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Diss Factsheets

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:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report date:
1993

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
February 24, 1987
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
September 1984
GLP compliance:
yes
Test type:
acute toxic class method

Test material

Constituent 1
Chemical structure
Reference substance name:
1,1'-[methylenebis(sulphonyl)]diethylene
EC Number:
221-909-0
EC Name:
1,1'-[methylenebis(sulphonyl)]diethylene
Cas Number:
3278-22-6
Molecular formula:
C5H8O4S2
IUPAC Name:
(ethenesulfonyl)methanesulfonylethene
Test material form:
solid: particulate/powder

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Outbred, SPF quality
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: BRL Ltd., Basel, Switzerland
- Age at study initiation: Approx. 9-11 weeks
- Weight at study initiation: males: 227-308g / females: 165-204g
- Fasting period before study:
- Housing: Group housed, five per sex to a cage, using labelled polycarbonate cages containing purified sawdust as bedding material (Woody SPF supplied by B.M.I., Someren, The Netherlands). Certificates of analysis were examined and then retained in the RCC NOTOX archives.
- Diet (e.g. ad libitum): Free access to standard pelleted laboratory animal diet (Klibe 343 from Klingentalmühle AG, Kaiseraugst, Switzerland). Certificates of analysis were examined and then retained in the RCC NOTOX archives.
- Water (e.g. ad libitum): Free access to tap-water. Certificates of analysis were examined and then retained in the RCC NOTOX archives.
- Acclimation period: at least 5 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C
- Humidity (%): 55%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
1% aq.
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20 / 65 / 200 mg/kg body weight
- Amount of vehicle (if gavage): 10 ml/kg body weight

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg body weight

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Initially one group of animas consisting of 5 males and 5 females were dosed with V190110 in 1% aq. carboxymethyl cellulose at a dose level of 200 mg/kg body weight. Due to the fact that all animals died, two further groups were added for the full study and animals dosed at 65 or 20 mg/kg body weight.
Doses:
Group 1: 20 mg/kg body weight
Group 2: 65 mg/kg body weight
Group 3: 200 mg/kg body weight
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Day 1, 8 and 15 and at death
- Necropsy of survivors performed: yes
- Other examinations performed:
clinical signs: at periodic intervals on the day of dosing (day 1) and once daily thereafter. The time of onset, degree and duration were recorded.
body weight: days 1 (pre-administration), 8 and 15 and at death (if found dead after 1 day).
Statistics:
The LD50 values and the associated 95% confidence interval, the slope of the dose mortality curve were calculated using Probit Analysis (SAS Technical Report: P-179, Additional SAS/STAT Procedures, Release 6.03, Chapter 4, the Probit Procedure).

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
60 mg/kg bw
Sex:
male
Dose descriptor:
LD50
Effect level:
63 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
58 mg/kg bw
Mortality:
The following mortality rates were observed:
Dose level Males Females Combined
20 mg/kg 0/5 0/5 0/10
65 mg/kg 3/5 4/5 7/10
200 mg/kg 5/5 5/5 10/10

All deaths occurred within 24 hours of dosing.
Clinical signs:
Clinical signs observed during the study period in each dose group were as follows:
20 mg/kg: No clinical signs
65 mg/kg: Lethargy, ventro-lateral recumbency, hunched posture, rough coat.
200 mg/kg: Lethargy, ventro-lateral recumbency, uncoordinated movements, rough coat.

Body weight:
The three surviving animals dosed at 65 mg/kg body weight had recovered by day 7.

The body weight gan shown by the majority of surviving animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. Four females dosed at 20 mg/kg body weight showed lower than expected body weight gain over the second week.
Gross pathology:
Macroscopic post mortem examination of the animals that died during the study revealed the following abnormalities:

65 mg/kg: enlarged stomach, haemorrhages in glandular stomach, dark red discolouration in glandular stomach, duodenum and jejunum, watery contents in abdominal cavity
200 mg/kg: enlarged stomach, dark red discoloration in glandular stomach, pelvic dilation in right kidney.

Renal pelvic dilation is commonly noted among animals of this age and strain and therefore considered not treatment related.
Macroscopic post mortem examination of the surviving animals at termination did not reveal any abnormalities.

Applicant's summary and conclusion

Interpretation of results:
Category 2 based on GHS criteria
Conclusions:
Due to the mortality distribution, only estimated oral LD50 values of V190110 could be obtained for the sexes combined, males alone and females alone. These were 60 mg/kg body weight for the sexes combined, 63 mg/kg body weight for the males alone and 58 mg/kg body weight for females alone.

According to the EEC criteria for classification and labelling requirements for dangerous substances and preparations (EEC Directive 91/325/EEC, Ammendment to Annex VI of the EEC Directive 67/548/EEC), V190110 should be classified as toxic(Acute toxicity Category 3).