Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1993-04-11 to 1983-04-27
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Cyclooctene of Hüls AG; Purity: 92.7 %

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ORGANISMS: 
- Strain: Bor: WISW (SPF TNO)
- Source: F. Winkelmann, Borchen (Germany)
- Weight at study initiation: males mean 269 g, females mean 146 g
- Fasting period before study: 16 hours
- Diet: Sniff R 10 complete feed for rats, ad libitum
- Water: ad libitum
- Acclimation period: 4 - 8 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 °C +/- 1 °C
- Humidity (%): 60 % +/- 5%
- Air changes (per hr): 15 times/hour
- Photoperiod (hrs dark / hrs light): 12-hour light/dark rythm

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
paraffin oil
Details on oral exposure:
ADMINISTRATION: 
- Doses per time period: single dose (gavage)
- Volume administered or concentration: 10 ml/kg bw
- Post dose observation period: 14 days
- Controls: no
Doses:
3160; 3980; 5010; 6310 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
EXAMINATIONS:
- Body weights: before, and 1, 7, 14 days post dosing
- Clinical signs and mortality: within 6 hours after dosing, thereafter  daily
- Necropsy: 2 males and 2 females per dose (macroscopic), no further  details
Statistics:
LD50 is determined according to Litchfield and Wilcoxon with 95% confidence limits

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 550 mg/kg bw
Mortality:
- Number of deaths at each dose:    
3160 mg/kg bw: no deaths   
3980 mg/kg bw: 3 males, 2 females dead within 96 hours   
5010 mg/kg bw: 4 males, 3 females dead within 77 hours   
6310 mg/kg bw: 5 males, 4 females dead within 96 hours   
LD50 = 4550 (4099-5051) mg/kg bw
Clinical signs:
CLINICAL SIGNS: The signs of toxicity observed about 90 minutes after  application were ruffled fur, ataxia, prone position, crouched posture,  
staggering gait, agitation, spasms, tremor and sedation. With the animals  surviving the treatment, the findings had disappeared after nine days at  
the latest. 
Body weight:
Body weight gain was not affected.
Gross pathology:
NECROPSY FINDINGS: Dissection post mortem revealed redness of the  gastro-intestinal mucosa and a deep-red or grey discoloration of the  lungs.
Among the animals surviving the treatment, at the end of the  period of observation 2 animals from the 3980 mg/kg bw dose group showed  
erythema of the small intestinal mucosa and fusion of organs in the  abdominal cavity, and one animal of the highest dose group showed fluid  
accumulation in the fallopian tube. In all other cases, dissection  revealed no organ findings.

Any other information on results incl. tables

no further information

Applicant's summary and conclusion

Conclusions:
In an acute oral toxicity study, groups of fasted rats, (5/sex/dose) were given a single oral dose (gavage) of Cyclooctene (10.0 mL/kg bw dilution in paraffine) and were observed for 14 days. Oral LD50 was 4550 mg/kg bw.
Executive summary:

In an acute oral toxicity study, groups of fasted rats, (5/sex/dose) were given a single oral dose (gavage) of Cyclooctene (10.0 mL/kg bw dilution in paraffine) and were observed for 14 days. Oral LD50 was 4550 mg/kg bw. The signs of toxicity observed about 90 minutes after application were ruffled fur, ataxia, prone position, crouched posture, staggering gait, agitation, spasms, tremor and sedation. With the animals surviving the treatment, the findings had disappeared after nine days at the latest. Dissection post mortem revealed redness of the gastro-intestinal mucosa and a deep-red or grey discoloration of the lungs.

Among the animals surviving the treatment, at the end of the period of observation 2 animals from the 3980 mg/kg bw dose group showed erythema of the small intestinal mucosa and fusion of organs in the abdominal cavity, and one animal of the highest dose group showed fluid accumulation in the fallopian tube. In all other cases, dissection revealed no organ findings