1-[1,3-bis(hydroxymethyl)-2,5-dioxoimidazolidin-4-yl]-1,3-bis(hydroxymethyl)urea

Endpoint summary

Description of key information

Acute oral toxicity to rodents is low: LD50 >2000 mg/kg.
Acute dermal toxicity to rabbits is low: LD50 >2000 mg/kg.

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:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well reported study performed under GLP and following a standard test method.

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Males 257-297g, females 226-255g bodyweight.

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

distilled

Details on oral exposure:

Animals fasted for 16-20h pre-dose.

Doses:

2000 mg/kg only.

No. of animals per sex per dose:

5 males, 5 females

Details on study design:

Rats observed 1, 2 and 4h post dose (Day 0), then daily for 14 days (with mortality checks twice daily).

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 reported as approximately 2000 mg/kg: 2/5 males and 2/5 females died following administration of this dose.

Mortality:

1 male, 2 females died on the day of dosing. 1 male died the following day.

Clinical signs:

other: Diarrhoea and anogenital soiling were seen in all treated animals.

Gross pathology:

Abnormalities of the liver, adrenals and gastrointestinal tract were seen in decedents.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the observed mortality following oral administration of 2000 mg/kg, the acute LD50 is concluded to be close to, but above, 2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

All studies used to conclude the acute oral LD50 value are considered reliable (Klimisch scores 1 or 2).

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well reported study performed under GLP and using a standard test method.

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

Bodyweights 2.1-3.0 kg males, 2.3-2.4 kg females pre-test.

Type of coverage:

occlusive

Vehicle:

water

Remarks:

patch and test material moistened with distilled water (0.2 ml)

Details on dermal exposure:

Moistened test substance applied to previously clipped test sites (dorsal skin, ca. 10% of body surface area) then covered with gauze, plastic sheet and tape.

Duration of exposure:

24h

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 males, 5 females

Control animals:

not required

Details on study design:

Dressings removed after 24h and test sites subsequently washed with distilled water. Test sites observed 1, 7 and 14 days post-treatment. Animals observed 1, 2 and 4h post-treatment, then daily up to 14 days.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No deaths occurred and no significant evidence of systemic toxicity was observed.

Mortality:

No deaths occurred.

Clinical signs:

other: One day after treatment, 2 females showed minor (grade 1) skin reactions at test sites; in one of these, the reactions persisted to day 7. No clear indications of systemic toxicity was observed (only sporadic observations of reduced faecal production were

Gross pathology:

No abnormal observations were reported at necropsy.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Low dermal toxicity was recorded in this study: acute dermal LD50 in the rabbit >2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The key study employed a standard EPA test method and was performed under GLP (Klimisch 1).

Additional information

In addition to the studies of acute toxicity via oral, inhalation and dermal routes, a study using mice showed relatively low toxicity via intraperitoneal injection (combined sexes LD50 981 mg/kg).

Justification for selection of acute toxicity – oral endpoint
Three studies of acute oral toxicity in the rat are available. Studies of the test substance itself reported LD50 (combined sexes) values of 2570 g/kg and approximately (just above) 2000 mg/kg, with no indication of a sex-related difference in response. A study using an aqueous solution reported LD50 values for males and females which correspond respectively to substance LD50s of 2100 and 1450 mg/kg. A study using mice reported comparable acute oral toxicity in males and females, with a combined sexes LD50 of 3703 mg/kg. Taking a weight of evidence approach, it is concluded that the acute oral LD50 of the substance in rodents is >2000 mg/kg.

Justification for selection of acute toxicity – inhalation endpoint
The 4.5h LC50 value reported in the available study is considered unreliable, due to experimental and reporting deficiencies (but it may suggest relatively low toxicity). Acute inhalation toxicity is assessed by extrapolation from the acute oral toxicity data (using route-to-route conversion calculations).

Justification for selection of acute toxicity – dermal endpoint
LD50 >2000 mg/kg determined in a reliable key study.

Justification for classification or non-classification

Acute toxicity via oral and dermal routes is low and no classification in respect of this is warranted.