Naproxen's byproducts could pose threat to aquatic creatures

Naproxen is a popular, over-the-counter anti-inflammatory drug used to treat pain found in common brands like Aleve and Anaprox. Once excreted, the drug usually passes through wastewater treatment facilities intact since most facilities aren’t equipped to remove pharmaceuticals like it. As a result, the chemical eventually ends up in waterways or in the ocean. In fact, naproxen is one of the most frequently detected pharmaceuticals in the environment, says Allison Welch, a biologist at the College of Charleston in South Carolina.

Now Welch and her colleagues have found that when hit with light, naproxen breaks down to molecules that are more toxic to aquatic life than the drug itself (Environ. Toxicol. Chem. 2019, DOI: 10.1002/etc.4514).

The findings, Welch says, highlight the fact that scientists should look more deeply at the effects of drugs that get into ecosystems. “If we only had information on the parent compound, we would be underestimating the toxicity in the ecosystem,” she says.

“Throughout the world, pharmaceuticals of all kinds are entering the environment. It is crucial to understand how these compounds will behave once released,” says Emma Rosi, a senior scientist at the Cary Institute of Ecosystem Studies who was not involved in the recent study. Other research groups have shown that phototransformation products of molecules like the cancer drug tamoxifen can be harmful to aquatic organisms. For example, photolysis byproducts of high-blood pressure drug atenolol and pain and arthritis treatment drugs ketoprofen and diclofenac can harm zebrafish in lab studies.

Previously, Welch’s College of Charleston colleague Wendy Cory had found that naproxen produces byproducts when degraded under light. Welch, Cory and their colleagues wanted to see if these phototransformation products would have an effect on southern toad (Anaxyrus terrestris) tadpoles. The tadpoles’ aquatic ecosystems may make them susceptible to absorbing these chemicals downstream from wastewater treatment plants, Welch says.

The researchers put the tadpoles in water with either naproxen or different naproxen byproducts for 4 days. They found that half of the tadpoles were either immobilized or killed by concentrations of one phototransformation product at 20.7 mg/L, while the other product immobilized half the tadpoles at 8.4 mg/L. These data demonstrated the byproducts’ increased toxicity compared with naproxen, which immobilized half the tadpoles at 129 mg/L.

Welch says that the highest reported concentration of naproxen in the environment has been 32 µg/L, but that chronic effects from it have been reported in invertebrates at concentrations as low as 100 µg/L. The team looked only at immobilization or death from the naproxen byproducts, but Welch says it would be great for someone to study less acute effects.

“This study highlights the complexities of transformations, and resulting effects, that can occur once we release compounds into the environment,” Rosi says, adding that more of this type of work is needed.