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Diss Factsheets

Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study: OECD Guideline 401 (Acute Oral Toxicity)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report date:
1980

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Oxydiethylene bis(chloroformate)
EC Number:
203-430-9
EC Name:
Oxydiethylene bis(chloroformate)
Cas Number:
106-75-2
Molecular formula:
C6H8Cl2O5
IUPAC Name:
oxydiethane-2,1-diyl dichlorocarbonate
Details on test material:
- Name of test material (as cited in study report): diethylenglykol bis chlorformiat (diglycol bis chloroformate)
Degree of purity not reported.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hagemann + Wiga
- Weight at study initiation: 200g (m); 180g (f).
- Fasting period before study: overnight, 15 - 20 h before treatment

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2.9, 6.3, 20, 29.4,43, 63.2 %.

MAXIMUM DOSE VOLUME APPLIED: 5 ml/kg
Doses:
147, 316, 1000, 1470, 2150, 3160 mg/kg bw
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: Weighing was at the begining of the study and after 3, 7, and 13 days after treatment. Observations wer severaltimes on the day of application and atleast daily thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Probit analysis

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 650 mg/kg bw
95% CL:
1 290 - 2 052
Mortality:
Deaths occurred within 2 days after dosing
Clinical signs:
No symptoms were noted in the animal groups at 147 and 316 mg/kg bw.
In animals at 1000 - 3160 mg/kg bw signs of toxicity included apathy, dyspnea, restlessness, staggering, tremor, ruffled fur, salivation, and poor
general state.
Body weight:
Body weight gain was unaffected in male and female rats at 147 and 316 mg/kg bw. In all groups at 1000 - 3160 mg/kg bw body weights had decreased at 2-4 days after treatment. Thereafter surviving animals gained weight but without reaching the level of the low dose animals until the end of the 14-d observation period.
Gross pathology:
Animals that died: heart: right side dilatation; stomach: bleeding ulcerations (gastric corrosion); lung: distended; intestine: red mucosa, diarrheic
contents, some cases of necrotic mucosa; kidneys: tubular necrosis in one animal.
Sacrificed animals: No findings in animals at 31.6 - 316 mg/kg bw. In animals at 1000 - 3160 mg/kg bw findings in stomach: wall of forestomach
thickened; diverticle formation; gastric mucosa crinkled.

Any other information on results incl. tables

Mortality after 14 days:

                  --------------------------------

                   Dose        males       females

                  (mg/kg)          (dead/exposed)

                  --------------------------------

                   147          0/5         0/5

                   316          0/5         0/5

                  1000          0/5         1/5

                  1470          1/5         3/5

                  2150          3/5         5/5

                  3160          4/5         5/5

                  --------------------------------

Deaths occurred within 2 days after dosing.

The calculated LD50 was 2103 mg/kg bw for male and 1297 mg/kg bw for female rats. The combined LD50 value was 1646 mg/kg bw.

Symptoms:

No symptoms were noted in the animal groups at 147 and 316 mg/kg bw.

In animals at 1000 - 3160 mg/kg bw signs of toxicity included apathy, dyspnea, restlessness, staggering, tremor, ruffled fur, salivation, and poor general state.

Body weight gain was unaffected in male and female rats at 147 and 316 mg/kg bw. In all groups at 1000 - 3160 mg/kg bw body

weights had decreased at 2-4 days after treatment. Thereafter surviving animals gained weight but without reaching the level of the low dose animals until the end of the 14-d observation period.

Pathology:

Animals that died:  heart: right side dilatation; stomach: bleeding ulcerations  (gastric corrosion); lung: distended; intestine: red mucosa, diarrheic contents, some cases of necrotic mucosa; kidneys: tubular necrosis in one animal.

Sacrificed animals: No findings in animals at 31.6 - 316 mg/kg bw. In animals at 1000 - 3160 mg/kg bw findings in stomach: wall of forestomach thickened; diverticle formation; gastric  mucosa crinkled.

Applicant's summary and conclusion