[4] Profenofos can be used on a variety of crops including cotton and vegetables such as maize, potato, soybean, and sugar beet.

[6]: 332 A 2007 World Health Organization report found no adverse effects to workers of routine exposure to profenofos and no teratogenicity or carcinogenicity.

[5]: 435–8 Based on a study of patients poisoned with profenofos and its close chemical relative prothiofos, the compound has been described as "of moderately severe toxicity", causing respiratory failure.

Differences in chemical structure that distinguish these two compounds from more common organophosphate pesticides - namely, the presence of the S-alkyl group on the phosphorus atom where most OP compounds possess a methoxy or ethoxy group - underlie differences in their behavior as acetylcholinesterase enzyme inhibitors compared to the rest of the OP class.

[9] A United States Environmental Protection Agency report identified profenofos as toxic to birds, small mammals, bees, fish, and aquatic invertebrates, noting several fish kill incidents in which profenofos exposure, primarily due to runoff, was implicated as a probable cause.