Toxicity of polar metabolites associated with petroleum hydrocarbon biodegradation in groundwater.

The recent study by O’Reilly et al. [1] describing the identification of 197 esters likely related to the biodegradation of petroleum hydrocarbons in 61 groundwater samples from 10 fuel release sites in California lacks evidence that these compounds have a “low toxicological profile,” which is the argument used by the authors to promote the routine use of silica gel cleanup. The detection ofmore esters than unique carboxylic acids at these sites is interesting because esters are thought to become easily hydrolyzed to acids and alcohols in the environment, and the presence of petroleum-related acids at spill sites has been well documented in the past [2,3]. Living organisms generate esters for many purposes including the transport and excretion of xenobiotics. Given the complexity of microbial consortia required for hydrocarbon degradation, it is therefore not entirely unexpected to see a variety of esters, including potentially toxic dead-end metabolites, at fuel release sites. While the study identifies a large number of novel putative petroleum hydrocarbon metabolites, the authors’ sweeping claims regarding their toxicity are not supported. Unlike a cited reference on petroleum biodegradation [4], the authors do not report any toxicity studies. No literature search was performed on any of the 197 compounds identified. Instead, the authors claim in the last paragraph that they have determined in a previous study [5] that esters in general “have a low potential for human toxicity.” In that study, the authors assume that the toxicity of all (petroleum-related) acids and esters is similar to that of 14 acids culled from the literature and unrelated to any compounds identified at fuel release sites. Esters are not considered separately. The study referred to [5] also presents an incomplete description of a qualitative ranking scheme (low, low-to-moderate, or moderate) that is similar to ranking schemes that have been used occasionally to classify certain types of chemicals for commercial trade purposes. Such schemes, however, were not intended for making general statements about the toxicity of all acids or esters, for example, or about environmental contaminants. The presence or absence of a specific functional group is by itself a poor predictor of toxicity, especially given the variety of possible structures and the fact that biological effects such as toxicity tend to be exquisitely sensitive to small structural variations. The claim that all esters have low potential for human toxicity appears overly broad given the sheer number of compounds and the fact that most have not been evaluated for toxic effects. A closer inspection of the chemical structures presented in Figure 1 of the subject study [1] results in a more nuanced perspective regarding the spectrum of potential toxicities of the esters identified at petroleum release sites. Only the first 2 of the 18 structures depicted in Figure 1 are simple aliphatic monoesters without branches, double bonds, or additional functional groups. Some feature branched structures. Ester 5 is intriguing because it contains the same tertiary butyl alcoholderived group as methyl tertiary butyl ether. Esters 9, 11, 16, 17, and 18 feature aromatic rings as part of the acid and ester 10 as part of the alcohol moiety. Cycloalkanes are present in the acid moiety of esters 6, 7, and 8, and the alcohol moiety of esters 11, 12, 14, and 18. Many of the compounds in Figure 1 appear to be derivatives of naphthenic acids, a term used for complex mixtures of petroleum-related carboxylic acids containing characteristic cycloaliphatic as well as varying amounts of (acyclic) aliphatic and aromatic side chains. Naphthenic acids, constituents of crude and biodegrading oil, have been the subject of many studies in which evidence for toxic effects in humans, and especially in aquatic environments, were found [6,7]. This is a concern where contaminated groundwater is discharged to surface water bodies. Of particular interest regarding adverse effects in humans are esters 16 and 17 in the bottom row of Figure 1. They are labeled 1,2-benzenedicarboxylic acid, mono(2-ethylhexyl)ester, and 1,2-benzenedicarboxylic acid, bis (2-methylpropyl)ester but they are better known as mono(2-ethylhexyl) phthalate (MEHP) and diisobutylphthalate, respectively. Mono(2-ethylhexyl) phthalate has been linked to a number of potential adverse health effects in humans, which range from endocrine changes to oxidative stress and deoxyribonucleic acid (DNA) damage [8–12]. The active metabolite responsible for many of the toxic effects of di(2-ethylhexyl)phthalate (DEHP) is MEHP. Di(2ethylhexyl)phthalate is the most toxic of the phthalate esters currently listed in the US Environmental Protection Agency Regional Screening levels [13]. Two more phthalates are identified in the Supplemental Data to the subject study, diisooctyl phthalate and monobutyl phthalate. The latter can be a metabolic product of the better known dibutyl or benzylbutyl phthalates. The list of phthalate esters investigated for toxic effects in human and environmental receptors keeps growing. Thus, the discovery of phthalates at petroleum sites is worth noting. The number of phthalates known to have endocrine effects (which can occur at very low concentrations) is also increasing. Therefore, even if individual concentrations were found to be low, cumulative effects as a result of the presence of multiple bioactive phthalates, and possibly other endocrine disruptors derived from petroleum through biodegradation, may cause significant adverse health outcomes apart from the parent petroleum compounds. Phthalates and other petroleum metabolites may cumulatively cause oxidative stress or raise the risk of cancer and other diseases by interacting with multiple biological targets in one or more pathways. Biodegrading petroleum sites may generate a unique spectrum of phthalates that could adversely impact human health and the environment. Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/etc.3463 Environmental Toxicology and Chemistry, Vol. 35, No. 8, pp. 1900–1901, 2016 # 2016 SETAC Printed in the USA