While some compounds are readily degradable, their continual input causes these compounds to behave like pseudo-persistent pollutants . Direct, acute effects on wildlife are rare due to the low environmental concentrations typical of PPCP/EDCs. However, bio-accumulation of specific compounds in organisms creates the potential for toxic effects in susceptible populations. An example is the drastic decline of the South Asian vulture population, which suffered a species-specific toxicity to diclofenac in scavenged cattle carcasses . A wider concern is sub-acute toxicological effects . For instance, some fragrance compounds in personal products, such as polycyclic musks, as well as some cardiac pharmaceuticals, such as verapamil, have been shown to inhibit multi-drug transporters in cell membranes of aquatic organisms . These transporters are an integral part of an organism’s defense to xenobiotic compounds and their inhibition increases sensitivity to other compounds, like genotoxins . Selective serotonin reuptake inhibitors are a class of antidepressant pharmaceuticals that act by enhancing serotonin signaling in the brain by reducing reuptake of released serotonin. Low levels of SSRIs have been shown to initiate spawning in bi-valves and increase the aggression of subordinate lobsters, which may have subtle effects on ecological communities . Many PPCPs have non-specific toxicity mechanisms that require higher concentrations for acute effects , but EDCs act on specific cellular receptors of the endocrine system, and therefore even at extremely low levels can potentially cause toxicities by disrupting normal endocrine signaling . These compounds have varied modes of action, acting as agonists or antagonists for estrogen, androgen, or other receptors. For instance, bisphenol A and nonylphenol have agonistic effects on the estrogen receptor at cellular concentrations of 22.8 and 2.2 µg/L, respectively, and antagonistic effects on the androgen receptor at 137.0 and 550.9 µg/L, respectively ,vertical growing racks which are levels relevant to concentrations in treated wastewater and relevant to blood serum and urine concentrations in humans .

Exposure to bisphenol A, nonylphenol, and 17β-estradiol have all been shown to increase vitellogenin levels in fish and impact other endpoints like smolt development and survival . The endocrine activity of these and other PPCP/EDCs has contributed to detectable estrogenic and androgenic activity in WWTP effluent , which can cause increased vitellogenin levels and feminization in male fish exposed to effluent . Some of these effects have been observed in the environment , showing that current environmental levels of PPCP/EDCs are high enough to cause adverse effects in wildlife populations. Due to the nature of their environmental input, PPCP/EDCs usually exist as a complex mixture in environmental matrices. There is some evidence that these mixtures act additively, and perhaps synergistically, to elicit biological effects even at low levels . For example, the individual toxicities of the analgesics diclofenac, ibuprofen, naproxen, and acetylsalicylic acid were measured as 68 – 166 mg/L for Daphnia and 72 – 626 mg/L for algae, levels which are considerably higher than the typical ng/L environmental concentrations. However, when the 4 compounds were in a mixture, their toxicities were additive and the EC50 was reached at lower individual concentrations . While these concentrations were still in the low mg/L range, these results have implications for the potential toxicity of environmental matrices that may be contaminated by a multitude of individual PPCP/EDCs . There are also potential human health effects from PPCP/EDC exposures. While present at low levels, PPCP/EDCs are routinely detected in food, packaging, and other materials and the consumption of contaminated agricultural crops would contribute to the total exposure. Exposure to PPCP/EDCs may be detrimental to susceptible age and population groups . The potential impact of EDCs on developing organisms is especially concerning. As an example, cytokine secretion is an important process in human placenta tissue and disruption can lead to pregnancy loss. Nonylphenol was found to affect cytokine secretion in human placenta at cellular concentrations of 0.022 – 220 ng/L . Nonylphenol has been measured in human blood of non-occupational workers at 15.17 µg/L and in human urine at 1.57 µg/L , suggesting that humans are currently exposed to nonylphenol through environmental and other sources at levels sufficiently high to elicit this toxicity.

An emerging concern is the potential health effects of transformation products from the degradation of PPCP/EDCs in WWTP and environmental matrices . For many PPCP/EDCs, their complete fate in the environment and the types of transformation products formed are unknown. Of the limited information, some products of carbamazepine transformation in soil have been identified, which are known to have higher biological activity than the parent compound , a situation that was also known for nonylphenol ethoxylates . The effect on human health from unidentified transformation products with generally unknown behavior and toxicity requires further research. When treated wastewater, bio-solids, or manure is applied to soil, PPCP/EDCs may transfer into the soil compartment . Irrigation with treated wastewater may cause accumulation of PPCP/EDCs to higher levels in soil than in the irrigation water . An example is the 2.34 – 132 and 2.74 – 12.6 fold increase of mass in soils of the stimulant caffeine and the epileptic drug carbamazepine, respectively, as compared to the treated wastewater that was used for irrigation, suggesting accumulation from previous irrigation . bio-solids are applied to land less frequently than irrigation water, due to limitations on nutrient loading and run-off , which allows more time for PPCP/EDC degradation in between input events. Therefore, bio-solids applications typically result in lower levels in soil than in the amendment material .The potential of a compound in soil to be taken up by plants or transport off-site is largely governed by its partitioning between the soil matrix and soil-water. Weak sorption to soil implies enhanced mobility and availability, as in the rapid translocation of the antibiotic sulfachloropyridazine after land application, likely due to its low partitioning coefficient with soil . Adsorption of chemicals to soil is generally related to Kow . For example, in a leaching experiment, the antibiotic olaquindox was mostly recovered in the leachate while the more hydrophobic antibiotic tylosin was retained in the soil column . However, estimating partitioning coefficients from Kow may work well only for neutral PPCP/EDCs,vertical farming in shipping containers where hydrophobic partitioning is the dominant process. With ionizable PPCP/EDCs and in clayey soils, many other factors are likely to be important, including processes such as hydrogen bonding, surface complexation, and cation exchange . In addition, the partitioning behavior of ionizable PPCP/EDCs is highly susceptible to soil pH, as changes in pH may alter the ionic fraction. For instance, acidic chemicals have reduced affinity for clay minerals orsoil organic matter at pH levels above their pKa, resulting in increased availability and mobility .

