In 1986, California voters approved an initative to address concerns about unintended exposure to toxic chemicals. Proposition 65 (also known as the Safe Drinking Water and Toxic Enforcement Act of 1986) requires the State to publish a list of chemicals known to cause cancer or birth defects or other reproductive harm. There are over 700 chemicals on this list. Proposition 65 requires businesses to notify Californians about significant amounts of chemicals in the products that they purchase. Prop 65 also prevents businesses from knowingly discharging toxic compounds into drinking water or onto land where they can pass into drinking water.

Proposition 65 affects dietary supplements because some natural products contain toxic compounds, although these may be present in very low levels. Lead and other heavy metals, aflatoxins and pesticide residues are some examples of toxin compounds that can be found in natural products. The State of California requires the Californian public has the right to know about all products containing naturally occurring or introduced toxic compounds. The following warning must be placed on these products: WARNING: THIS PRODUCT [MAY] CONTAIN[S] CHEMICALS KNOWN TO THE STATE OF CALIFORNIA TO CAUSE CANCER AND BIRTH DEFECTS OR OTHER REPRODUCTIVE HARM. Products which are tested and found not to contain toxic compounds listed in Prop 65 do not need to carry this label.