The primary and most effective strategy to control exposure to toxic substances in the workplace is Substitution with a less hazardous chemical (Option 2).

In occupational health and safety, controlling exposure to hazardous substances follows a hierarchy of controls. This hierarchy prioritizes methods based on their effectiveness in eliminating or reducing risks.

1. Substitution involves replacing a toxic substance with a less harmful one. This approach directly removes or reduces the hazard at its source, making it inherently safer for workers. When feasible, substitution is preferred because it minimizes the need for ongoing protective measures and reduces the possibility of exposure.

2. Although engineering controls (Option 1) are highly effective—such as enclosing or isolating the chemical—these controls do not eliminate the hazard entirely but rather reduce exposure.

3. Personal protective equipment (PPE) (Option 3) is the least effective control because it relies on correct and consistent use by workers and does not remove the hazard itself.

4. Administrative controls (Option 4), like job rotation or work scheduling, reduce exposure time but again do not eliminate the hazard.

Therefore, substitution is considered the best strategy because it fundamentally changes the hazard to reduce or eliminate risk, aligning with the top tier of the hierarchy of controls.

Reference: Occupational Health and Safety Management Systems, Volume 3, Chapter 5, p. 150-155