Registration Dossier

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: Study was conducted according to GLP as well as Guidelines .

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report date:
1989

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Animals were ca. 7-8 weeks of age at start of treatment. Males weighed 202-293g, females weighed 141-216g at start of treatment.

Standard Laboratory Conditions: Air-conditioned with 7.5-15 a i r changes per hour, and hourly monitored environment w i t h the temperature 21 ± 4°C, the relative humidity 50-85% and 12 hours artificial fluorescent light / 12 hours dark.

Accommodation: Group housed, five per sex to a cage, using polycarbonate cages containing purified sawdust as bedding material (Woody Clean supplied by Broekman Institute , Someren, The Netherlands).

Diet: Free access to standard pelleted laboratory animal diet (RMH-B from Hope Farms, Woerden, The Netherlands). Certificates of analysis are retained in the RCC NOTOX archives.

Water: Free access to tap-water. Certificates of analysis are retained in the RCC NOTOX archives.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
4200, 5000, 6200 mg/kg bw
Specific gravity taken to be 0.83 g/ml - volumes administered were 7.47, 6.02 & 5.06 ml/kg body weight (high to low dose group respectively)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Mortality/viability determined at periodic intervals on the day of dosing (day 1) and twice daily thereafter for at least 14 days.

Body weights were measured on test days 1 (pre-administration), 8 and 15.

Symptoms evaluated at periodic intervals on the day of dosing (day 1) and once daily thereafter.

All signs of reaction to treatment were recorded with particular attention paid to changes in the skin, fur, eyes and mucous membranes, as well as to behaviour pattern, tremors, convulsion, salivation, diarrhoea, lethargy, sleep and coma.

Necropsy: All animals were necropsied and descriptions of all macroscopic abnormalities were recorded. All animals surviving to the end of the observation period were sacrificed by carbon dioxide asphyxiation and subjected to necropsy.
Statistics:
The LD-50 values and the associated 95% confidence interval , the slope o f the dose mortality curve were calculated using the Maximum likelihood method (Finney, O.G. Probit Analyses, 3rd Edn., London, Cambridge, University Press, 1971)

Results and discussion

Preliminary study:
In order to establish an appropriate dose range, three groups of animals, each comprising of 1 male and 1 female, received a single oral dose of test substance a t 3445, 2067 or 1038 mg/kg body weight. The rats were then observed for 8 days.

There were no deaths. Major clinical signs seen among the animals were ataxia, lethargy , pallor , rattled respiration , slimy salivation , piloerection , emaciation and bloody nose encrustation. All animals had recovered by day 3 and all animals gained body weight during the study period.
Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
4 904 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
4 947 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 927 mg/kg bw
Based on:
test mat.
Mortality:
The incidence of mortality for the sexes combined, from low- to high-dose group, was 3, 4, and 9.
The incidence of mortality for males was 2, 1, and 5.
The incidence of mortality for males was 1, 3, and 4.
Clinical signs:
Lethargy, absence of reactions, ataxia, piloerection and breathing difficulties were seen among animals from all the groups. Dacryorrhoea was seen among animals dosed at 6200 or 5000 mg/kg bodyweight and pallor and bloody eye or nose encrustation and salivation were also noted among animals dosed at 5000 mg/kg bodyweight.
Body weight:
All surviving animals showed body weight gain during the study period (days 1-15). Males of the low and mid-dose groups gained 64 ± 4.3 g (n=4) and 90 ± 4.4 g (n=3) respectively. Females of the low-, mid-, and high-dose groups gained 63 ± 8.4 g (n=4), 43 ± 2.1 g (n=2), and 47 g (n=1) respectively. [Data mean ± SD.]
Gross pathology:
Abnormalies revealed at necropsy of animals that died during the study, were pallor of or haemorrhages in the glandular stomach and enlargement of or blood in the bladder, among animals dosed at 6200 mg/kg bodyweight, haemorrhages or blood clots in the glandular and/or forestomach and blood clots in the bladder among animals dosed at 5000 mg/kg bodyweight and enlargement of the bladder among animals dosed at 4200 mg/kg bodyweight. Abnormalities revealed at macroscopic postmortem examination of animals killed at termination were white/grayish irregular or thickened areas in the epithelium of the fore-stomach among animals dosed at 6200 or 4200 mg/kg bodyweight.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Estimated oral LD-50 values of 1-methoxy-2, 7-octadiene is 4927 mg/kg in the sexes combined.
4904 mg/kg body weight in males alone and 4947 mg/kg body weight in females alone.