Registration Dossier

Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Remarks:
exposure route (i.p.) not relevant for human exposure

Data source

Reference
Reference Type:
secondary source
Title:
Serum enzymes as indicators of chemically induced liver damage
Author:
Drotman, R. and Lawhorn, G.
Year:
1978
Bibliographic source:
Drug and Chemical Toxicology, 1(2) : 163-171 (166)

Materials and methods

Principles of method if other than guideline:
Study was preformed to investigate liver enzymes as biomarkers for liver damage.

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: Cox
Sex:
male

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
physiological saline
Doses:
0, 250, 500 and 1000 mg/kg bw
No. of animals per sex per dose:
20 (males only)
Control animals:
not specified

Results and discussion

Mortality:
no data
Clinical signs:
no data
Body weight:
no data
Gross pathology:
no data

Any other information on results incl. tables

Liver histopathology:

At 250 mg/kg bw dilated sinusoids after 2 h and mild degeneration/disruption of lobular pattern after 6 h. From 12 hours post-dosing no abnormalities were noted.

At 500 mg/kg bw mild degeneration/disruption of lobular pattern after 2 h, periportal necrosis and hydropic degeneration at 6 h and dilated sinusoids at 12 h. At 24 and 48 h post-dosing no abnormalities were noted.

At 1000 mg/kg bw periportal necrosis and hydropic degeneration at 2 h, disruption of lobular pattern at 6 h and dilated sinusoids at 12 and 24 h. At 48 h no abnormalities were detected.

Haematology: significantly increased ornithine carbamyl transferase at 2, 6 and 12 h (500 and 1000 mg/kg); significantly increased aspartate aminotransferase at 2, 6 and 12 h (500 and 1000 mg/kg); significantly increased alanina aminotransferase at 1000 mg/kg at 2, 6 and 12 hours; significanlty increased sorbitol dehydrogenase at 500 mg/kg at 6 h; effects decreased with increased sampling time.

 

Applicant's summary and conclusion

Conclusions:
Intraperitoneal administration of the test substance induced histopathological liver abnormalities and liver enzyme changes.
Executive summary:

The study was performed to investigate liver enzymes as biomarkers for liver damage. Male rats were exposed to different doses of the test substance (250, 500 and 1000 mg/kg bw) intraperitoneal and sacrificed after 2, 6, 12, 24 and 48 hours of dosing.

The time and magnitude of peak liver injury were assessed by histopathological examination of the liver. Moreover, serum enzyme measurements were performed. Histopathological abnormalities were detected for all dosages. The highest dose tested caused periportal necrosis and hydropic degeneration in animals sacrificed 2 h after substance application. Liver enzymes were induced. With increasing sampling time the effects on the liver and liver enzymes decreased. No mortality data are recorded, thus no LD50 after intraperitoneal administration was derived.