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Lethality, hexobarbital narcosis and behavior in rats exposed to atrazine, bentazon or molinate
1Dipartimento di Medicina e Oncologia Sperimentale, Sezione di Patologia Ambientale, Torino, Italy.
Abstract:
Previous findings from our laboratory suggested a possible interaction of atrazine, bentazon and molinate with other environmental and/or occupational poisons. The aim of this research was to obtain further toxicological information by using phenobarbital-induced rats and to characterize the effects of these herbicides on the hepatic microsomal metabolism of xenobiotics. Acute experiments have shown that the LD50 is augmented by the barbiturate pretreatment when atrazine is used, remains unchanged in the case of bentazon, but is lowered when molinate is given. Recrystallized atrazine, in the absence of the wetting compounds, elicits the same acute toxicity found when animals are challenged with a commercial preparation. No significant sex-related differences have been observed. In long-term treatment with these toxicants, atrazine shortened the hexobarbital narcosis, but no effect was observed after administration of either bentazon or molinate. Further studies on hexobarbital sleeping time demonstrated that females are more susceptible than males to the narcotic effect of this compound. The induction-like effect of atrazine exposure has been confirmed, mainly in young animals. At the end of the sleeping time, the actual serum concentration of hexobarbital is practically the same, and is not related to the length of the sleeping time. The absence of behavioral alterations in the open field tests exclude possible neurological effects of the triazine herbicide. In conclusion, these data demonstrate that atrazine by itself induces the hepatic pharmacometabolic system, while its metabolites result less toxic than the parent compound. On the contrary, metabolic transformations render the toxic effects of bentazon more severe.
Insights
Atrazine exposure induces liver metabolism, affecting drug interactions, while bentazon becomes more toxic after metabolic transformation. Molinate
Area of Science:
- Environmental Toxicology
- Pharmacology
- Biochemistry
Background:
- Previous research indicated potential interactions between herbicides (atrazine, bentazon, molinate) and other environmental/occupational toxins.
- Understanding these interactions is crucial for assessing the overall toxicological risk posed by common agricultural chemicals.
Purpose of the Study:
- To investigate the effects of atrazine, bentazon, and molinate on hepatic microsomal metabolism of xenobiotics in rats.
- To characterize the toxicological profiles of these herbicides, particularly in relation to drug metabolism and acute toxicity.
Main Methods:
- Utilized phenobarbital-induced rats to assess acute toxicity (LD50) and long-term effects of herbicide exposure.
- Measured hexobarbital-induced narcosis duration and sleeping times to evaluate impacts on xenobiotic metabolism.
- Conducted open field tests to assess potential neurological effects.
Main Results:
- Atrazine augmented LD50 with barbiturate pretreatment and shortened hexobarbital narcosis, indicating induction of hepatic metabolism.
- Bentazon showed unchanged LD50 but its metabolites were found to be more toxic.
- Molinate lowered LD50, and neither bentazon nor molinate affected hexobarbital narcosis in long-term studies.
Conclusions:
- Atrazine, as a triazine herbicide, directly induces the hepatic pharmacometabolic system, with its metabolites being less toxic.
- Metabolic processes exacerbate the toxic effects of bentazon.
- No significant neurological effects were observed for atrazine, and sex did not play a significant role in acute toxicity.