Myelosuppressive activity of two herbicides, atrazine and dinoterb, on human haematopoietic progenitor cells: An in vitro assay to evaluate the effects of intermediate or long-term exposure.
The effects of chronic exposure to phytosanitary products are difficult to determine because of their use in combination with other products and their variety of formulations containing additives or contaminants. In order to evaluate, at the cellular level, the risk of myelosuppressive effects caused by two widely used herbicides, atrazine and dinoterb, we performed in vitro assays on human granulo-monocytic progenitor-cells (CFU-GM) and also granulomonocytic expansion in liquid media. Both of these techniques were carried out in the presence of each molecule. Seven stable environmental metabolites of atrazine were studied using the above techniques in addition to supernatants of rat hepatocytes preincubated with atrazine and dinoterb for 24 hr. Parent atrazine and dinoterb showed similar moderate-direct toxicity on CFU-GM. In cells grown in liquid media for a period longer than 14 days, dinoterb toxicity appeared delayed but increased when compared with atrazine. 2-chloro-diamino-atrazine was found to be as toxic as atrazine on CFU-GM. Supernatants of rat hepatocyte preincubated for 24 hr with dinoterb exhibited a 150-fold increase in toxicity compared with the parent molecule, while toxicity remained unchanged for atrazine. This phenomenon was directly correlated to toxicity on rat hepatocytes. The present study will be useful in defining tissue-specific toxicities of phytosanitary products, including environmental or biotransformed metabolites.
Sawicki
B
B
Departement de Pharmaco-Toxicologie, Institut de Synergie des Sciences et de la Santé, C.H.U., 5 avenue Foch, 29609 Brest Cedex France.
Durand
G
G
Dewitte
J D
JD
Ratanasavanh
D
D
Riche
C
C
Léglise
M C
MC