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Toxicological information

Acute Toxicity: oral

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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:
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

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Analytical purity: 99%

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals 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 levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
132 mg/kg bw
Based on:
test mat.
95% CL:
89 - 158
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