A comprehensive review of the environmental impacts and human health risks associated with the occurrence of waste pharmaceuticals in water sources of the United States, and policy implications

The occurrence of waste pharmaceuticals has been identified and well documented in water sources throughout North America and Europe. Many studies have been conducted which identify the occurrence of various pharmaceutical compounds in these waters. This project is an extensive review of the documented evidence of this occurrence published in the scientific literature. This review was performed to determine if this occurrence has a significant impact on the environment and public health. This project and review found that pharmaceuticals such as sex hormone drugs, antibiotic drugs and antineoplastic/cytostatic agents as well as their metabolites have been found to occur in water sources throughout the United States at levels high enough to have noticeable impacts on human health and the environment. It was determined that the primary sources of this occurrence of pharmaceuticals were waste water effluent and solid wastes from sewage treatment plants, pharmaceutical manufacturing plants, healthcare and biomedical research facilities, as well as runoff from veterinary medicine applications (including aquaculture). ^ In addition, current public policies of US governmental agencies such as the Environmental Protection Agency (EPA), Food and Drug Administration (FDA), and Drug Enforcement Agency (DEA) have been evaluated to see if they are doing a sufficient job at controlling this issue. Specific recommendations for developing these EPA, FDA, and DEA policies have been made to mitigate, prevent, or eliminate this issue.^ Other possible interventions such as implementing engineering controls were also evaluated in order to mitigate, prevent and eliminate this issue. These engineering controls include implementing improved current treatment technologies such as the advancement and improvement of waste water treatment processes utilized by conventional sewage treatment and pharmaceutical manufacturing plants. In addition, administrative controls such as the use of “green chemistry” in drug synthesis and design were also explored and evaluated as possible alternatives to mitigate, prevent, or eliminate this issue. Specific recommendations for incorporating these engineering and administrative controls into the applicable EPA, FDA, and DEA policies have also been made.^

Patients' compliance with physician's advice in Costa Rica

The penetration of the western-developed pharmaceutical industry in developing nations has had an impact not only on access to medicines but also on the value attached to medicines and the way they are consumed. People in developing countries have more faith in medicines than in doctors. Medicines constitute a large share of government health expenses but little emphasis has been placed on how medicines are being used. This dissertation includes a discussion on the penetration of pharmaceuticals in the Costa Rican society, a thorough literature review on patients' compliance with medical recommendations (including studies conducted in developed and developing countries, factors affecting adherence, issues involved in measuring compliance, treatment compliance models, and strategies to improve patients' recollection and compliance with medical recommendations), results of a compliance survey conducted in Costa Rica, and a presentation of a compliance model for developing societies.^ The Costa Rican survey includes observations on 505 medical encounters involving 13 general practitioners and 1 pediatrician in 1 urban and 2 rural clinics. Home visits yielded information on patients' adherence to medical recommendations on 404 patients and 988 medicines. The level of patients' adherence in Costa Rica is similar to what has been documented in developed societies but the strategies to improve adherence are different. Costa Ricans are prone to follow the behaviors advertised through the media or recommended by persons they consider knowlegeable in health matters and with whom they can have a personal relationship. Programs to improve adherence to medical regimens should include mass media campaigns, a re-organization of the way drugs are being dispensed, and educating health professionals to communicate and establish meaningful relationships with their patients. ^

Performance enhancement of large industrial wastewater stabilization ponds

A 6-month-long, bench-scale simulation of an industrial wastewater stabilization pond (WSP) system was conducted to evaluate responses to several potential performance-enhancing treatments. The industrial WSP system consists of an anaerobic primary (1ry) WSP treating high-strength wastewater, followed by facultative secondary (2ry) and aerobic tertiary (3ry) WSPs in series treating lower-strength wastewater. The 1ry WSP was simulated with four glass aquaria which were fed with wastewater from the actual WSP system. The treatments examined were phosphorus supplementation (PHOS), phosphorus supplementation with pH control (PHOS+ALK), and phosphorus supplementation with pH control and effluent recycle (PHOS+ALK+RCY). The supplementary phosphorus treatment alone did not yield any significant change versus the CONTROL 1ry model pond. The average carbon to phosphorus ratio of the feed wastewater received from the WSP system was already 100:0.019 (i.e., 2,100 mg/l: 0.4 mg/l). The pH-control treatments (PHOS+ALK and PHOS+ALK+RCY) produced significant results, with 9 to 12 percent more total organic carbon (TOC) removal, 43 percent more volatile organic acid (VOA) generation, 78 percent more 2-ethoxyethanol and 14 percent more bis(2-chloroethyl)ether removal, and from 100- to 10,000-fold increases in bacterial enzyme activity and heterotrophic bacterial numbers. Recycling a 10-percent portion of the effluent yielded less variability for certain physicochemical parameters in the PHOS+ALK+RCY 1ry model pond, but overall there was no statistically-detectable improvement in performance versus no recycle. The 2ry and 3ry WSPs were also simulated in the laboratory to monitor the effect and fate of increased phosphorus loadings, as might occur if supplemental phosphorus were added to the 1ry WSP. Noticeable increases in algal growth were observed at feed phosphorus concentrations of 0.5 mg/l; however, there were no significant changes in the monitored physicochemical parameters. The effluent phosphorus concentrations from both the 2ry and 3ry model ponds did increase notably when feed phosphorus concentrations were increased from 0.5 to 1.0 mg/l. ^

