Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Remarks:
This experimental study was performed only for one constituent (2,2'-[ethylenebis(oxymethylene)]bisoxirane, CAS 2224-15-9, EC 218-746-2) of the UVCB substance.
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report Date:
1978

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: modified procedure in "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, Published by the Association of Food and Drug Officials of the U.S. (1959)"
Deviations:
not specified
Principles of method if other than guideline:
- Short description of test conditions: Adult Sprague-dawley rats were fasted for 18 h prior dosing with the test item. Groups of 5 males and 5 females were administered with the test item via gavage at doses of 0.5 - 5.0 mL/kg bw, and thereafter observed for signs of mortality for 14 days.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 207 - 268 g (males); 155 - 207 g (females)
- Fasting period before study: yes, animals were fasted 18 h prior to dosing.
- Diet: ad libitum
- Water: ad libitum

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 25% (v/v)
Doses:
0.5, 1.5, 1.75, 2.00, 2.30, 2.50, 2.75, 3.25 and 5.00 mL/kg bw
equivalent to: 0.564, 1692, 1974, 2256, 2594, 2800, 3102, 3666 and 5640 mg/kg bw (calculated based on the density of 1.1280 g/mL)
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: Animals were daily observed for signs of mortality. The body weight was recorded prior to dosing of all animals and 14 days after treatment of the survivors.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Statistics:
LD50 values were determined according to the method of Miller and Tainter (Proc. Soc. Biol. Med. 57, 261, 1944).

Results and discussion

Preliminary study:
2 animals per group were exposed to the test substance at doses of 1.0, 2.5, 5.0, 10.0 and 15.0 mL/kg bw, equivalent to: 1128, 2820, 5640, 11280 and 16920 mg/kg bw (calculated based on the density of 1.1280 g/mL). At a dose level of 2820 mg/kg bw and higher all animals died one day at the latest after treatment. At the dose level of 1128 mg/kg bw all animals survived up to the end of the observation period of 7 days.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 800 mg/kg bw
Based on:
test mat.
Remarks:
LD50 was reported in the study as 2.5 mL/kg bw and was converted using a density value of 1.128 g/mL.
Mortality:
0.564 mg/kg bw: No deaths occurred.
1692 mg/kg bw: No deaths occurred.
1974 mg/kg bw: No deaths occurred.
2256 mg/kg bw: No deaths occurred.
2594 mg/kg bw: 2/10 animals died on the day of treatment, 4/10 animals died on day 1, 1/10 animals died on day 4 and 5, respectively (sex not specified).
2800 mg/kg bw: 3/10 animals died on day 1, 1/10 animals died on day 5 and 6, respectively (sex not specified).
3102 mg/kg bw: 8/10 animals died on day 1 and 2/10 animals died on day 2 (sex not specified).
3666 mg/kg bw: 3/10 animals died on the day of treatment, 4/10 animals died on day 1, 1/10 animals died on day 2 and 4, respectively (sex not specified).
5640 mg/kg bw: 4/10 animals died on the day of treatment, 3/10 animals died on day 1, 2/10 animals died on day 3 and 1/10 animals died on day 5 (sex not specified).
Clinical signs:
0.564 mg/kg bw: Decreased activity (not further specified)
1692 mg/kg bw: Decreased activity, ataxia (not further specified)
1974 mg/kg bw: Decreased activity, ataxia (not further specified)
2256 mg/kg bw: Decreased activity, ataxia, salivation, urinary incontinence (not further specified)
2594 mg/kg bw: Decreased activity, ataxia, salivation, urinary incontinence, tremor (not further specified)
2800 mL/kg bw: Decreased activity, ataxia, salivation, urinary incontinence, bloody nasal discharge, rales (not further specified)
3102 mg/kg bw: Decreased activity, ataxia, decreased respiration (not further specified)
3666 mg/kg bw: Decreased activity, ataxia, urinary incontinence, bloody nasal discharge, decreased respiration (not further specified)
5640 mg/kg bw: Decreased activity, severe ataxia, urinary incontinence (not further specified)
Body weight:
The body weight was only recorded for the animals that survived up to the end of the observation period (Day 14). Therefore for the animals treated with dose levels from 0.564 to 2256 mg/kg bw no effect on body weight was noted.
Gross pathology:
The following findings were noted for the animals that died (please also refer to "mortality" and "Clinical signs"):
2594 mg/kg bw: Lungs: dark; liver: dark; spleen: dark; kidneys: pale; intestines: contain a bloody substance (not further specified)
2800 mg/kg bw: Lungs: dark; liver: dark; spleen: dark and granular; kidneys: dark and mottled; intestines: contain a bloody substance (not further specified)
3102 mg/kg bw: Lungs: dark and mottled; liver: dark; spleen: dark; kidneys: dark; intestines: contain a bloody substance (not further specified)
3666 mg/kg bw: Lungs: dark and mottled; liver: dark and granular; spleen: dark and granular; kidneys: dark; intestines: contain a bloody substance (not further specified)
5640 mg/kg bw: Lungs: mottled; liver: dark and mottled; spleen: granular; kidneys: dark and mottled; GI tract: red in color; skin: vascularized (not further specified)

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
Conclusions:
CLP: not classified