Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1968
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented study which meets basic scientific principles

Data source

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

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
(adopted 1987)
Deviations:
yes
Remarks:
; only 7 days observation period (14 days recommended by OECD guideline); body weights of the animals were not recorded at test ending.
Principles of method if other than guideline:
BASF test, in principle comparable to the OECD Guideline 401 (1987)
GLP compliance:
no
Remarks:
GLP was not compulsory at the time the study was conducted
Test type:
standard acute method
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:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
Designation: US-Ratten
Source: no data
Age at test initiation: no data
Bodyweight range at test initiation: males 134-198 g, females 150-182g

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Traganth
Details on oral exposure:
The test substance was given to the animals as aqueous emulsion using Traganth as vehicle at following concentrations: 2%, 20% and 30%.
The 30% test solution served for preparation of the 3.2, 4.0, 5.0 and 6.4 ml/kg bw dose levels;
The 20% test solution served for preparation of the 1.6 ml/kg bw dose level;
The 2% test solution served for the preparation of the 0.2 ml/kg bw dose level.
The application volume was as follows:
- 21.3 ml/kg bw for the 6.4 ml/kg bw group,
- 16.6 ml/kg bw for the 5.0 ml/kg bw group,
- 13.3 ml/kg bw for the 4.0 ml/kg bw group,
- 10.6 ml/kg bw for the 3.2 ml/kg bw group,
- 8.0 ml/kg bw for the 1.6 ml/kg bw group,
- 10.0 ml/kg bw for the 0.2 ml/kg bw group.
Doses:
Original doses:
0.2, 1.6, 3.2, 4.0, 5.0 and 6.4 ml/kg bw
Doses in mg/kg bw (according to a density of 1.005g/cm3):
201, 1608, 3216, 4020, 5025, 6432 mg/kg bw
No. of animals per sex per dose:
10 animals/sex/group were used
Control animals:
no
Details on study design:
The animals received a single application of the test material by gavage. Thereafter, they were observed over a period of 7 day for mortality and clinical symptoms of toxicity. At the end of the observation period, the animals were sacrificed for the purpose of necropsy.
Statistics:
no data

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 523 mg/kg bw
Remarks on result:
other: (original reported value: 4.5ml/kg bw)
Mortality:
Mortalities were as follows:
201 mg/kg bw: none (0/20)
1608 mg/kg bw: none (0/20)
3216 mg/kg bw: none (0/20)
4020 mg/kg bw: 5/20 (4 females and 1 male)
5025 mg/kg bw: 17/20 (10 females and 7 males)
6432 mg/kg bw: 20/20

Time point of death:
In the 6432 mg/kg bw group, all mortalities occurred within the first 24 hours following treatment;
In the 5000 and 4000 mg/kg bw groups, all mortalities occurred within 48 hours following treatment.
Clinical signs:
At 201 and 1608 mg/kg bw: piloerection, labored respiration, chewing, and in some cases, slightly staggering gait were reported; these signs disappeared within 1 to 2 days.
At 3216 mg/kg bw: severe staggering gait, apathy, side and prone position, and dyspnea were reported; these effects disappeared within 3 days.
At 4020 and 5025 mg/kg bw: severe staggering gait, dyspnea, chewing, aqueous oral secretion, side and prone position, intermittent, barely noticeable respiration and apathy were reported; the survivors recovered from day 3 post-treatment and were free of symptoms after the fourth following treatment.
At 6432 mg/kg bw: immediately following treatment, the animals showed severe staggering gait, followed by total apathy, dyspnea, and side and prone position; None of them survived day 1 post treatment.
Remark: at the higher doses, females reacted more sensitively than males.
Body weight:
Final body weights were not recorded.
Gross pathology:
Necropsy of those animals that survived and were sacrificed at the end of the observation period of 7 days revealed no abnormalities.
Necropsy of the rats that died mainly revealed bloody lungs partly with edema, as well as serous contents in the thorax. In some cases, liver congestion with questionable fatty degeneration and thightly filled urinary bladder were seen.

Applicant's summary and conclusion