The origin and development of hyperammonemia following exposure to hydrazine in rabbits

Hydrazine $\rm (N\sb2H\sb4),$ an important liquid propellant and derivative chemical for pharmaceuticals and pesticides, produces coma and convulsions sometimes resulting in death. Hyperammonia was found in rabbits exposed to 18 mg/Kg of hydrazine. Results of Part One of this study of rabbits emphasize the importance of acute ammonia toxicity during the first three hours following exposure to hydrazine. At no time during this post exposure period did a significant reduction of hydrazine to ammonia occur. Therefore, the elevated blood ammonia was apparently secondary to the effects of hydrazine on metabolic pathways. Further, the results support the theory of competitive inhibition of ammonia by hydrazine and emphasize the need to monitor plasma ammonia following toxic exposure to hydrazine.^ In Part Two, urea, ammonia, CO$\sb2,$ pH, glucose, sodium, potassium, chloride and creatinine were measured for up to 4 hours following injection of 18 mg/Kg of hydrazine in each of two groups of five rabbits. One group received normal saline and the other group received 5% dextrose and water/normal saline. Hyperammonemia, minimal metabolic acidosis and hyperglycemia without increased urea were found in the rabbits receiving normal saline intravenous infusion and hydrazine injection. Hence, hypoglycemia does not appear to play a role in the development of hyperammonemia. A significant difference in the elevated ammonia levels between the two groups receiving dextrose and water/normal saline and normal saline at 1 hour occurred. There was no significant difference in the elevated ammonia levels seen between the two groups receiving dextrose and water/normal saline and normal saline at 2.5 and 4 hours. Thus at 1 hour the group receiving dextrose was able to utilize excess glucose to detoxify ammonia, while at 2.5 and 4 hours there was no significant difference in the two groups' ability to detoxify ammonia.^ Findings support the theory that hydrazine inhibits the formation of urea resulting in hyperammonemia. Results suggest that hydrazine at 18 mg/Kg, a known hypoglycemic agent, causes serious hyperammonemia without increasing urea production during hyperglycemia. These experiments support a unified theory for the toxic mechanism of action of hydrazine, i.e., the intermediary metabolic effects of hydrazine are brought about by the formation of hydrazones which encumber ATP synthesis and vitamin B$\sb6$ enzymatic reactions. ^

Bench-scale evaluation of the activated sludge process for treatment of a high -strength chemical plant wastewater

A bench-scale treatability study was conducted on a high-strength wastewater from a chemical plant to develop an alternative for the existing waste stabilization pond treatment system. The objective of this study was to determine the treatability of the wastewater by the activated sludge process and, if treatable, to determine appropriate operating conditions, and to evaluate the degradability of bis(2-chloroethyl)ether (Chlorex) and benzene in the activated sludge system. Four 4-L Plexi-glass, complete mixing, continuous flow activated sludge reactors were operated in parallel under different operating conditions over a 6-month period. The operating conditions examined were hydraulic retention time (HRT), sludge retention time (SRT), nutrient supplement, and Chlorex/benzene spikes. Generally the activated sludge system treating high-strength wastewater was stable under large variations of organic loading and operating conditions. At an HRT of 2 days, more than 90% removal efficiency with good sludge settleability was achieved when the organic loading was less than 0.4 g BOD$\sb5$/g MLVSS/d or 0.8 g COD/g MLVSS/d. At least 20 days of SRT was required to maintain steady operation. Phosphorus addition enhanced the performance of the system especially during stressed operation. On the average, removals of benzene and Chlorex were 73-86% and 37-65%, respectively. In addition, the low-strength wastewater was treatable by activated sludge process, showing more than 90% BOD removal at a HRT of 0.5 days. In general, the sludge had poor settling characteristics. The aerated lagoon process treating high-strength wastewater also provided significant organic reduction, but did not produce an acceptable effluent concentration. ^