Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 July 1995 to 26 September 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Guideline-conform study under GLP without deviations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Dicloroviniletere
- Substance type: pure substance
- Physical state: liquid
- Analytical purity: >99%
- Impurities (identity and concentrations): not reported
- Composition of test material, percentage of components: not reported
- Isomers composition: not reported
- Purity test date: not reported
- Lot/batch No.: 18852/3
- Expiration date of the lot/batch: July 1996
- Stability under test conditions: not reported
- Storage condition of test material: no specific requirements.
- Other: The test substance could slowly give HF under storage condition, therefore it was purify before the administration according to the method supplied by the sposor.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Livestock
- Age at study initiation: 7-9 weeks
- Weight at study initiation: Males: 225-250 g, Female: 200-225 g
- Fasting period before study: 16 hours
- Housing: 5 animals/sex/cage in T11 air conditioned room.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: Five days before the start of the test. Animals were observed daily to ascertain their fitness for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +-2
- Humidity (%): 55 +- 10
- Air changes (per hr): about 20/hour filtered on HEPA 99.97%
- Photoperiod (hrs dark / hrs light): 12 / 12 (7 a.m.- 7 p.m.)

IN-LIFE DATES: All animals were killed on day 15 of the study.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: undiluted
- Amount of vehicle (if gavage): The volume of administration was 1.3 ml/kg in order to obtain the dose of 2000 mg/kg the density being 1.533 g/ml.
- Justification for choice of vehicle: not applicable

MAXIMUM DOSE VOLUME APPLIED: 1.3 mL/Kg bw corrisponding to 2000 dose mg/Kg bw
Doses:
2000 mg /Kg bw
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations of clinical signs: at 30 minutes, 2, 4 and 6 hours (4 males) and at 30 minute, 2 and 4 hours (1 male and 5 females) on the first day after the administration (day 1) and then twice a day up to termination of the observation period.
- Body weighing: twice pre-trial (at randomization and on day 1 just before administration) and on days 3, 8 and 14. On day 1 the animals were weighted after 16-hour fasting. Volume of administration was based oh day 1 Body weight.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology examination.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
discriminating dose
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No animals died during the study. The LD50 was not calculated and it was considered higher than 2000mg/kg.
Clinical signs:
Piloerection was the only clinical sign sporadically observed in all animals only during on the third day of the study.
Body weight:
Decrease in body weight was observed at the day 3 weighing.
Body weigh gain returned to normal at the subsequent weighings.
Gross pathology:
At the autopsy carried out at the end of the observation period no appreciable macroscopic findings were evident in any treated rat.
Other findings:
none.

Any other information on results incl. tables

CLINICAL SIGNS OF INCIDENCE

(No. of animals affected)

CAGE: 1M                                                           
 DAY   1          2    3    4    5    6    7    8    9    10    11    12    13    14   
 TIME   30m 2h 4h 6h M A M A M A M A M A M A M A M A M A M A M A M A M A
Number of animals
showing clinical signs
No clinical signs 5 5 5 5 5 5     5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5
Piloerection             5 5                                          

CAGE: 2F          
 DAY   1       2    3    4    5    6    7    8    9    10    11    12    13    14         
 TIME   30m 2h 4h M A M A M A M A M A M A M A M A M A M A M A M A M A      
Number of animals
showing clinical signs
No clinical signs 5 5 5 5 5     5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5      
Piloerection           5 5                                                

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 of the test article, when administered to rats as a single dose by oral route, is higher than 2000 mg/kg bw.
Executive summary:

Experimental data from a toxicity study in which Sprague Dawley rats received a single oral administration of the test article at the dosage of 2000 mg/kg bw (5 males and 5 females) are given in this report.

The test method was in accordance with European Economic Community Guidelines B.1 and with OECD guidelines 401 and in compliance with GLP.

The test article was purified according to the method supplied by the Sponsor and then administered undiluted at the volume of 1.3 ml/kg in order to give the dose of 2000 mg/kg being the density 1.5333 g/ml.

All rats were treated after a 16 hours fasting period. The day of treatment was considered day 1 of the study. The animals were weighed twice before treatment (at randomization and on day 1 just before treatment) and on day 3, 8 and 14. They were clinically observed for 14 days following the treatment. On day 15 all rats were killed and submitted to a thorough autopsy.

No animals died during the study. The LD50 was higher than 2000 mg/kg bw.

There were no clinical signs or behavioral alterations during the post-treatment observation period (except for piloerection which was noted during the third day of the study).

Decrease in body weight was observed only at the day 3 weighing.

At the autopsy carried out at the end of the observation period no appreciable macroscopic findings were evident in any treated rat.