Butane-1,4-diol

Endpoint summary

Description of key information

LD50, oral rat: 1500 mg/kg bw

LC50, inhal rat: >5.1 mg/L and >15 mg/L

LD50, dermal rat: >2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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

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

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

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

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 500 mg/kg bw

95% CL:

1 360 - 1 680

Sex:

female

Dose descriptor:

LD50

Effect level:

1 670 mg/kg bw

95% CL:

1 420 - 2 040

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 500 mg/kg bw

Quality of whole database:

Key value based on a reliable study and supported by data from a publication.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 433 draft (Acute Inhalation Toxicity: Fixed Concentration Procedure) (not officially approved)

GLP compliance:

not specified

Test type:

fixed concentration procedure

Species:

rat

Strain:

other: Crl:CD

Sex:

male

Details on test animals or test system and environmental conditions:

Rats were 7-8 weeks old and weighing between 233 and 271 grams. Male albino Crl:CD@ rats were housed in pairs in 8" x 8" x 14" stainless steel wire mesh cages. Purina Certified Rodent Chow@ 15002 and water were available ad libitum. Rats were weighed and observed for general suitabilityfor at least 1 week prior to test. Animals were restrained in stainless steel holders.

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

not specified

Details on inhalation exposure:

Rats were exposed nose-only to atmospheres containing refined 1,4-butanediol for single, 4h periods.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

At 30-minute intervals, calibrated volumeS of test atmosphere were drawn through pre-weighed glass fiber filters. Filters were weighed both wet and dry on a Cahn 26 Automatic Electrobelance@ . Atmospheric concentrations were determined from dry weight ga

Duration of exposure:

4 h

Concentrations:

4.6 mg/L, 9.4 mg/L and 15 mg/L

No. of animals per sex per dose:

Summary reports 6 male rats whereas experimental detail reports 10.

Control animals:

no

Details on study design:

Duration of observation period following administration: 14 days
- Frequency of observations and weighing:daily
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: yes

Statistics:

LC 50 Calculated by the method of Finney, D. J., Probit Analysis, 3rd Edition, Cambidge University Press (1971)

Sex:

male

Dose descriptor:

LC50

Effect level:

> 15 mg/L air

Exp. duration:

4 h

Remarks on result:

other: Mortality 1/10, 1 day post exposure

Key result

Sex:

male

Dose descriptor:

discriminating conc.

Effect level:

9.4 mg/L air

Exp. duration:

4 h

Remarks on result:

other: Mortality 0/10

Sex:

male

Dose descriptor:

other: No Observed Adverse Effects

Effect level:

4.6 mg/L air

Exp. duration:

4 h

Remarks on result:

other: Mortality 0/10

Mortality:

at 15mg/L 1/10 1day post exposure

Clinical signs:

other: During Exposure: Clinical observations could not be made due to the density of chamber atmospheres. When removed from restrainers, all rats exposed to 9.4 and 15 mg/L exhibited lethargic or no movement and labored breathing. At 15 mg/L, rats exhibited red

Body weight:

In a dose dependent manner, all rats exhibited slight to severe weight loss 1 day post exposure, followed by the resumption of a normal rate of weight gain.

Gross pathology:

no data

An inhalation LC50 of refined 1,4-butanediol could not be calculated from these data as there was only 1/10 mortality at highest dose tested. Higher atmospheric concentrations could not be generated.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

9 400 mg/m³ air

Quality of whole database:

An inhalation LC50 of refined 1,4-butanediol could not be calculated from these data as there was only 1/10 mortality at highest dose tested. Higher atmospheric concentrations could not be generated.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

LD50 was > 2000 mg/kg bw based on a reliable study and supported by data from a publication indicating an LD50 for rats at 2000 mg/kg bw .

Additional information

1,4-Butanediol (BDO) has been adequately characterized for acute toxicity via oral, dermal, and inhalation routes. BDO is moderately toxic via oral gavage, but only slightly acutely toxic via dermal or inhalation exposure. In rats, oral LD50s are >1500 mg/kg bw (BASF SE, 1981 and Jedrychowski, et. al., 1990), LC50s are >5.1 mg/L (BG Chemie, 1991 and DuPont, 1982), and dermal LD50s are > 2000 mg/kg bw (BASF SE, 1981 and Jedrychowsi, et. al, 1990). Clinical signs reported in these acute studies include: (oral) dyspnea, apathy, abnormal position, staggering, atony, unusual pain reflex, unusual cornea reflex, narcotic-like state, tremor, scrubby fur, exsiccosis, exophthalamus, poor general state; (dermal) dyspnea, unsettled behaviour, poor general state, very slight erythema; (inhalation study 1) accelerated or shallow respiration, nasal discharge, ruffled fur, staggering unsteady gait and deteriorated general state; (inhalation study 2) lethargy or no movement, labored breathing, red discharge from the perineal area, lung noise, dry red or brown nasal discharge, and wet perineum.

Justification for classification or non-classification

Acute oral toxicity

Based on the results of acute oral toxicity testing (LD50 = 1500 mg/kg), 1,4 butanediol is classified as Acute Toxicity Category 4 (Harmful if swallowed) under the EU CLP classification criteria (EU Regulation 1272/2008).

Acute inhalation toxicity

Based on the presence ofeffects, including drowsiness or dizziness in animal studies, 1,4-butanediol would be rated STOT Single Exposure 3 according to the EU CLP classification criteria (EU Regulation 1272/2008).

Acute dermal toxicity

Based on the results of the key study (rat dermal LD50 >2000 mg/kg), 1,4-butanediol would not be classified under the EU CLP classification criteria (EU Regulation 1272/2008).