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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
repeated dose toxicity: oral, other
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report date:
2013

Materials and methods

Test guideline
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
Version / remarks:
Adopted: 22 March 1996
GLP compliance:
yes
Remarks:
Japan Existing Chemical Data Base: All the tests reported were performed in accordance with the chemicals GLP under the Law concerning Examination and Regulation of Manufacture, etc. of Chemical Substances and also meet the requirements of the OECD GLP.
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2,2'-[ethylenebis(oxymethylene)]bisoxirane
EC Number:
218-746-2
EC Name:
2,2'-[ethylenebis(oxymethylene)]bisoxirane
Cas Number:
2224-15-9
Molecular formula:
C8H14O4
IUPAC Name:
2,2'-[ethylenebis(oxymethylene)]bisoxirane
Details on test material:
weight per epoxy: 115

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
water for injection
Duration of treatment / exposure:
28 d
Frequency of treatment:
1x / day
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (nominal)
Dose / conc.:
12.5 mg/kg bw/day (nominal)
Dose / conc.:
50 mg/kg bw/day (nominal)
Dose / conc.:
200 mg/kg bw/day (nominal)
No. of animals per sex per dose:
main groups: 6 males and 5 females for control, 12.5, 50 and 200 mg/kg
recovery groups: 6 males for control, 12.5, 50 and 200 mg/kg and 5 females for control and 200 mg/kg
Control animals:
yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes

DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: Yes

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Not specified

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: on termination of administration period and on termination of recovery period
- How many animals: all animals (6 males / dose and 5 females / dose ; recovery groups: 6 males / dose and 5 females / dose)
- Parameters examined: RBC, hemoglobin, hematocrit, MCV, MCH, MCHC, platelet, reticulocyte, PT, APTT, fibrinogen, WBC, differential leukocyte (lymphocyte, neutrophil, eosinophil, basophil, monocyte)

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: on termination of administration period and on termination of recovery period
- How many animals: all animals (6 males / dose and 5 females / dose ; recovery groups: 6 males / dose and 5 females / dose)
- Parameters examined: AST, ALT, ALP, gamma-GT, total protein, albumin, A/G, total bilirubin, urea nitrogen, creatinine, glucose, total cholesterol, triglyceride, Na, K, Cl, Ca, inorganic phosphorus , T3, T4, TSH

URINALYSIS: Yes
- Time schedule for collection of urine: on termination of administration period and on termination of recovery period
- Parameters examined: color, pH, protein, glucose, ketone body, bilirubin, occult blood, urobilinogen, urinary sediments (epithelial cells, erythrocytes, leukocytes, casts, crystals)

NEUROBEHAVIOURAL EXAMINATION: Yes
- Dose groups that were examined: 0, 12.5, 50, 200 mg/kg
- Battery of functions tested: sensory activity, grip strength, motor activity

IMMUNOLOGY: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes

HISTOPATHOLOGY: Yes

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Salivation at 200 mg/kg post-administration in males and females. Probably due to irritating properties of the test substance.
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Lower body weight at 50 and 200 mg/kg in males at the end of the administration period
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Lower food consumption at 200 mg/kg in males at days 5, 9 and 12 and in females at days 5 and 9.
Food efficiency:
not specified
Ophthalmological findings:
not examined
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
No effects observed in males at termination of administration period.
females at 200 mg/kg at termination of administration period: platelet (increase), reticulocyte (increase), PT (increase), lymphocyte (increase), neutrophil (decrease)
females at 50 mg/kg at termination of administration period: platelet (increase), lymphocyte (increase), neutrophil (decrease)
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
No effects observed in females at termination of administration period.
Treatment-related effects observed in males at 200 mg/kg at termination of administration period: triglyceride (decrease) => not statistically significantly different after recovery period
Treatment-related effects observed in males at 50 mg/kg at termination of administration period: triglyceride (decrease) => not statistically significantly different after recovery period
Urinalysis findings:
no effects observed
Description (incidence and severity):
No effects observed in females at termination of administration period.
Behaviour (functional findings):
no effects observed
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, non-treatment-related
Description (incidence and severity):
No effects observed in females at 200 mg/kg at termination of administration period.
Effects observed in males at 200 mg/kg at termination of administration period: liver absolute (decrease), testes relative (increase) => not observed after recovery period
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Males and females at 50 and 200 mg/kg: stomach ulcer, glandular stomach, chronic => due to irritating properties test substance

Effect levels

open allclose all
Key result
Dose descriptor:
NOAEL
Effect level:
12.5 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
clinical biochemistry
Key result
Dose descriptor:
NOAEL
Effect level:
12.5 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
haematology

Target system / organ toxicity

open allclose all
Critical effects observed:
yes
Lowest effective dose / conc.:
50 mg/kg bw/day (actual dose received)
System:
haematopoietic
Organ:
blood
Treatment related:
yes
Critical effects observed:
yes
Lowest effective dose / conc.:
50 mg/kg bw/day (actual dose received)
System:
hepatobiliary
Organ:
blood
Treatment related:
yes
Dose response relationship:
no

Applicant's summary and conclusion

Conclusions:
The following treatment-related effects were likely due to the irritating properties of the substance: salivation at 200 mg/kg and stomach ulcher at 50 and 200 mg/kg.
Systemic effects observed in males are the decrease in triglycerides and lower body weight at 50 and 200 mg/kg. The toxicological relevance of the decrease in triglycerides is not clear: this effect was not observed in females, no dose-response was present and the triglyceride levels were normal after the recovery period.
In females an increase in platelets, lymphocytes and neutrophils is observed at 50 and 200 mg/kg. This could also be related to the observed stomach ulcer at these dose levels.