Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1983-04-18 to 1983-05-04
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:
1,5-cyclooctadiene of Hüls AG; Purity 99.5 %

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 140 g, females mean 119 g
- Controls: no
- Fasting period before study: 16 hours
- Diet: ad libitum, R10 special diet for rats, SSniff R
- Water: ad libitum, tap water
- Acclimation period: 4 - 8 days
ENVIRONMENTAL CONDITIONS
- Temperature: 20 +/- 1 °C
- Humidity: 60 +/- 5 %
- Photoperiod: 12 hours artificial light, 12 hours dark
- Air changes: 15 per hour

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: no vehicle
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
Doses:
1250; 1580; 1990; 2510 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: 1-5 per sex and dose group (macroscopic), no further details
Statistics:
LD50 is generally determined according to Litchfield and Wilcoxon, reported with 95 % confidence limits.
Means of body weights were calcultated

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 900 mg/kg bw
Mortality:
- Number of deaths at each dose:    
1250 mg/kg bw: no deaths   
1580 mg/kg bw: 0 males, 2 females dead within 33 hours   
1990 mg/kg bw: 2 males, 4 females dead within 120 hours   
2510 mg/kg bw: 4 males, 5 females dead within 96 hours
Clinical signs:
CLINICAL SIGNS: All dosed animals showed toxic symptoms about 45 minutes  after dosing and mostly fading within 6 days after treatment. (one  surviving animal from the highest dose group had a ruffled fur even after  14 days.) Reported symptoms are piloerection, difficult breathing,  impairment of balance, staggering gait, tremor, diuresis, abdominal  position, squatting position and sedation. 
Body weight:
Body weight gain was not affected.
Gross pathology:
NECROPSY FINDINGS: Post mortem sections showed irritated epithelia of the  gastro-intestinal tract and colored spots in the liver. Surviving animals  did not show pathological changes in any tissue after the end of the 14  days observation period. 
Other findings:
no other findings

Applicant's summary and conclusion

Conclusions:
Under the present test conditions, the LD50 value (oral) was determined to be 1900 (1667-2166) mg/kg bw in male and female rats for the test item.
Executive summary:

In a study according to OECD TG 401 (1981) the test item was applied once to 4 dose groups of rats (5 male and 5 female Wistar rats per dose group) in doses of 1250, 1580, 1990, 2510 mg/kg bw undiluted. The observation period was 14 days.

Some mid-dose animals died between 33 and 120 hours, 9 of 10 high dose animals died during 96 hours after oral application of the test item. All dosed animals showed toxic symptoms about 45 minutes after dosing and mostly fading within 6 days  after treatment (one surviving animal from the highest dose group had a ruffled fur even after  14 days). Reported symptoms are piloerection, difficult breathing,  impairment of balance, staggering gait, tremor, diuresis, abdominal  position, squatting position and sedation. Post mortem sections showed irritated epithelia of the gastro-intestinal tract and colored spots in the liver. Surviving animals did not  show pathological changes in any tissue after the end of the 14  days observation period. The LD50 value (oral) was determined to be 1900 (1667-2166) mg/kg bw in rats for the test item.