Genotoxic Risks Resulting from the Trihalomethanes Contained in Drinking Water

1. This contribution is dedicated to the memory of M.Sc. Lenka JESONKOVA-PAVLICA, Ph.D., who I led during doctoral studies,and whoparticipated in data acquisition.She tragically died at birth on 25 April 2017 at the age of 29. Genotoxic Risks Resulting from the Trihalomethanes Contained in Drinking Water Prepared by: Frantisek BOZEK, Lenka JESONKOVA-PAVLICA†, Jiri KONECNY, Magdalena NAPLAVOVA and Michal MACKO T. Bata University in Zlin, Faculty of Logistics and Crisis Management, Department of Crisis Management, Student Square 1532, 686 01 UherskeHradiste Contact: e-mail:frantisekbozek@seznam,cz, phone.: +420 604 181 848

2. Introduction • Sanitary treatment of drinking water through disinfection may produce disinfection by-products (DBPs), which have negative impacts on the quality of drinking water. • Such DBPs may occur due to the interaction of oxidation agents with organic substances, which are naturally present also in ground waters. • The most significant DBPs identified in water are halogenacetic acids, halogenacetonitriles, chloral hydrate (2,2,2-trichloro-1,1-ethanediol), chlorophenols, bromates chlorine cyan, trihalogenmethanes (THMs). • THMs, including chloroform (CHCl3), bromodichloromethane (CHBrCl2), dibromochloromethane (CHBr2Cl) and bromoform (CHBr3), are the dominant products of the reaction of disinfection means on chlorine base with organic precursors.

3. Introduction • THMs show hepatotoxic and nephrotoxic effects. • Carcinogenic, mutagenic, teratogenic and embryotoxic effects are not excluded either. • Therefore their contents in water have to be carefully monitored and in case of higher concentrations both non-carcinogenic and genotoxic risks have to be assessed for the exposed population.

4. Applied Methods and Devices • The concentration of THMs in drinking water was determined by the liquid-gas extraction technology with the help of the TriPlus static headspace dosing device and the Trace GC Ultra gas chromatograph with the Trace DSQ mass detector, produced byThermoelectron Corporation. • The limit of determination for individual THMs was 0.1 g dm-3. • The sampling of drinking water was carried out in compliance with standards.

5. Applied Methods and Devices • The assessment ofgenotoxic risks was carried out in compliance with the valid Czech guidelines and instructions which are based on the method proposed by the U.S. EPA. • The dimensionless quantity of individual excess cancer risk ECR showing the increase over the general average was used for the genotoxic risk description: (1) • The individual values of ECR EP,A,S for the assessed exposure pathways (EP), age periods (A) and contaminants (S) were calculated by use of relation (1), where ADDEP,A,S[g kg-1 day-1] represents the corresponding average daily dose, and CSFEP,S [kg day µg-1] is the cancer slope factor for the assessed exposure pathway EP and a contaminant S. • .

6. Applied Methods and Devices • The risk ECREP, A,S was assessed for three consequential age categories A: new-borns, children, and adults. As pollutants S were considered CHCl3, CHBr2Cl, CHBrCl2 and CHBr3. • CFSs were taken from IRIS of U.S EPA and RAIS of ORNL. Individual exposure factors were taken from same databases and from the Czech methodology. • ADDEP,A,S for pathways EP, age periods A and contaminants S were calculated according following equations. ADDING = cw,S × IRING,A × bA × EFA × EDA × BWA-1× ATA-1(2) ADDDC =cw,S × SAA × Kp,A,S × ETA × EFA × EDA × Cf × BW A-1 × ATA-1(3) ADDINH = ca,S × IRINH,A × ETA × EFA × EDA × BWA-1 × ATA-1(4) ca,S = cw,S × f × Q × tA × V -1 × 2-1 (5)

7. Applied Methods and Devices Provided that individual exposure pathwaysEP and pollutantsS have additive effects, the summary ECRA for age category A may be defined by the following formula (6) S=nEP= m ECR A = ΣΣECRA, S, EP(6) S = 1 EP = 1 where ECR A, S, EP representsthe dimensionless quantity of individual excess cancer risk showing the increase over the general average for particular age period (A), contaminant (S) and exposure pathway (EP), m is the number of exposure pathways and n the number of contaminants.

8. Applied Methods and Devices The final value of ELCR was calculated as asimple sum ELCRSUM through the selected age groups A according to theequation(7), or by the weighing average ELCRWEIGHTaccording to the relation (8), which considers the length of exposure tA[year] in each of age groups. Symbol t is the sum of exposure duration of all considered age subpopulations and q means the number of age categories. (7) (8)

9. Limits and characteristics of ELCR • There is a consensus in the world that the acceptable limit for the individual genotoxic risk is ELCE 10-6. • If ELCR (10-6; 10-4, the genotoxic risk is tolerable. • If ELCR 10-4, the risk is unacceptable. In this case and it is necessary either to implement corrective measures immediately, or to stop the particular activity.

