Registration Dossier

Administrative data

Endpoint:
neurotoxicity: acute oral
Type of information:
experimental study
Adequacy of study:
other information
Study period:
1970
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: publication, insufficient documentation, no validated test procedure

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1970
Report Date:
1970

Materials and methods

Principles of method if other than guideline:
acute neurotoxicity
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): 1,3-butanediol

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River
- Weight at study initiation: 430 g (test I) to 432 g (test II)
- Diet: access from noon to 3 p.m.
- Water: ad libitum
- Acclimation period: one week (test I); "a period of weeks" (test II)

Administration / exposure

Route of administration:
oral: gavage
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
TEST I
- single exposure; five different test-items (1,3-butylene glycol, glycerol, water, sucrose, sham-treated) were tested in parallel, rats received a different treatment each day, five days per week for three weeks and in a different order each week

TEST II
- each dose level was presented to each rat over a five-day period
Frequency of treatment:
TEST I
- on 3 days within 3 weeks

TEST II
- once per day
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
3500
Basis:
actual ingested
test I
Remarks:
Doses / Concentrations:
0, 1750, 3500, 5250, 7000 mg/kg bw
Basis:
actual ingested
test II
No. of animals per sex per dose:
- test I: 8 males per dose
- test II: 8 males per dose
Control animals:
yes, sham-exposed
Details on study design:
TEST II
- corn oil was added to all except the high dose group to produce a constant caloric value across the dose range of 42 kcal/kg
- in the succeeding study run without caloric filler animals were randomly assigned to an "active" and a "restrained" condition; the active group was run exactly as in TEST I; the restrained group was barred from the wheel during the 3 hrs before feeding
- in test II seven additional rats were re-used which had been used in a preliminary sucrose study

The results of TEST I were confirmed in a third test, which was similar to TEST I, but the administered dose was 7000 mg/kg bw/d. Rats had to balance on a rotating dowel instead of measurement of voluntary activity.

Examinations

Neurobehavioural examinations performed and frequency:
- recording of activity in a wheel
- recording the ability to balance on a rotating dowel

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
effects observed, treatment-related
Ophthalmological findings:
not examined
Clinical biochemistry findings:
not examined
Behaviour (functional findings):
effects observed, treatment-related
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Details on results:
TEST I
- rats treated with the test item showed a clearly depressed voluntary activity
- food consumption was reduced, but not statistically significant
- statistically significant reduced water intake during the activity test
- an increased number of falls from the rotating dowel were recorded in the confirmation experiment

- in the confirmation test with the double dose, the test item produced more falls from the rotating dowel than any other substance compared

TEST II
- activity, food and water intake were dose dependently reduced, already at the lowest dose applied

Effect levels

Dose descriptor:
LOAEL
Effect level:
1 750 mg/kg bw/day (actual dose received)
Sex:
male
Basis for effect level:
other: decreased voluntary activity after repeated applications on five consecutive days
Remarks on result:
other:

Any other information on results incl. tables

TEST I

Effects in the second feeding period might be influenced by the effects of the first feeding period.

TEST II

- activity was dose dependently depressed in treated animals, this effect occurred independently if a fat filler was added to the diet or not.

Applicant's summary and conclusion

Conclusions:
Treatment of rats with 1,3-butylene glycol resulted in a reduced voluntary activity of the animals and impaired their ability to balance on a rotating dowel. suggesting that the test item acts as a CNS depressant or strong muscle relaxant.
Executive summary:

Application of 1,3-butylene glycol to rats once a week on three consecutive weeks or five consecutive days in doses >/= 3500 mg/kg bw/d or >/= 1750 mg/kg bw/d, respectively, resulted in a decreased voluntary activity in rats or impaired ability to balance on a rotating dowel. Food uptake and water intake was also depressed (Ayres and Isgrig, 1970).