Cancer risk analysis and assessment of trihalomethanes in

drinking water of Taiwan

Yir-Yarn Yeh*, Han-Keng Lee** , Wei-Ming Chen** and Yi-Jie Huang**
* Graduate Institute of Civil and Hydraulic Engineering, 100, Wnehwa Road, Seatwen, Taichung, Taiwan,
407, ROC (E-mail:yyyeh@fcu.edu.tw)
** Department of Water Resource Engineering, 100, Wnehwa Road, Seatwen, Taichung, Taiwan, 407, ROC
(E-mail: hklee@fcu.edu.tw, r21511@hotmail.com, jammy620@hotmail.com)
Abstract
All of the data collection is supported from Taiwan Water Corporation (TWC) since 1998 to 2002 of Taiwan
regions. Utilization the statistical analysis and Monte Carlo Simulation (MCS) to estimate the cancer risk
analysis and assessment.
Performed by the multistage type of Benchmark model, it can evaluate the dose-response assessment.
Consequence exhibited in the 95% confidence level, the Benchmark dose (BMD) and the quantity of
Lower-bound confidence limit of the BMD (BMDL) of TCM are 1.69 and 1.15 mg (Kg-day)-1,
dibromochloromethane (DBCM) are 1.88 and 1.20 mg (Kg-day)-1, dichloromethane (DCBM) are 2.28 and
1.35 mg (Kg-day)-1, and TBM are 17.6 and 10.3 mg (Kg-day)-1, respectively. Compared the exposure with the
reaction dose concentration of THMs species in drinking water, its a rather lower probability of cancer risk.
In the exposure assessment calculated by MCS, consequence exhibited the principal pathway is inhalation, and
the next is ingestion and dermal intake pathways. The quantity of average risk in male and female are 3.1410-5
~1.0410-4 and 3.6410-5 ~1.1610-4 in northern, 9.2510-6 ~7.2510-5 and 4.0410-6 ~8.4010-5 in middle,
1.1410-4 ~4.0710-4 and 1.3310-4 ~4.6710-4 in southern, and 6.0710-5 and 7.0910-5 in external island,
respectively.
Keywords
DBPs, Monte Carlo Simulation, Multistage of Benchmark model, BMD, Sensitive Analysis.

INTRODUCTION
Chlorination has been the major economical and effective drinking water disinfection strategy from
microorganisms. This disinfection process may induce serious waterborne infectious diseases
dangerous to public health. Research consequence of Rook, Bellar and Lichtenberg (1974) exhibited
that DBPs were produced in the disinfection process. DBPs are defined as hazardous materials with
carcinogenic risk. Nowadays, such disinfection process is most adopted chemical disinfectant in
drinking water treatment commonly (Houston, 1913; Yang et al., 1998 and Hsu et al., 2001).
Directly, the principal sources of drinking water in Taiwan are from rivers, approximately 59.3%,
groundwater - 21.7% and reservoirs - 19.0% respectively. (Hsu et al., 2001). However, its
approximated that 36.0% of rivers are polluted. Providing safe drinking water and decreasing the
carcinogenic risk are important because the drinking water population supply rate has reached
88.68% (18,497,289 persons, 2004, TWC. http://www.water.gov.tw).
However, animal and epidemiology study evaluations have shown that developmental toxicity and
adverse effects are the main potential risks to humans. The result from animal studies demonstrated
evidence of liver, kidney, intestinal tumor genesis, urinary bladder, rectum and colon cancer (Morris,
1995; Doyle et al., 1997; Cantor et al., 1998) and some associated effects of intrauterine growth and
retardation (Kramer et al., 1992). Low birth weight, small for gestational age, central nervous system
defects, oral cleft defects and cardiac defects (Bove et al., 1995), retarded fetal growth (Gallagher et
al., 1998) and spontaneous abortion (Waller et al., 1998) that are caused by disinfected water.
For many drinking water DBPs, the potential for exposure and uptake occurs by ingestion but also
through dermal absorption or inhalation (Lee et al., 2004). Since 1990, scientists proposed that
inhalation and dermal absorption were considered in the risk assessment of drinking water (Jo et al.,
1990; Maxwell et al., 1991; Weisel and Jo, 1996; Weisel et al., 1999; Lin and Hoang, 2000).
The risk assessment paradigm was developed by the US National Research Council (NRC) in 1983.

