Extracted from Law360
On May 8, the California Office of Environmental Health Hazard Assessment, or OEHHA, issued two notices of intent to list. The notices propose to add hydrochlorothiazide, voriconazole, tacrolimus and welding fumes to the list of chemicals known to the state of California to cause cancer under Proposition 65.
If finalized, the proposed listings could trigger new warning and compliance obligations for businesses that manufacture, distribute, sell or use these substances or related processes and products.
Businesses should carefully assess potential risks of exposures to medications via nontraditional pharmaceutical dispensing channels, releases of welding chemicals that could lead to occupational or environmental exposures, and possible downstream exposures to both types of substances from manufacturing operations.
Public comments were due by June 8.
Proposition 65 Overview
Passed in 1986, California's Safe Drinking Water and Toxic Enforcement Act, commonly known as Proposition 65, requires the state to maintain and publish a list of chemicals known to cause cancer or reproductive toxicity.
Businesses with 10 or more employees that knowingly and intentionally expose individuals to a listed chemical must provide a "clear and reasonable" warning before the exposure occurs, unless an affirmative defense applies. Proposition 65 also prohibits the knowing discharge of listed chemicals into sources of drinking water.
One way chemicals are added to the Proposition 65 list is through the Labor Code mechanism. Under this mechanism, substances identified by the International Agency for Research on Cancer as human or animal carcinogens must be listed under Proposition 65. OEHHA has adopted regulations governing these listings.
Chemicals Proposed for Listing
OEHHA's two notices of intent to list cover the following four substances.
Hydrochlorothiazide
Hydrochlorothiazide is a thiazide diuretic, commonly called a "water pill," used to treat high blood pressure (hypertension) and fluid retention (edema) caused by congestive heart failure, liver disease, kidney disease or steroid treatment. IARC classified hydrochlorothiazide as Group 1 — carcinogenic to humans.
Voriconazole
Voriconazole, sold under the brand name Vfend, is an antifungal medication used to treat serious fungal or yeast infections, including aspergillosis, candidemia and esophageal candidiasis. IARC classified voriconazole as Group 1.
Tacrolimus
Tacrolimus, sold under the brand name Protopic in topical form, is an immunosuppressant used topically to treat moderate to severe atopic dermatitis. IARC classified tacrolimus as Group 1.
Welding Fumes
Welding fumes are complex mixtures of metallic oxides, silicates and fluorides generated during welding operations. IARC classified welding fumes as Group 1 in Monographs Volume 118, finding sufficient evidence of carcinogenicity in humans.
Scientific and Regulatory Basis for Listing
All four proposed listings rely on the Labor Code mechanism. OEHHA concluded that each substance qualifies for listing because IARC classified each as Group 1.
The IARC evaluations for hydrochlorothiazide, voriconazole and tacrolimus were published in Monograph Volume 137 in November 2024. The IARC evaluations for welding fumes were published in Monograph Volume 118 in July 2018.
Prescription Drug Warning Safe Harbor
Proposition 65's implementing regulation states that, for prescription drugs, "the labeling approved or otherwise provided under federal law and the prescriber's accepted practice of obtaining a patient's informed consent comply with this subarticle."
Thus, manufacturers whose drugs bear labeling approved by the U.S. Food and Drug Administration and that are dispensed through the prescriber-patient informed consent process are deemed to satisfy Proposition 65's clear and reasonable warning requirement.
The California Court of Appeal, Second District, upheld this safe harbor in 2005 in In re: Vaccine Cases, holding that the predecessor regulation was a valid exercise of OEHHA's authority to define "clear and reasonable warning" for prescription drugs — not an unauthorized exemption.
The court explained that physicians prescribing drugs already have an obligation to inform patients about adverse side effects, which reasonably includes warning about the drug's carcinogenicity or reproductive toxicity.
The regulation also states that no warning is required in emergency medical settings where the patient is unconscious, the procedure must be undertaken immediately, or there is insufficient time to obtain consent.
If hydrochlorothiazide, voriconazole and tacrolimus are listed, entities dispensing them through the traditional prescriber-patient channel should consider whether they can rely on the safe harbor without adding a separate Proposition 65 cancer warning. Exposures outside this channel — such as nonprescription dispensing, combination products or industrial uses — may require a separate analysis.
Federal Preemption Considerations for Prescription Drugs
Companies should also consider whether federal law may preempt some Proposition 65 chemical listings for prescription drug products. The federal Food, Drug, and Cosmetic Act's express preemption provision contains a savings clause that preserves Proposition 65 from express preemption because Proposition 65 was adopted before Sept. 1, 1997.
Even so, the California Supreme Court held in 2004, in Dowhal v. SmithKline Beecham Consumer Healthcare, that the savings clause does not entirely rule out conflict preemption. A Proposition 65 warning may be preempted if it directly conflicts with or frustrates the purpose of an FDA requirement, provided the conflict rests "on a basis relevant to consumer health, and not because the [warning] would frustrate the FDA's policy favoring national uniformity."
At the same time, the court noted that "in most cases FDA warnings and Proposition 65 warnings would serve the same purpose — informing the consumer of the risks involved in use of the product — and differences in wording would not call for federal preemption."
Two additional principles frame the drug-specific analysis. First, brand-name manufacturers may use the FDA's changes-being-effected process to strengthen labeling to reflect newly acquired safety information, so impossibility preemption generally does not apply to them.
Second, under the U.S. Supreme Court's 2011 ruling in PLIVA Inc. v. Mensing, and the California Court of Appeal's 2023 ruling in Center for Environmental Health v. Perrigo Co., generic manufacturers are subject to a federal duty of sameness that prohibits them from unilaterally deviating from brand-name labeling.
If no method of providing a Proposition 65 warning exists that does not violate this duty, the claim may be preempted through impossibility preemption — at least until the brand-name manufacturer adds a warning.
Industry Implications if OEHHA Lists the Chemicals
Pharmacies, Healthcare Facilities and Pharmaceutical Manufacturers
Companies that manufacture, package, label, distribute or sell products containing hydrochlorothiazide, voriconazole or tacrolimus should evaluate whether Proposition 65 warnings may be required.
Retail pharmacies, hospitals and clinics that dispense these medications may also need to consider whether Proposition 65 warnings are necessary for patients or staff, depending on the nature and level of exposure.
Open questions remain about whether the safe harbor informed consent standard applies in nontraditional dispensing channels such as mail-order pharmacies, telehealth and automatic refills; whether it applies in nonprescription or industrial contexts; and whether the preemption landscape could shift if the FDA takes a specific position on the appropriateness of Proposition 65 cancer warnings for any of these drugs.
Welding and Manufacturing Operations
Companies involved in welding — including construction, automotive, aerospace, shipbuilding and general manufacturing — should assess occupational and bystander exposure to welding fumes.
They should also consider whether warning obligations extend to workers, building occupants or nearby community members, and whether discharges to water sources raise Proposition 65 issues.
Product Suppliers and Retailers
Businesses in the supply chain for products containing one or more of these chemicals — including manufacturers of combination pharmaceutical products, industrial equipment or welding supplies — should evaluate whether downstream exposure could trigger warning obligations.
Next Steps
OEHHA's comment period closed on June 8. In responding to comments, OEHHA will consider only whether IARC has sufficiently identified the substance as a human or animal carcinogen, and will not consider challenges to the underlying weight of evidence.
Businesses should monitor OEHHA's response to comments, the final listing decision, and any subsequent action to establish safe harbor levels for the chemicals, if they are listed.