Atrazine is primarily responsible for the toxicity of long-term exposure to a combination of atrazine and inorganic arsenic in the nigrostriatal system of the albino rat

• Chronic exposure to ATR or iAs disrupts the nigrostriatal DAergic system in rats.
• Chronic coexposure to ATR + iAs results in antagonistic effects on locomotor activity.
• The nigrostriatal DAergic system is more sensitive to ATR than to iAs.
• These results can assist decision-making in the assessment of health risks.

Chronic and simultaneous exposure to a variety of chemicals present in the environment is an unavoidable fact. However, given the complexity of studying chemical mixtures, most toxicological studies have focused on the effects of short-term exposure to single substances. The aim of this study was to evaluate the effects on the nigrostriatal system of the chronic, simultaneous exposure to two widely distributed substances that have been identified as potential dopaminergic system toxicants, inorganic arsenic (iAs) and atrazine (ATR). Six groups of rats were treated daily for one year with atrazine (10 mg ATR/kg), inorganic arsenic (0.5 or 50 mg iAs/L of drinking water), or a combination of ATR + 0.5 mg iAs/L or ATR + 50 mg iAs/L. The 50 mg iAs/L group showed locomotor hypoactivity, while all treatments decreased motor coordination in contrast no effects of treatment were found on the place and response learning tasks. Regarding markers for liver and muscle damage, there were no differences between groups in creatine kinase (CK) or aspartate transaminase (AST) activities, while decreases in lactate dehydrogenase (LDH) levels were found in some exposed groups. The striatal DA content was significantly reduced in ATR, 0.5 mg iAs/L, ATR + 0.5 mg iAs/L, and ATR + 50 mg iAs/L groups, in comparison to the control group. The number of mesencephalic tyrosine hydroxylase positive cells decreased in the ATR and ATR + 0.5 mg iAs/L groups compared to the control. In contrast, immunoreactivity to cytochrome oxidase was reduced compared to the control in all treated groups, except for the group treated with 0.5 iAs mg alone. Our results indicate that ATR has deleterious effects on dopaminergic neurons and that the combination of ATR and iAs does not exacerbate these effects.