1,3-bis(hydroxymethyl)-5,5-dimethylimidazolidine-2,4-dione

Endpoint summary

Description of key information

DMDMH readily undergoes hydrolysis to DMH and therefore data is provided for both substances. DMDMH is of low  to moderate acute toxicity and DMH is of low acute toxicity.

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)

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

500, 2320, 3410 and 5000mg/kg

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 890 mg/kg bw

Based on:

test mat.

Mortality:

At 500 mg/kg - 0/10
At 2320 mg/kg - 1/10
At 3410 mg/kg - 8/10
At 5000 mg/kg - 9/10

Clinical signs:

other: Clinical changes noted during the observation period included ataxia, saliva and fecal stains, piloerection, shallow and gasping breathing, slight to severe depression, reddish stains around the eyes and on muzzle and dirty hair coats.

Gross pathology:

The gross necropsy findings in the animals that died were those generally seen in agonal animals. In the animals which survived there were no gross pathological findings.

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LD50 (rat, oral) for Glycoserve II - 2890mg/kg

Executive summary:

The LD50 (rat, oral) for Glycoserve II = 2890mg/kg, equivalent to LD50 (rat; oral) for DMDMH - 1572mg/kg.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 572 mg/kg bw

Quality of whole database:

Sufficient to meet data requirements. The study is Klimisch 1.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

An acute inhalation toxicity study is scientifically unjustified and is not in the interests of animal welfare. Acute studies are available by the oral and dermal routes.

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)

Qualifier:

according to guideline

Guideline:

EPA OPP 81-2 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- % coverage: 10%
- Type of wrap if used: Occlusive

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Water
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.6 ml/kg b.w.

Duration of exposure:

24 hours

Doses:

2000mg/kg/bw of Glycoserve II equivalent to 1052 mg DMDMH/kg/bw

No. of animals per sex per dose:

5/sex/group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Examinations: Gross toxicity including gross evaluation of the skin, fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behaviour pattern

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: None

Gross pathology:

None

Other findings:

Erythema, edema and eschar were present at dose site

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 value for the Glycoserve II is > 2000 mg/kg, equivalent to >1052 mg/kg DMDMH

Executive summary:

The LD50 value for the Glycoserve II (52,6% DMDMH in aqueous solution) is higher than 2000 mg/kg b.w., equivalent value for the active substance (DMDMH) is 1052 mg/kg b.w.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

1 052 mg/kg bw

Quality of whole database:

Sufficient to meet data requirements. The study is Klimisch 1.

Additional information

DMDMH is of low to moderate acute toxicity in mammals. The acute oral LD50 is reported in two different studies as 1572 and 2046 mg/kg respectively while the dermal LD50 is above 1052 mg/kg. Testing by the inhalation route is not scientifically justified.

The hydrolysis product DMH is of low acute toxicity in mammals. The acute oral LD50 is 10000 - 20000 mg/kg and the dermal LD50 is above 20000 mg/kg.

Justification for selection of acute toxicity – oral endpoint
Two studies available on DMDMH. This study is the more reliable and gave the lower dose descriptor.

Justification for selection of acute toxicity – dermal endpoint
Only one study available on DMDMH.

Justification for classification or non-classification

Given the acute oral LD50 values, DMDMH is classified for acute toxicity by the oral route. Following dermal dosing at up to 1052 mg/kg no mortalities or signs of systemic toxicity were seen. Given that signs of toxicity were seen at 1/5th of the LD50 value in the acute oral study, it is concluded that the dermal LD50 lies significantly above 2000 mg/kg and hence classification is not justified for the dermal route.