But-2-yne-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 publication in peer reviewed journal.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1992

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Method: other: no data

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

But-2-yne-1,4-diol

EC Number:

203-788-6

EC Name:

But-2-yne-1,4-diol

Cas Number:

110-65-6

Molecular formula:

C4H6O2

IUPAC Name:

but-2-yne-1,4-diol

Details on test material:

- Analytical purity: 99%

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Nofer Institute of Occupational Medicine husbandry
- Age at study initiation: no data
- Weight at study initiation: Males = 322 +/1.43 g, females = 209 +/- 21 g
- Fasting period before study: 16 hours
- Housing: polypropylene cages with sawdust as bedding, 5 rats/cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7-14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21
- Humidity (%): 45-55
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: No data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Butyndiol was administered by gavage in 10% aqueous solution.

Doses:

100, 150, 180, 200, and 250 mg/kg bw

No. of animals per sex per dose:

5 males, 5 females

Control animals:

not specified

Details on study design:

Daily observations for mortality and toxic signs were made throughout the 14-day observation period. Two additional groups of five male and five female rats were given the test substance at the dose of 100 mg/kg in order to assess the pathological lesions 48 h and 14 days after administration. A detailed necropsy of each animal was performed and the macroscopic appearance of internal tissues was noted. Tissues and organs were fixed in 10% neutral buffered formalin, processed and embedded in paraffin wax.

Statistics:

LD50 values determined using the probit method.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

132 mg/kg bw

Based on:

test mat.

95% CL:

89 - 158

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

176 mg/kg bw

Based on:

test mat.

95% CL:

118 - 270

Mortality:

Deaths occurred within 48 hours of oral dosing.

Gross pathology:

Gross pathological findings in animals that died included diarrhea, fluid-filled gastrointestinal tract and congestion of internal organs.

Other findings:

Histological investigations resulted in the observance of strong degenerative changes in the liver and kidneys. The direct cause of death was probably toxic shock syndrome and extensive necrosis of the liver parenchyma.

Histopathological changes:
-perivascular oedema and extensive bronchopneumonia in lungs
-passive hyperaemia and focal to diffuse centrilobular and midzonal necrosis in liver
-nephrosis (in all dead animals) characterized by degeneration, necrosis and sloughing of the epithelium of convoluted proximal tubules. There were dilations and hyaline and granular casts in the tubules.

Other hepatic abnormalities:
-balloon cells

Any other information on results incl. tables

The pathological lesions in rats killed after 48 h and 14 days after administration of 1,4-butynediol at a dose of 100 mg kg were observed in the liver and kidneys. After 48 h the hepatic changes ranged from vacuolar degeneration through centrilobular and midzonal focal necrosis to panlobular necrosis. The necrotic foci were accompanied by infiltration with reactive mononuclear cells and single granulocytes. Fatty changes at the edges of the necrotic foci were also seen. There were numerous mitotic cells in the intact parenchyma. Liver lesions that observed after 14 days were characterized by periportal cytoplasmic vacuolation, slight lymphocytic infiltrations, especially near the vessels, numerous polynucleated hepatocytes and single cells in mitosis.

 

In the renal cortex, sloughing of tubular epithelium were observed in three of the five male rats 48 h after dosage. After 14 days, epithelial regeneration was observed in one male rat.

 

Applicant's summary and conclusion

Interpretation of results:

toxic

Remarks:

Migrated information Category 3 Criteria used for interpretation of results: EU