Registration Dossier

Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for accessment.

Data source

Reference
Reference Type:
publication
Title:
Hepatic RNA synthesis in rats treated with ethylene thiourea
Author:
Austin GE, and Moyer GH
Year:
1979
Bibliographic source:
Res. Commun. Chem. Pathol. Pharmacol. 23: 639-642.

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Animals (rats) received a single ip injection of ETU (2 doses) in DMSO.
One control group (DMSO).
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
ETU was a gift from Rohm and Haas, Co., Philadelphia, Pa.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Simonsen, Gilroy, Ca.
- Age at study initiation: no data
- Weight at study initiation: 130-200 g
- Fasting period before study: 16h
- Housing: no data
- Diet (e.g. ad libitum): of wayne meal
- Water (e.g. ad libitum): no data
- Acclimation period: no data


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

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
DMSO
Details on exposure:
no
Doses:
2.5 and 250mg/kg
No. of animals per sex per dose:
4-7 animals / dose
Control animals:
yes
Details on study design:
[3H]orotic acid was given 60 min later ETU. Ninety minutes later this administration, the rats were decapited.
Then rates of hepatic RNA synthesis were determined.
Statistics:
no data

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LD0
Effect level:
250 mg/kg bw
Remarks on result:
other: no toxicity observed
Mortality:
No data
Clinical signs:
No clinical signs of toxicity were seen in animals receiving a single injection of ETU (at low or high dosage).
Body weight:
No data
Gross pathology:
The livers of treated rats were grossly and histologically normal at time of sacrifice.
Other findings:
An injection of a low or high dose of ETU produces no significant alteration relative to controls in the pulse labeling of nuclear or cytoplasmic RNA.

Applicant's summary and conclusion

Conclusions:
In the present case, the lack of inhibition of RNA synthesis by ETU suggests that ETU and its metabolites may not alter cellular metabolism.
Executive summary:

Animals (rats) received a single ip injection of ETU (2 doses) in DMSO. DL0 was 250 mg/kg. In the present case, the lack of inhibition of RNA synthesis by ETU suggests that ETU and its metabolites may not alter cellular metabolism.