Registration Dossier

Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
experimental study
Adequacy of study:
other information
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
Report Date:
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:
Butandiolformal (1,3-Dioxacycloheptane)
Purity 99.99%
Physical state: liquid

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: male 30-47g, female 26-40g

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
other: Traganth
Details on exposure:
The test substance was offered to the animals as aqueous emulsion using Traganth as vehicle at following concentrations: 2% , 4%, 8%, 10% and 20%.
The 20% test solution served for preparation of the 1.6 and 3.2 ml/kg bw dose levels, the application volume was 10 ml/kg bw;
The 10% test solution served for preparation of the 1.25 ml/kg bw dose level, the application volume was 12.5 ml/kg bw;
The 8% test solution served for the preparation of the 0.8 ml/kg bw dose level, the application volume was 10 ml/kg bw;
The 4% test solution served for the preparation of the 0.4 ml/kg bw dose level, the application volume was 10 ml/kg bw;
The 2% test solution served for the preparation of the 0.2 ml/kg bw dose level, the application volume was 10 ml/kg bw.
Doses:
200, 400, 800, 1250, 1600 and 2000 mg/kg bw
No. of animals per sex per dose:
2000, 1600, 400 and 200 mg/kg bw: 5 animals/sex/dose were used;
1250 and 800 mg/kg bw: 10 animals/sex/dose were used;
Control animals:
no
Details on study design:
A single dose of the test substance was injected in to the peritoneal cavity of the animals. The animals from the 200 to 1250 mg/kg bw dose groups were observed for a period of 7 days while the animals administered the doses 1600 and 2000 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 levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 500 mg/kg bw
Remarks on result:
other: (after14 days)
Mortality:
2000 mg/kg bw: mortality was 10/10 animals after 7 days, first cases of death occurred within 24 hours following injection;
1600 mg/kg bw: mortality was 7/10 animals after 7 days and reached 9/10 after 14, first cases of death occurred within 24 hours following injection;
1250 mg/kg bw: mortality was 0/20;
800 mg/kg bw: 2/20 animals died between 2 and 7 days following injection;
400 mg/kg bw: mortality was 0/10;
200 mg/kg bw: mortality was 0/10.
Clinical signs:
2000 and 1600 mg/kg bw:
Symptoms observed immediately after application included staggering, jumping convulsions, pain noise, streaking gait (hind limbs). After 2 minutes, side and prone position, dyspnea, partly apathy and partly narcotic state were observed. On the following days, prone position, labored respiration, scrubby fur and clotted eyes were observed. Except for one mice of the 1600 mg/kg bw group, all animals died; the surviving mice recovered slowly, and complete recovery was seen on day 12 post-exposure.

1250 to 200 mg/kg bw:
In these groups, symptoms observed immediately after application included staggering, jumping convulsions, pain noise and labored respiration. On the following days, accelerated respiration and scrubby fur were observed. The surviving animals recovered within 2 to 4 days following injection.
Body weight:
No data on terminal body weights were available.
Gross pathology:
Nearly all animals that died showed more or less firm intraabdominal adhesions; in three cases, sections of the small intestine partly showed vascular injection; in one case, the gastrointestinal tract showed bloody contents.
All animals that were sacrificed at the end of the observation period showed slight to firm adhesions (between liver and stomach, intraabdominal or in the liver).

Applicant's summary and conclusion