Evaluated procedures of framework contained hazard identification, dose-response assessment,

exposure assessment and risk characterization, mainly. The purpose of this study conferred the risk
assessment to process the derived THMs species in the drinking water of Taiwan. In terms of
increasing the THM species concentration may increase the carcinogenic probability progressively.
This may a good topic for analysis in risk management.
METHODS
THMs species data in Taiwan since 1998~2002
This study divided the geographical distribution of Taiwan into five parts (northern, midland,
southern, eastern and external islands). From 1998 to 2002, 4 940 water quality data included
temperature, pH and THMs species obtained from the annual TWC subscriber drinking water
reports.
Cancer risk analysis and assessment
Hazard identification of THMs species
USEPA has developed a scheme that contains two broad categories of sufficient and insufficient
evidence in Table 1. Hossein (1995) defined THM species as TCM, BDCM, DBCM and TBM.
Animal and epidemiology studies exhibited THMs species by considered weight of evidence in EPA
reports on cancer guideline descriptions about Group B2 as TCM, BDCM, DBCM, respectively and
Group C is TBM (USEPA, 1999).
Dose-response assessment
Cancer risk analysis and assessment utilized the scientific method to qualitatively measure the
hazardous materials humans are exposed to in the environment (NRC, 1983). Specially, the purpose
of the assessment developed for the risk management ensures the safety and offers procedures to
control the quality of drinking water.
In the dose-response assessment step, the goal determined the relationships between the route, dose,
frequency and duration of exposure conditions and the health that effect chemical hazards.
Additionally, apply the uncertainty or safety factors and mathematical model may an approach by
USEPA.
Benchmark model (USEPA, http://www.epa.gov/ncea, 2003) supported the assessment tool focused
on the low-dose in the animal experiment that may cause an observed adverse influence. Generally,
the adverse effects included reproductive, developmental toxicity or mortality phenomenon etc.
Exposure assessment
Exposure is defined as human contact with THM species through different pathways. Referring to
the exposure factor data handbook (USEPA, 1997), USEPA risk assessment guidance for superfund
Volume-Human Health Evaluation Manual (USEPA, 1989), Wang et al. (2000) and Risk
Assessment Information System (RAIS, 2003) assumed the pathways to reasonable maximum
exposure (RME) to THM species as ingestion, inhalation and dermal intake, evaluated based on
chronic daily intake (CDI).
Moreover, the study assumed the behaviors of drinking water, take a shower, and skin contact
in the shower represent the exposure pathways of ingestion, inhalation and dermal intake
simplistically (Dan et al., 2003). The mathematic model by Little (1992) exhibited THM species
concentration within the air was influenced by many parameters adopted to evaluate the
concentration in the bathroom. All exposure pathway formulas and parameters are displayed in Table
2.
Risk characterization

In this step, the hazardous identification, dose-response and exposure assessment procedures are
summarized and integrated into quantitative and qualitative expressions of the risk level. For
carcinogenic effects, the risk is expressed as the probability that an individual will exhibit
dose-response characteristics. Under the assumption that the slope factor is a constant, the risk related
to the intake pathways in this study directly.
Linear low-dose cancer risk equation Risk=CDI*SF,
Where Risk=a unitless of an individual developing cancer.
CDI=chronic daily intake averaged over 70 years (mg (Kg-day) -1).
SF=slope factor, expressed in mg (Kg-day) -1.
Estimating the risk or hazard potential requires a combination of simultaneous exposures to more
than one pathway and carcinogenic effect, assuming dose additivity. Assuming that there are no
synergistic or antagonistic interactions, the total cancer risk assumes that all carcinogens are equal,
and the slope factors derived from the animal data are given the same weights as factors derived from
the human data.
Total exposure cancer risk=Risk (exposure pathway 1) + Risk (exposure pathway 2)++ Risk
(exposure pathway i)
Table 1. Animal experimental carcinogenic data derived from THMs species.
Chemicals

