Registration Dossier

Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
experimental study
Adequacy of study:
other information
Study period:
1968
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1968

Materials and methods

Test guideline
Qualifier:
no guideline available
GLP compliance:
no
Remarks:
; GLP was not compulsory at the time the study was conducted
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
1,3,5-Trioxan
Purity: 99.99%

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male/female
Details on test animals and environmental conditions:
Designation: Kisslegg mice
Source: no data
Age at test initiation: no data
Bodyweight range at test initiation: males, 31 - 42 g, females, 19 - 33 g

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
other: Traganth
Details on exposure:
- Before administration, the test substance was finely pulverised and an aqueous solution of 2% and 16% was prepared in Traganth.
- The 2% solution was employed for the preparation of the 200 mg/kg bw dose;
- The 16% suspension was used for the preparation of the 1600 mg/kg bw, the 2000 mg/kg bw and the 2500 mg/kg bw doses;
- Suspensions over 16% were not applicable because the application syringe was clogged;
- Application volume for the doses 200 mg/kg bw and 1600 mg/kg bw was 10 ml/kg bw;
- Application volume for the dose 2000 mg/kg bw was 12.5 ml/kg bw;
- Application volume for the dose 2500 mg/kg bw was 15.6 ml/kg bw.
Doses:
200, 1600, 2000 and 2500 mg/kg bw
No. of animals per sex per dose:
5 animals/sex/dose
Control animals:
no
Details on study design:
A single dose of the test substance was injected into the peritoneal cavity of each animal;
The animals from the 200 and 1600 mg/kg bw dose groups were observed for a period of 7 days while the animals administered the doses 2000 and 2500 mg/kg bw were under observation for 14 days;
Animals that died during the observation period were necropsied. At the end of the observation period, surviving animals were sacrificed and subjected to necropsy.
Statistics:
No data

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 800 mg/kg bw
Remarks on result:
other: LD 50 after 14 days
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 300 mg/kg bw
Remarks on result:
other: LD 50 after 7 days
Mortality:
2500 mg/kg bw: mortality was 7/10 animals after 7 days which reached 8/10 after 14 days
2000 mg/kg bw: mortality was 3/10 animals after 7 days which reached 9/10 after 14 days
1600 mg/kg bw: mortality was 2/10 animals after 7 days
200 mg/kg bw: No mortality was observed.
Clinical signs:
2000 and 2500 mg/kg bw:
Symptoms observed immediately after application included weak jumping convulsions, accelerated respiration, closed eyes, impaired movement of the rear limbs, high stepping gait. The symptoms lasted the entire day after application.
One day after application symptoms included prone position, apathy, sticky eyes and unkempt fur.
On day 7 after application, the surviving animals began recovering. From day 9 to day 14, no more symptoms were seen.

200 and 1600 mg/kg bw:
Symptoms observed immediately after application of the test substance included irregular respiration and high stepping gait with lagging hind limbs.
On day 2 after application, symptoms included unkempt fur, apathy, closed eyes, intermittent respiration and prone position.
After 5 days, the surviving animals demonstrated no more symptoms.
Body weight:
No data
Gross pathology:
Results for animals that died during the observation period:
Granular substance incorporations were found between the intestinal loops of 1 female treated with 2500 mg/kg bw dose. Similar incorporations were also seen at 2000 mg/kg bw (2 males). Intraabdominal adhesions were observed in 3 animals treated with 2500 mg/kg bw (both sexes) as well as in 7 animals treated with 2000 mg/kg bw (both sexes).
Of the 2 animals that died in the 1600 mg/kg bw group, putrefaction was observed in 1 female. No documentation was available for the second animal.

Results for animals that were sacrificed:
In the 2500 mg/kg bw group, necropsy of the sacrificed animals (1 male and 1 female) revealed compact intraabdominal adhesions in both animals.
No necropsy documentation was available for the only surviving animal in the 2000 mg/kg bw group.
Intraabdominale adhesions were observed in the surviving animals of the 200 mg/kg bw (5 males, 5 females) and 1600 mg/kg bw (4 males, 4 females) groups.

Any other information on results incl. tables

LD50 for i.p. (mice of both sexes): 1800 mg/kg bw

Applicant's summary and conclusion