Tetrahydro-1,3,4,6-tetrakis(hydroxymethyl)imidazo[4,5-d]imidazole-2,5(1H,3H)-dione

Endpoint summary

Description of key information

LD50, oral, rat > 5000 mg/kg (mortality: 2/10)

LD50, i.p., mouse > 2000 mg/kg (mortality: 2/10)

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:

1978-1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

fixed dose procedure

Limit test:

no

Specific details on test material used for the study:

test substance no. 78/15
administration of a solution, test substance dissolved in aqua dest.

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Wiga
- Weight at study initiation: male animals 260 - 290 g, female animals 200 - 210 g
- Fasting period before study: 15 - 20 h before administration
- Diet (e.g. ad libitum): Herilan MRH-Haltung; Eggersmann KG

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50 % (w/v); 21.5 % (w/v)

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight

Doses:

2150 mg/kg and 5000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
mortality: 1 h, 1 d, 2 d, 7 d and 14 d after administration
mean weight: beginning of test, 2 - 4 d, 7 d, 13 d
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, necropsy findings, mortality

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 2/10 dead animals

Mortality:

20 % in high dose (2 dead male animals 1 day after administration),
no mortality observed in low dose

Clinical signs:

other: piloerection and dyspnea in high dose group spastic gait, diarrhea, apathy and poor general state in both treatment groups

Gross pathology:

animals that died:
heart: acute dilatation, acute passive hyperemia
lungs: slight acute emphysema
stomach: dilated, glandular stomach, slightly reddened
intestines: atonic, vessels considerably injected
sacrificed animals:
organs: no abnormalities detected

Table 1: LD50 determination

Doses [mg/kg]	No. of animals	Dead animals after 14 days	Mortality [%]	Doses used for calculating LD50
2.150	10	0	0
5.000	10	2	20.0	*

Table 2: Mean weight

Dose [mg/kg]		5.000	2.150
	Mean weight [g]
Male animals	Beginning of test	290	260
	After 2 – 4 d	314	287
	After 7 d	332	309
	After 13 d	359	329
Female animals	Beginning of test	210	200
	After 2 – 4 d	221	209
	After 7 d	229	222
	After 13 d	235	232

Interpretation of results:

GHS criteria not met

Conclusions:

It can be concluded that in this study the LD50 for the test substance is above 5.000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Remarks:

pre-guideline study; inhalation hazard assay

Qualifier:

no guideline followed

Version / remarks:

Inhalation hazard test based on H.F. Smyth et al.: Am.Ind.Hyg.Ass.J. 23, 95 - 107 (1962)

Principles of method if other than guideline:

- Principle of test: inhalation of an atmosphere enriched with volatile components at 20 °C
- Short description of test conditions: for enrichment, 200 L air/h was conducted through a layer of 5 cm of the product
- Parameters analysed / observed: lethality, clinical signs, necropsy findings

GLP compliance:

no

Test type:

fixed concentration procedure

Species:

rat

Strain:

not specified

Sex:

male/female

Route of administration:

inhalation: vapour

Type of inhalation exposure:

not specified

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Source and rate of air: 200 L air/h
- Temperature in air chamber: 20 °C

Duration of exposure:

7 h

Concentrations:

app. 13mg/L

No. of animals per sex per dose:

12 in total
(3 male and 3 female animals per experiment, 2 repetitions)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Sex:

male/female

Dose descriptor:

LC0

Effect level:

>= 13 mg/L air

Exp. duration:

7 h

Mortality:

no mortality observed

Clinical signs:

other: During exposure: ragged breathing, wiping of snout, nasal secretion Directly after exposure: accelerated breathing, crusted noses in some animals or nasal secretion All signs had ceased by day 1 after exposure.

Gross pathology:

no abnormalities detected

Interpretation of results:

study cannot be used for classification

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Species:

rat

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

secondary source without any other data

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance does not meet the criteria for classification and labelling for acute oral toxicity under Regulation (EC) No. 1272/2008.