1) Assessment of acute toxicity of SMX and TMP in WISTAR strain rats and dd-strain mice revealed the following LD50 :
Rats male female
SMX
p. o. 8640 8400
i. p. 2790 2690
s. c. >5000 >5000
TMP
p. o. 1670 1670
i. p. 1530 1460
s. c. 5000 5000
ST (5 : 1)
p. o. 7300 7200
i. p. 2450 1840
s. c. >3000 >3000
Mice male female
SMX
p. o. 3900 3471
i. p. 2300 2450
s. c. 5000 5000
TMP
p. o. 5200 5400
i. p. 1870 2200
s. c. 5000 5000
ST (5 : 1)
p. o. 7200 6400
i. p. 2010 2197
s. c. >3000 >3000
No potentiation of acute toxicity was apparent from the combination of the 2 drugs. There was neither difference in the expression of acute toxicity between male and female animals.
2) The study of subacute toxicity of SMX and TMP in rats revealed that all compounds, alone and in combination, were tolerated in relatively high doses. Results of peripheral blood examinations indicated that SMX, TMP and their combination gave inhibitory actions on the hematopoietic system in higher doses.
The histopathological abnormalities were largely confined to dose-dependent enlargement of the thyloid gland in animals given SMX. The morphological pictures in groups given SMX-TMP combination appeared to be also dominated by SMX. Histopathological examinations of animals given TMP and SMX-TMP combination did not reveal significant changes in other tissues including brain, heart, thymus, lung, stomach, intestines, liver, pancreas, spleen, adrenal, kidney, male and female reproductive organs and bone marrow. There was no evidence of the potentiation of subacute toxicities by the combination of SMX and TMP.
