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

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Although this study was performed under GLP and following a standard test method, the report has major deficiencies. The test material was an aqueous 50% solution and the report conclusion cites LC50 values for such a solution, but tabulated data suggest exposure concentrations used for LC50 calculation are for active ingredient. Additionally, the reported very high humidity in test chambers could have adversely affected crystallisation of solid material from aerosol, making the gravimetric analysis of test atmospheres unreliable. Finally, the whole-body exposure employed is likely to have incurred intake via ingestion (grooming) and even perhaps dermal contact, since test material was reported on the fur at all test concentrations.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPP 81-3 (Acute inhalation toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

278-928-2

EC Name:

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

Cas Number:

78491-02-8

Molecular formula:

C8H14N4O7

IUPAC Name:

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

Test material form:

other: aqueous 50% solution (clear colourless liquid)

Details on test material:

Germall II, 50% solution (Integra 22), Lot G-363-S

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Bodyweights at start of test: males 204-252g, females 201-237g. Individually caged during exposure.

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

4.5h

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Gravimetric analysis with particle size measurement

Duration of exposure:

4.5 h

Concentrations:

Preliminary test: 5.01 mg/l
Definitive test: 0.53, 1.20, 1.98 mg/l
Concentrations were based on gravimetric measurements of samples taken at the respiration zone and reflect the solid phase or the active ingredient.

No. of animals per sex per dose:

5 males, 5 females

Control animals:

no

Details on study design:

During test exposure, rats were observed every 15 minutes for 1h, then every 30 minutes. Following exposure, rats were examined at least once daily.

Results and discussion

Preliminary study:

Exposure at 5.01 mg/l caused 100% mortality within 4 days.

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LC50

Effect level:

1.35 mg/L air

Based on:

test mat.

95% CL:

1.03 - 1.76

Exp. duration:

4.5 h

Effect levels 2

Sex:

female

Dose descriptor:

LC50

Effect level:

1.25 mg/L air

Based on:

test mat.

95% CL:

1.02 - 1.54

Exp. duration:

4.5 h

Effect levels 3

Sex:

male/female

Dose descriptor:

LC50

Effect level:

1.3 mg/L air

Based on:

test mat.

95% CL:

0.99 - 1.71

Exp. duration:

4.5 h

Mortality:

0.53 mg/l: no mortality
1.20 mg/l: 40% mortality by day 2
1.98 mg/l: 90% mortality by day 3

Clinical signs:

other: 0.53 mg/l: signs included lethargy, hunched posture, irregular respiration during exposure and (hunched posture, irregular respiration) for 2 subsequent days 1.20 mg/l: signs included lethargy, hunched posture, irregular respiration during exposure. Subs

Gross pathology:

Necropsy of decedents revealed distension and discoloration of the gastrointestinal tract plus reddening of the lungs.

Any other information on results incl. tables

Exposure at 0.53 mg/l produced only transient clinical signs: animals recovered by day, gained weight and showed no gross abnormalities at necropsy. 0.53 mg/l (corresponding to 0.27 mg registered substance/l) is therefore considered a 4.5h NOAEC.

Test atmospheres:

- 0.53 +/- 0.05 mg/l, mass median aerodynamic diameter ca. 2.9 microns (ca. 7% <1 micron, 53% <3 microns)

- 1.20 +/- 0.13 mg/l: mass median aerodynamic diameter ca. 2.5 microns (ca. 8% <1 micron, 61% <3 microns)

- 1.98 +/- 0.14 mg/l: mass median aerodynamic diameter ca. 2.4 microns (ca. 7% <1 micron, 66% <3 microns)

- 5.01 +/- 0.24 mg/l: mass median aerodynamic diameter ca. 2.6 microns (ca. 7% <1 micron, 60% <3 microns)

Applicant's summary and conclusion

Interpretation of results:

other: LC50 value unreliable, but suggestive of relatively low toxicity.

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The report conclusion cites LC50 values for the 50%-solution, but tabulated data suggest exposure concentrations used for LC50 calculation are for active ingredient. The reported very high humidity in test chambers could have adversely affected crystallisation of solid material from aerosol, making the gravimetric analysis of test atmospheres unreliable. Further, the whole-body exposure employed is likely to have incurred intake via ingestion (grooming) and even perhaps dermal contact, since test material was reported on the fur at all test concentrations. As a consequence, a reliable inhalation LC50 for the registered substance (active ingredient in the tested solution) cannot be concluded from this study. The LC50 value of 1.3 mg/L for the active ingredient is most likely an oversetimation of the acute toxicity by inhalation.