Butane-1,3-diol

Neurotoxicity

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

Test material information

Constituent 1

Reference substance name:

Butane-1,3-diol

EC Number:

203-529-7

EC Name:

Butane-1,3-diol

Cas Number:

107-88-0

Molecular formula:

C4H10O2

IUPAC Name:

butane-1,3-diol

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 or test system 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 / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
3500
Basis:
actual ingested
test I

Doses / concentrations 2

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).