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Toxicological information

Acute Toxicity: other routes

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Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
no data
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Abstract

Data source

Reference
Reference Type:
other: abstract
Title:
Effects of thiourea tolerance on plasma histamine, and lung vascular permeability.
Author:
Giri, S.N. et al.
Year:
1991
Bibliographic source:
Arch Toxicol. 1991;65(7):603-5.

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
No details on method are available.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
no data

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
no data

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
not specified
Details on exposure:
no data
Doses:
first experiment: 10.0 mg/kg;
second experiment: with pre-treatment dose 0.5 mg/kg; challenge with 10 mg/kg
No. of animals per sex per dose:
no data
Control animals:
not specified
Details on study design:
no data
Statistics:
no data

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LD100
Effect level:
10 mg/kg bw
Based on:
test mat.
Mortality:
after intraperitoneal application of 10 mg/kg 100 % mortality within 24h
Clinical signs:
no data
Body weight:
no data
Gross pathology:
no data
Other findings:
no data

Any other information on results incl. tables

Adult male rats treated with a lethal edematogenic dose of thiourea (TU) (10.0 mg/kg, intraperitoneally) responded with significant elevations in plasma histamine, lung vascular permeability and 100% mortality over a subsequent 24-h period. When rats were pretreated with a small non-lethal dose of TU (0.5 mg/kg) and subsequently challenged with the lethal dose at 1, 4, 8, 16 and 32 days later, there was complete protection against death for at least 8 days and partial protection for an additional 24 days. This decrease in mortality correlated quite closely with reduced plasma histamine levels and diminished pulmonary vascular permeability. The results suggest that reduced exposure of the pulmonary vasculature to histamine may offer a partial explanation for tolerance to thiocarbamide compounds in the rat.

Applicant's summary and conclusion

Conclusions:
Thiourea is toxic to the rat when administered intraperitoneally at concentrations of 10 mg/kg bw. The LD100 is 10 mg/kg bw.
Executive summary:

Thiourea was administered to male Sprague-Dawley rats at a dose of 10 mg/kg bw. intraperitoneally. This resulted in 100 % mortality within 24 h. When rats were pretreated with a small non-lethal dose of thiourea (0.5 mg/kg) and subsequently challenged with the lethal dose at 1, 4, 8, 16 and 32 days later, there was complete protection against death for at least 8 days and partial protection for an additional 24 days. Therefore it was concluded that the decrease in mortality correlated quite closely with reduced plasma histamine levels and diminished pulmonary vascular permeability. The authors concluded that the degree of tolerance to thiourea developed is related to plasma histamine concentration and pulmonary vascular permeability.