A toxicological study on photo-degradation products of environmental ibuprofen: Ecological and human health implications.

Increasing quantities of pharmaceutical waste in the environment have disrupted the balance of ecosystems, and may have subsequent effects on human health. Although a handful of previous studies have shown the impacts of pharmaceutically active compounds on the environment, the toxicological effects of their degradation products remain largely unknown. In the current study, the photo-degradation products of environmental ibuprofen were assessed for both ecotoxicological and human health effects using a series of in vitro assays. Here, six of the major degradation products are synthesized with high purity (>98%) and characterized with 1HNMR, 13CNMR, FT-IR and HRMS. To evaluate human health effects, three gut microbiota species, Lactobacillus acidophilus, Enterococcus faecalis and Escherichia coli, and two human cell lines, HEK293T and HepG2, are exposed to various concentrations of ibuprofen and its degradation products. On L. acidophilus, the ibuprofen degradation product (±)-(2R,3R)-2-(4-isobutylphenyl)-5-methylhexan-3-ol shows a greater toxic effect while ibuprofen enhances its growth at lower concentrations. At higher concentrations, ibuprofen shows at least a 2-fold higher toxicity compared to that of its degradation products. However, E. faecalis shows little or no effect upon exposure to these compounds. An induction of the SOS response in E. coli is observed but limited to only ibuprofen and 4-acetylbenzoic acid. In human cell line studies, survival of both HEK293T and HepG2 cell lines is profoundly impaired by the photo-degradation products of (±)- (2R,3R)-2-(4-isobutylphenyl)-5-methylhexan-3-ol, (±)-(2R,3S)-2-(4-isobutylphenyl)-5-methylhexan-3-ol, and (±)-1-(4-(1-hydroxy-2methylpropyl)phenyl)ethan-1-one. In this work, the bioluminescence bacterium, Aliivibrio fischeri, is used as a model to assess environmental impact. Both ibuprofen and its degradation products inhibit the growth of this gram-negative bacteria with the primary compound showing the most significant impact. Overall, our results highlight that some of the degradation products of ibuprofen can be more toxic to human kidney cell line and liver cell line than the parent compound while ibuprofen can be more toxic to human gut microbiota and A. fischeri than ibuprofen degradation products.

Fate, Transformation, and Toxicological Impacts of Pharmaceutical and Personal Care Products in Surface Waters.

With the growth of the human population, a greater quantity of pharmaceutical and personal care products (PPCPs) have been released into the environment. Although research has addressed the levels and the impact of PPCPs in the environment, the fate of these compounds in surface waters is neither well known nor characterized. In the environment, PPCPs can undergo various transformations that are critically dependent on environmental factors such as solar radiation and the presence of soil particles. Given that the degradation products of PPCPs are poorly characterized, these "secondary residues" can be a significant environmental health hazard due to their drastically different toxicologic effects when compared with the parent compounds. To better understand the fate of PPCPs, we studied the degradation of selected PPCPs, including ibuprofen and clofibric acid, in aqueous solutions that contained kaolinite clay and were irradiated with a solar simulator. The most abundant degradation products were identified and assessed for their toxicologic impact on selected microorganisms. The degraded mixtures showed lower toxicity than the starting compounds; however, as these degradation products are capable of further transformation and interaction with other PPCPs in natural waters, our work highlights the importance of additionally characterizing the PPCP degradation products.

Abiotic degradation and environmental toxicity of ibuprofen: Roles of mineral particles and solar radiation.

The growing medical and personal needs of human populations have escalated release of pharmaceuticals and personal care products into our natural environment. This work investigates abiotic degradation pathways of a particular PPCP, ibuprofen, in the presence of a major mineral component of soil (kaolinite clay), as well as the health effects of the primary compound and its degradation products. Results from these studies showed that the rate and extent of ibuprofen degradation is greatly influenced by the presence of clay particles and solar radiation. In the absence of solar radiation, the dominant reaction mechanism was observed to be the adsorption of ibuprofen onto clay surface where surface silanol groups play a key role. In contrast, under solar radiation and in the presence of clay particles, ibuprofen breaks down to several fractions. The decay rates were at least 6-fold higher for irradiated samples compared to those of dark conditions. Toxicity of primary ibuprofen and its secondary residues were tested on three microorganisms: Bacillus megaterium, Pseudoaltermonas atlantica; and algae from the Chlorella genus. The results from the biological assays show that primary PPCP is more toxic than the mixture of secondary products. Overall, however, biological assays carried out using only 4-acetylbenzoic acid, the most abundant secondary product, show a higher toxic effect on algae compared to its parent compound.