Environmental Science and Technology September 7, 2005 ARE PESTICIDE "INERTS" AN UNRECOGNIZED ENVIRONMENTAL DANGER? Scientists question the continued use of POEA in Roundup, citing data showing harmful effects to frogs. By Rebecca Renner Glyphosate herbicides, such as Monsanto's popular Roundup, have an environmentally friendly reputation because their active ingredients are relatively nontoxic and degrade rapidly in the environment. But University of Pittsburgh biologist Rick Relyea is challenging this view. He has found that Roundup at environmentally relevant concentrations kills or harms tadpoles because of the presence of the surfactant POEA , an ingredient that is defined as inert and doesn't appear on the label (Ecol. Appl. 2005, 15, 618-627; 1118-1124). Relyea's work is one of several studies that shed light on the behavior of "inerts" in the environment, a topic largely ignored by the U.S. EPA, say many environmental toxicologists inside and outside the agency. In 1995, EPA changed the listing of POEA (polyethoxylated tallow amine) from an inert of "unknown toxicity" to one that is of "minimal concern". According to the agency, "the current use pattern in pesticide products will not adversely affect public health or the environment". The agency presently does not have plans to further revise the classification, say EPA officials interviewed for this story. "The inerts evaluation for environmental effects is EPA's dirty little secret," says one agency scientist who requested anonymity. "POEA is likely to be the tip of the iceberg, but we don't know because we don't have data. The agency assures us that everything's okay. On the basis of what? Not data. Then, to make matters worse, the inerts aren't even listed on the label." An agency official who asked not to be quoted admitted that the environmental effects of inerts are not a high priority for EPA. This is not because the agency is ignoring important data, the official says. Instead, EPA regulators say that any problems are not significant or are handled through usage restrictions that appear prominently on product labels. EPA's approach generally makes sense, argues environmental toxicologist Keith Solomon with the University of Guelph (Canada). EPA assumes that pesticide active ingredients are typically potent chemicals and most inerts are fairly benign, which Solomon says is generally true. Glyphosate, with its very low toxicity, violates this assumption. As a result, the inert surfactant makes a big difference to the overall toxicity of any formulation with the compound. However, this case is probably unusual, he states. For regulatory purposes, pesticide formulations consist of two broad components -- "active" ingredients that target the pest or weed and "inerts" or "other" ingredients. Inerts, which often comprise the bulk of the pesticide formulation, improve the efficacy or handling characteristics of the product, for example, by helping the active ingredient dissolve, easing application, or improving the pesticide's adherence to plant leaves. POEA in Roundup enables the herbicide to penetrate the waxy surfaces of plants, according to Monsanto scientific director Eric Sachs. EPA has four lists of inert ingredients: inerts of toxicological concern, potentially toxic inerts, inerts of unknown toxicity, and minimal-risk inerts. An indication of the hazards that many inert ingredients may pose is the extent to which these same chemicals are regulated under other U.S. laws, says Caroline Cox, staff scientist with the advocacy group Northwest Coalition for Alternatives to Pesticides in Eugene, Ore. In March, she scrutinized the more than 1800 chemicals on EPA's list of inerts of unknown toxicity and found that 75 are identified as hazardous by the Clean Air Act, 52 under Superfund, 64 in the Clean Water Act, 43 on the Toxics Release Inventory, and 78 with the Toxic Substances Control Act. In addition, 292 inerts of unknown toxicity are registered by EPA as active ingredients in other pesticides. EPA requires information on possible toxicity for active ingredients but not for inerts. Moreover, most inert ingredients are not identified on labels because manufacturers maintain that these constitute trade secrets. The legality of this position is still being considered by the courts, according to Cox, whose organization has spearheaded the call for disclosure of inerts on pesticide labels. One chemical that appears on the inerts list but is also considered an active ingredient is PBO (piperonyl butoxide), which is a synergist that makes pyrethroid pesticides 10x more lethal to black flies and mosquitoes. Studies of commercial pyrethroid formulations by Eric Paul's group at New York state's Rome Field Station show that PBO also enhances the toxicity of these pesticides to fish. However, EPA's recent PBO risk assessment fails to look at the synergist in conjunction with the active ingredient. EPA's risk assessment misses the point, says Paul. "An environmental evaluation needs to know how these things work together. We know there is a synergistic effect on target species. This alone suggests the need to evaluate effects of a formulation on nontarget species," he says. In the case of POEA, Monsanto disputes the concentrations and conditions Relyea used in his experiments. However, at least four other papers dating back to 1988 point the finger of blame at POEA (Lancet 1988, 1, 299; Arch. Environ. Contam. Toxicol. 1999, 36, 193-199; Environ. Pollut. 2001, 114, 195-205; Chemosphere 2003, 52, 1189-1197.) A fifth, more recent paper reports that tadpoles exposed in the lab to POEA concentrations common in the environment (0.6 milligrams per liter [mg/L] and 1.8 mg/L) for 42 days, which is the estimated aquatic half-life of the surfactant, exhibited delayed metamorphosis and developmental abnormalities (Environ. Toxicol. Chem. 2004, 23, 1928-1938) Steve Bradbury, director of EPA's Office of Pesticide Programs Environmental Fate and Effects Division, acknowledges that some inerts, including POEA, may have toxicological profiles that cause concern. However, usage restrictions for products containing POEA clearly state on the label that it should not be applied directly to water. Label restrictions miss the point, say Relyea and others, who note that chemicals in the environment often stray from their intended locations. For example, when U.S. and Canadian foresters spray glyphosate herbicides from helicopters and planes onto forest to eliminate plants after clear cutting, mist inevitably drifts off target. Frogs living and breeding in wetlands and small ponds in or near forests are unintentionally exposed to formulations containing POEA, these scientists note. A study of aerial applications of Roundup found that small wetlands can receive up to 1.9 mg of acid equivalents per liter (Environ. Toxicol. Chem. 2004, 23, 843-849). Several environmental risk assessments conducted for glyphosate herbicides did not include information from Relyea's work and more recent studies (J. Toxicol. Environ. Health, Part B 2003, 6, 289-324; Glyphosate: Human Health and Ecological Risk Assessment Final Report, SERA TR 02-43-09-04a, U.S. Department of Agriculture Forest Service, 2003). These assessments acknowledge the more potent aquatic toxicity of POEA and the lack of monitoring, sublethal effects, and environmental occurrence data. However, they conclude that the risk of adverse effects in the aquatic environment is generally small. Nevertheless, an Australian governmental review in 1996 found that the POEA in Roundup presented a toxic risk to tadpoles and frogs in shallow water, where dilution doesn't occur. "The use of the POEA surfactant is an anachronism in light of its well-documented toxicity and the availability of substitute surfactants with demonstrated lower toxicities," argues biologist Reinier Mann, who at the time worked in Australia and is now at the Universidade de Aveiro (Portugal). "We know [POEA is] toxic," states Canadian Wildlife Service toxicologist Bruce Pauli, who is the corresponding author of the 42- day exposure study. "We hope there's not enough in the water to cause a problem." But at a time when amphibian populations are declining dramatically for unknown reasons, he asks: "Is that really protecting the environment?"