Butane-1,4-diol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: acceptable, well-documented report which meets basic scientific principles

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Principles of method if other than guideline:

The study was conducted according to an internal BASF method which in principle is comparable to the OECD Guideline 401.

GLP compliance:

no

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

Butane-1,4-diol

EC Number:

203-786-5

EC Name:

Butane-1,4-diol

Cas Number:

110-63-4

Molecular formula:

C4H10O2

IUPAC Name:

butane-1,4-diol

Details on test material:

- Name of test material (as cited in study report): 1.4-Butanediol
- Physical state: colorless liquid
- Analytical purity: 99.3%
- Impurities (identity and concentrations): 2-Methylbutandiol 1,4: 0.4%; Methylpentandiol: 0.2%

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Sulzfeld/Germany
- Age at study initiation: 12 weeks
- Weight at study initiation: male: 204 g (mean); female: 180 g (mean)
- Housing: 5 animals per cage in V-II-A stainless steel wire mesh cages (supplied by Becker and Co., Castrop-Rauxel/Germany)
- Diet: SSNIFF R, Ssniff Versuchstierdiaeten, Soest/Germany
- Water: Fully demineralized water each workday, ad libitum; tap water on public holidays, ad libitum.
- Acclimation period: Acclimatization in the animal care unit for at least one week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 26 °C
- Humidity (%): 45 - 75 %
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25, 20, 15, 13, 10 %


MAXIMUM DOSE VOLUME APPLIED: 10 ml

Doses:

1000, 1300, 1500, 2000, 2500 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: <15 min, 15 min, 30 min, 1 h, 2 h, 4 h and 5 h after administration of test substance and then once each workday. Check for moribund and dead animals twice each workday and once daily at weekends and on public holidays.
- Frequency of weighing: days 0, 3, 7, 13
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

no data

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 500 mg/kg bw

95% CL:

1 360 - 1 680

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

1 670 mg/kg bw

95% CL:

1 420 - 2 040

Effect levels 3

Sex:

male

Dose descriptor:

LD50

Effect level:

1 350 mg/kg bw

Mortality:

see details in remarks on results.

Clinical signs:

other: Male animals: dyspnea, apathy, abnormal position, staggering, atony, unusual pain reflex, unusual cornea reflex, narcotic-like state, tremor, scrubby fur, exsiccosis, exophthalamus, poor general state. Female animals: dyspnea, apathy, abnormal position,

Gross pathology:

Animals that died: general congestive hyperemia.
Sacrificed animals: nothing abnormal detected.

Any other information on results incl. tables

Mortality:

Dose (mg/kg bw)	1 h		24 h		48 h		7 days		14 days
	male	female	male	female	male	female	male	female	male	female
2500	0	0	5	5	5	5	5	5	5	5
2000	0	0	5	4	5	4	5	4	5	4
1500	0	0	5	2	5	2	5	2	5	2
1300	0	0	1	0	1	0	1	0	1	0
1000	0	0	0	0	0	0	0	0	0	0

 

 Mean Body Weights:

Dose (mg/kg bw)	day 0		day 3		day 7		day 13
	male	female	male	female	male	female	male	female
2500	200	180	-	-	-	-	-	-
2000	170	180	-	200	-	220	-	229
1500	210	180	-	200	-	217	-	222
1300	220	180	253	205	288	214	323	218
1000	220	180	238	205	277	217	327	228

The application of the test substance caused systemic toxicity, including mortality, in a dose dependent manner.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The oral LD50 value for 1,4-Butanediol administered to male and female Sprague-Dawley rats is 1500 mg/kg bw. Administration of the substance produced systemic toxicity in a dose-dependent manner.

Executive summary:

1,4 -Butanediol was administered at 1000, 1300, 1500, 2000, and 2500 mg/kg bw in an aqueous solution to a test group of male and female Sprague-Dawly rats consisting of 5 animals/sex by single gavage application. The animals were observed for mortality and for clinical symptoms (dyspnea, apathy, abnormal position, staggering, atony, unusual pain reflex, unusual cornea reflex, narcotic-like state, tremor, scrubby fur, exsiccosis, exophthalamus, poor general state) of toxicity. They were weighed prior treatment and thereafter, day 3, day 7 and day 13 post-treatment. At the end of the observation period of 14 days, the surviving animals were sacrificed for the purpose of necropsy; animals that died during the observations period also were subjected to necropsy. The LD50 value was estimated to 1500 mg/kg bw on the basis of the observed mortalities.