Partitioning between soil and soil-water is best represented with Kd, which is specific to a compound and soil system and usually determined experimentally . Values can vary widely among soils and among compounds. For example, carbamazepine, diclofenac, and ofloxacin had log Kd values of 1.56, 2.21, and 3.55, respectively, in the same high organic content soil, but in a low organic content soil had values of -0.31, – 0.35, and 3.08, respectively . This specificity hinders the comparison of partitioning behavior between different compounds and different soils across studies. The calculation of a Koc value, by dividing a Kd by the organic fraction in the soil to produce an organic carbon content normalized distribution coefficient, has been used to address this limitation, although Koc values are available only for a limited number of PPCP/EDCs . Table 1.3 lists log Koc values for selected PPCP/EDCs. The persistence of the bio-available fraction of PPCP/EDCs in soil also affects their potential to be taken up by plants. This fraction is difficult to measure, so it is often approximated by the fraction that can be extracted using laboratory protocols . The time required for half of the extractable compound to dissipate is usually described with a half-life or 50% dissipation time , calculated by fitting the percent of a compound that is extractable at several time points to a regression curve or a first-order decay model . Soil half-lives for PPCP/EDCs can vary widely, ranging from hours, in the case of ibuprofen, to years, in the case of fluoxetine, depending on the compound and environmental conditions . One soil dissipation process for PPCP/EDCs involves sorption to the soil matrix and conversion to bound residue that is not recovered by solvent extraction procedures. Formation of bound residues is generally considered a decontamination pathway because the bound fraction is often unavailable for microbial metabolism or plant uptake . This has been shown to reduce or remove the toxicity of pesticides , but similar information is not available for PPCP/EDCs. The formation of bound residue involves several abiotic processes between a compound and the soil matrix, including hydrophobic partitioning, covalent bonding, ligand exchange, migration to micro-sites, and ionic bonding . The relative prevalence of these mechanisms is influenced by the characteristics of the compound and matrix, as well as the duration of compound exposure and concentration . In some cases it has been shown that a small portion of bound residue became available after a change in soil management or by mobilization by microbial metabolism or plant growth, but this may amount to only a few percent of the total residue . Because of the difficulty in assessing the bound fraction of a compound, many studies investigating this process use radio-labeled compounds, but this technique can be costly and is not available to all researchers. Another option is the use of a series of extractions employing progressively harsher solvents, though this approach makes it difficult to relate the various extracted fractions to bio-availability . The potential for PPCP/EDCs to form bound residues has been examined in a few studies. Fent et al. determined that about 80% of 14C-bisphenol A was quickly bound in 4 soils after a 3 d incubation, and the bound fraction persisted throughout a total of 120 d of incubation. Bound residues accounted for 44 – 78% of 14C-diclofenac after 40 d of incubation in a clayey silty soil and a silty sandy soil . Higher soil organic carbon content can enhance the formation of bound residues, which has been shown for diclofenac and carbamazepine . Overall, formation of bound residues is likely an important pathway to decrease the bio-availability of PPCP/EDCs in soil, although more experimental evidence is needed to validate the extent of this process for other PPCP/EDCs.In addition to abiotic processes, there is evidence that microbial activity is important in the formation of bound residues. Nowak et al. showed that 4.5% of ibuprofen was incorporated into fatty acids and amino acids of the soil biomass at 30 d, which decreased to 1.4% by 90 d. This decrease was attributed to population turnover, resulting in the incorporation of non-living fatty acids and amino acids into the soil matrix. Concurrently, at 30 d, 9.4% of ibuprofen was bound to the soil and at 90 d the bound residue fraction increased to 27.9%. Aerobic bio-degradation has been identified as the main route of transformation in soil for veterinary pharmaceuticals . Bacteria can directly use some PPCP/EDCs as growth substrate and can transform others through cometabolism . During cometabolism, the amount of soil organic matter may affect transformation rates since it acts as a substrate for overall microbial activity . Oxygen state affects the rate of microbial transformation . Under aerobic conditions, estrone had a half-life of 0.6 d in soil previously exposed to WWTP effluent, but under anaerobic conditions half-life increased to 6.3 d in the same soil . For triclosan, the effect of oxygen state was even more dramatic; its half-life increased from 5.9 d to 28.8 d. However, the degradation of 17β- estradiol was actually faster in anaerobic soils , showing compound specificity in microbial transformations. Other factors that affect the soil microbial community may also affect transformation rates of xenobiotics, including moisture content, temperature, amendment, and sterilization. For example, transformation of 14C-naproxen was inhibited in soils at cooler temperatures as compared to warmer temperatures . Degradation of naproxen was also reduced in air-dry soils as compared to soils at 15% or 30% water content . Prior exposure to a compound may also potentiate the transformation of a compound by selective enhancement of certain microorganisms .