Inactivation of antineoplastics in clinical wastewater by electrolysis
Introduction
Wastewater from clinical institutions contains possibly hazardous substances, such as antineoplastics, disinfectants and antibiotics. Some of the drugs, including antineoplastics, have been classified by the International Agency for Research on Cancer (IARC) as human carcinogens, probable human carcinogens and possible carcinogens (IARC, 1994). Many antineoplastics were reported to be carcinogenic (Haddow et al., 1948; Taylor and Wade, 1984) teratogenic (Hemminki et al., 1985; Hoffman, 1986), and mutagenic (Levin et al., 1982; Beauchamp et al., 1992; NIH, 1999), and may affect directly or indirectly human health and the natural ecological system (Vaccari et al., 1984; Richardson and Bowron, 1985; Daughton and Ternes, 1999). Since the substances are considered to be possible causes of serious genetic problems in the future, they should not be released to the environment without eliminating or decreasing their toxicity.
In many cases, clinical wastewater is treated using activated sludge or discharged into the sewage system after dilution with domestic wastewater (Kawabata, 1997). Some substances in the wastewater may induce the emergence of mutant microorganisms in the activated sludge, and also substances in diluted wastewater may induce the mutation of environmental microorganisms as mentioned by Kümmerer (2001). In industrial factories producing toxic or mutagenic medicines, wastewater is concentrated and incinerated at a high temperature. The incineration of clinical wastewater requires an evaporator or a concentrator of wastewater to increase the concentration of organic matter and obtain a sufficient calorific power for self-combustion. The concentrated wastewater is incinerated with other wastewater in a high-temperature incinerator (Kinoshita, 1989). Such facilities and process increase the cost of treatment of clinical wastewater. Moreover, a high-temperature incinerator requires a high energy and generates carbon dioxide. Although incineration can completely eliminate the toxicity of substances, it is not practical in a clinical setting.
IARC recommends three simple methods using sodium hypochlorite, hydrogen peroxide and Fenton reagent in a clinical setting. Castegnaro et al. (1997) evaluated the degradation of antineoplastics, and concluded that 5.25% sodium hypochlorite treatment is an efficient reagent for the chemical degradation of antineoplastics. Sodium hypochlorite is available in any clinical institutes; however, a stable treatment is not easy because of different conditions, such as temperature and the stability of sodium hypochlorite stock solution.
Recently, electrolysis has mostly been studied in terms of its application to sterilization and disinfection, as electrolyzed products contain hypochlorite (Morita et al., 2000; Kiura et al., 2002; Nakajima et al., 2004). Since the electrolysis of sodium chloride solution generates hypochlorite, antineoplastics in wastewater may be inactivated by electrolysis.
In this study, we electrolyzed epirubicin hydrochloride (EH) solution, which is widely used in clinical settings in Japan in the treatment of leukemia, malignant lymphoma, mammary cancer, ovarian cancer, gastric cancer, hepatoma, and urinary cancers, to examine whether electrolysis eliminates the biological activity and toxicity of this chemical, and determined the quantity of active ingredients by HPLC. Other antineoplastic drugs and a mixture of antineoplastics were also electrolyzed under optimal conditions determined for EH and their biological activity and toxicity were bioassayed.
Section snippets
Chemicals
Commercially available vials of EH (Pharmacia Japan Co., Tokyo, Japan), irinotecan hydrochloride (Daiichi Pharmaceuticals Co., Tokyo, Japan), methotrexate (Wyeth Japan, Tokyo, Japan) and cisplatin (Nippon Kayaku Co., Tokyo, Japan) were purchased from Kuraya Sanseido Inc., vincristine sulfate (Eli Lilly Japan K.K., Kobe, Japan) from Suzuken Co., Ltd., mitomycin C (Kyowa Hakko Kogyo Co., Tokyo, Japan), and paclitaxel (Bristol Pharmaceuticals Y.K., Tokyo, Japan) from Aswell Inc. The solutions of
Antibacterial activity and cytotoxicity
To examine whether electrolysis eliminates the cytotoxicity of EH against prokaryote, the MIC of electrolyzed EH against S. aureus was measured. MIC increased exponentially (y = 1.56e1.39x) in a time-dependent manner (Fig. 1a). After 4 h of electrolysis, the MIC of the sample was more than the detection limit. The increase in MIC indicated that antibacterial activity was eliminated by electrolysis. The above findings indicated that electrolysis decreased the antibacterial activity of EH to less
Discussion
In this study, we demonstrated that electrolysis degrades EH and eliminates its cytotoxicity and mutagenicity. Although small amounts of decomposition products were generated during electrolysis, these products did not have cytotoxicity and mutagenicity against bacterial and human cells. The degradation and elimination were also noted in the electrolysis of a mixture of antineoplastics. The degradation by electrolysis generates active oxidants such as hypochlorite. Although we could not clarify
Acknowledgment
This study was performed under the University-Industry Collaboration Contract between Osaka Medical College and Sanyo Electric Company, and was supported by a Grant for Industry-University Collaborative Study from the Ministry of Education, Culture, Sports, Science and Technology, Japan.
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