal. The rabbit was restrained for 24 hours in a Newmann harness.
At the end of the 24-hour exposure period the binder was removed and any unabsorbed sample remaining on the skin was removed by gentle sponging with a moistened towel.
Each rabbit was examined throughly for gross signs of systemic toxicity and dermal irritation.
All rabbits were maintained for 14 days following completion of the exposure period. Examinations for gross signs of systemic toxicity and dermal irritation were carried out at frequent intervals during this period. At the end of the 14-day observation period the rabbits were weighed, sacrificed by T-61 overdose, and a gross necropsy was performed on each animal.

Duration of exposure:

24 hours

Doses:

3.0 mL/kg

No. of animals per sex per dose:

10

Control animals:

no

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3 mL/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3 300 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

none

Clinical signs:

other: Upon removal of the binders from the animals, the exposed area and binder appeared dry with no sample apparent on any of the animals. This proved evidence of complete dermal absorption of the sample. Irritative effects noted during the study included eryt

Gross pathology:

Gross necropsies performed at the termination of the study revealed pitted kidneys in one animal. No other gross-pathological alterations or lesions were noted in any of the rabbits.

Body weight changes (dose level: 3.0 ml/kg):

Rabbit No.	Sex	Skin		Body weight
		Intact	Abraded	Start (gm)	Finish (gm)	Change (gm)
1	male	x		2691	2971	280
2	male		x	2964	3292	328
3	male	x		3000	3531	531
4	female		x	2998	3327	329
5	male	x		2940	3069	129
6	male		x	2995	3215	220
7	female	x		2999	3302	303
8	female		x	2599	2709	110
9	female	x		2431	3024	593
10	female		x	2775	3145	370

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 3 300 mg/kg bw

Quality of whole database:

Study well documented, meets generally accepted scientific principles, acceptable for assessment

Additional information

Key, Acute oral toxicity, RL1

BASF (1995) reported an acute oral LD50 value of > 2000 mg/kg for male and female rats. Wistar rats were administered (gavage) a aqueous formulation of the test chemical in a concentration of 2000 mg/kg. No mortalities and no clinical signs were reported. Necropsy of the surviving animals showed no abnormalities.

 

For acute inhalation toxicity only an orientating information is available which is not used for classification.

Key, Acute inhalation toxicity, RL2

BASF (1973) reported an inhalation hazard test with Fixapret CPN (CAS: 1854-26-8). Inhalation exposure for 8 h to an atmosphere enriched with test substance vapors from a 45% aqueous solution of the test substance (conc. 6.93 mg/L) at 20°C caused no mortalities and no adverse systemic effects in rats, but some signs of dyspnea and irritation of mucous membrane.

 

Supporting, Acute inhalation toxicity, RL2

The Springborne Institute (1980) reported about an inhalation safety screen of Textile Resin NFU in rats. Male and female Harlan rats were offered an inhalation vapour for 1 hour (no data about the concentration). No mortalities and no gross-pathological findings were reported. Clinical signs were nasal irritation during the early parts of exposure (animals appearaed normal during most of the exposure and for the next 14 days).

 

Key, Acute dermal toxicity, RL2

Hill Top Research Inc. (1979) reported about the acute dermal toxicity of Textile NFU. Male and female New Zealand White rabbits were covered occlusive with the undiluted test substance for 24 hours. The concentration used was 3 mL/kg (3300 mg/kg bw). No mortalities were seen. The irritative effects noted during the study included eythema, atonia and desquamation. Gross necropsies performed at the termination of the study revealed pitted kidneys in one animal. No other gross-pathological alterations or lesions were noted in any of the animal. The acute dermal LD50 value was found to be > 3300 mg/kg bw.

 

Supporting, Acute dermal toxicity, RL2

BASF (2009) reported an acute dermal toxicity study with the structure-related compound Fixapret CP (CAS: 92908-35-5). In this experiment, male and female Wistar rats were covered semiocclusive with the test substance for 24 hours. The concentration used was 2000 mg/kg. No mortalities, no clinical signs and no gross-pathological changes were noted. Local effect: slightly yellowish discoloration of the applicate site. The acute dermal LD50 value was > 2000 mg/kg bw.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data, the test item is not classified and labelled for acute toxicity according to Regulation (EC) No 1272/2008 (CLP), as amended for the eighteenth time in Regulation (EU) 2022/692.