10. Outcomes and Discussion Tab. 1 The concentrations of THMs (neg. means the absence of detector response)

11. Outcomes and Discussion Tab. 2 The cancer slope factors CSFS,EP

12. Outcomes and Discussion The following principles were followed during determining the exposure scenarios of carcinogenic effects of THMs and the calculation of average daily doses ADDEP,A,S: • Due to the uncertainty of 35% of determinated individual THMs, their median concentrations used for ADDEP,A calculation were increased just above this value; • For the calculation of inhalation exposures it was not feasible to express numerically the values of individual THMs backgrounds in the „indoor“ air, where THMs are released during an arbitrary manipulation with water with the free water level being in contact with the air. In order to partially compensate such an effect, the exchange of air was not considered during the time the persons stayed in the bathroom;

13. Outcomes and Discussion • As the cancer slope factor CSFDC,S was absent and the CSFINH,S was known, the excess lifetime cancer risk caused by dermal contact was considered as being of one third of risk caused by inhalation pathway, i.e. ECRINH,A,S = 3 x ECRDC,A,S, which is in compliance with the recommendation of the U.S EPA; • As the cancer slope factors both for inhalation CSFINH,S and dermal contact CSFDC,S were absent, the cancer risk caused by both inhalation and dermal contact was considered equal to the cancer risk caused by ingestion, i.e. ECRINH+DC,A,S = ECRING,A,S according to the recommendation of the U.S EPA, as well.

14. Outcomes and Discussion Tab. 3 Values of average daily doses ADDEP,S, excess cancer risks ECREP,S,ECREP,ECRS and summary risks ECREP,S fornew-borns up to one year ND = non-dimensional value

15. Outcomes and Discussion Tab. 4 Values of average daily doses ADDEP,S, excess cancer risks ECREP,S,ECREP,ECRS and summary risks ECREP,S forchildren 1-8 years ND = non-dimensional value

16. Outcomes and Discussion Tab. 5Values of average daily doses ADDEP,S, excess cancer risks ECREP,S,ECREP,ECRS and summary risks ECREP,S for adults 18-70 years ND = non-dimensional value

17. Outcomes and Discussion Simple solar water disinfection ► The final value of excess lifetime cancer risk ELCRSUM respecively ELCRWEIGGT were calculated according to equation (7) respectively (8) and their values are presented below: 7.3110-5 (7) 8.9110-6(8)

18. Uncertainties • Data on the concentrations of THMs are objective, with the level of uncertainty 35%. • The selection of water sampling site affects the values of ELCRSUM and ELCRWEIGHT by more than one order within the assessed region as it results from the measured concentrations of THMs. It is clear from the Tab. 1 that e.g. the summary concentration of THMs at the sampling point D is almost 50 times lower in comparison with the same datum at the sampling point B, which was selected for the risk assessment. This fact represents maybe the most serious uncertainty and more significantly increases the assessed values of APCRSUM and APCRWEIGH, because it cannot be expected that all inhabitants of the region will be exposed to the drinking water the most contaminated by THMs.

19. Uncertainties • The exposure scenarios, developed for the assessed age categories, try to model the behaviour of people during ingestion and consumption of drinking water. There is not elaborated a standardized model for new-borns and children in the Czech methodical instructions. A number of exposure factors, especially for these age categories, had to be either adopted from US EPA or estimated. • The process of ingestion and consumption of drinking water is highly variable and is the function of many factors, such as sex, education, social and cultural environment, household equipment, habits, etc. which bring further uncertainties into the construction of exposure scenarios. • The validity of CSFEP,S, taken from databases, is assessed by the institutions themselves as „medium“.

20. Uncertainties • The calculations of ADDEP,A,S are based on the assumption of full absorption of contaminants in the human organism, which is not very likely to happen in practice. This fact also increases the assessed values of ELCRSUM and ELCRWEIGHT . • The inhalation/dermal ratio of THMs intake was pINH/DC = 3 for the needs of risk assessment. It was based on the experiments with CHCl3, although there can be found pINH/DC1; 3 in the literature. The choice of pINH/DC does not significantly affect the assessment of genotoxic risk expressed in the form of ELCRSUM and ELCRWEIGHT because pINH/DC = 3 was applied solely to CHBr3, the concentration of which in the samples of drinking water was much lower compared to other THMs.

21. Uncertainties • There were not found CSFINHfor inhalation nor CSFDC for absorption in case of CHBrCl2 and CHBr2Cl in the available materials. Therefore the intake of joint inhalation and dermal pathways was considered as equivalent to the intake through ingestion, which was in compliance with the recommendation of the US EPA. However, the above mentioned substitution may increase the value of ADDINH +ADDDC by one order especially among new-borns up to the age of one. • The level of ELCR over the general average is dependent on the applied option of numerical quantification of ELCR, as it is demonstrated on the acquired values of ELCRSUM and ELCRWEIGHT .

22. Uncertainties • The degree of genotoxic risk ELCRSUM and ELCRWEIGHT will also be the function of dividing the exposure into the assessed age categories A, the selection of which will affect the values . • The assumption of the additive effect of THMs is another factor increasing the uncertainty of the assessment of ELCRSUM and ELCRWEIGHT, because the mutual interaction of THMs may show not only synergic, but also antagonistic effects. • The interaction of THMs with other compounds present in the analyzed samples of drinking water was not considered either. It also reduces the validity of acquired outcomes.

23. Conclusions Tab. 6Genotoxic risks resulting from the consumption of drinking water containing trihalogenmethanes (9) (10) APCRSUM and APCRWEIGHT mean adequate annual population cancer risk and N = 4105 number of inhabitants in the region.

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