Data Set

TCM

Moderate or marked fatty cysts in males

plus females

BDCM

B6C3F1 mice, male

DBCM

mouse/B6C3F1, female

TBM

F344/Nrat, female

Data Values
Dose
N
Incidence
(mg/kg/day)
0
27
1
15

15

30

15

13

25

50

50
0

50
46

8
1

25
50
0
50
100

49
50
50
49
50

2
9
6
10
19

0
25
50

50
50
50

0
1
8

Reference

Heywood et al., 1979

NTP, 1987

NTP, 1985

NTP, 1988

IRIS,2003

Uncertainty and sensitivity analysis

There are several types of uncertainty. An important task in risk analysis is to determine what kinds
of uncertainty are likely to affect the MCS finding suggested by USEPA (1997) in processing the
uncertainty and sensitivity analysis. Essentially, MCS involves conducting and comparing repeated
inputs that sample the system parameter distributions. This study utilized @Risk view (version 4.5)
software to execute the data probability distribution and simulate the sensitivity using MCS.
RESULTS AND DISCUSSION
Hazard identification
Annual
reports
from
the
Department
of
Health,
Taiwan
(DOH,
http://www.doh.gov.tw/statistic/index.htm) announced the mean numbers for these cancers, which
were discriminated by location from 1996 to 2000. The investigation results exhibited colon (1 535),

rectum (1 188) and bladder (566) as the main causes of death in the Northern Taiwan region. In
proportion to the total population, the southern region presented a high ratio of these cancers. A
higher cancer risk in exists in the Southern region because of a higher THM species concentration.
Dose-response assessment
This study adopted a multistage type of Benchmark model approved by USEPA (2003) to process the
dose-response assessment. The chronic toxicity and carcinogenic potential of total THMs species at
low dose situation were interpreted. The BMD/BMDL value for the total THMs species calculated
from the Benchmark model from animal data (95% confidence limits and first stage model fit).
Furthermore, the range of BMD/BMDL value in first/second multistage model. Generally, the BMD
values of 1st are higher than 2nd stage, but the BMDL values are similar between 1st and 2nd stage
model. USEPA proposed the standard BMD and BMDL values of TCM is 1.69, 1.15; BDCM is 2.28,
1.35; DBCM is 1.88, 1.20; and BMD is 17.6, 10.3mg/Kg/day respectively.
Exposure assessment
THM species data processed the weighted average method via the regional population and specific
year to acquire the statistical analysis. The MCS method was used to evaluate the CDI dose and
obtain the probability distribution results by performing 1 000 frequency calculations.
Its the MCS consequence exhibited in the ingestion pathway, southern region exist the higher CDI
values, in opposite to female examined higher CDI endured than male (CDI ranges are 1.07
10-4~1.6310-3 and 9.2210-5~1.4210-3 mg (Kg-day) -1 respectively). The variance in body weight
between females and males is the main reason for the CDI ingestion level. Moreover, in the respired
estimated, consequence exhibited in ingestion pathway, external island exist higher CDI values.
Similarly, females exhibited higher levels than males (CDI range is 7.2810-6~1.4210-3mg (Kg-day)
-1
and 4.2910-5~4.9610-3 mg (Kg-day) -1 respectively) because of their shower behavior. This
included the difference between municipal and rural areas and gender. In the estimated skin contact,
the dermal intake pathway was similar to the ingestion pathway. The Southern region exhibited
higher CDI values and females were higher than males (CDI ranges are 2.5510-7~2.9510-5 and 2.42
10-7~2.8110-5mg (Kg-day) -1 respectively). In the contact time during showers, females took longer
showers than males. The Taiwan DOH announced and suggested that showers not exceed 12
minutes, otherwise, the health risk will increase.
Risk characterization
Assumption the cancer risk is CDI multiplication slope factor and total cancer risks include different
exposure pathways. The total cancer risk assessment order was southern, northern, central over the
external island segment. The average value for females was 4.0410-6~4.6710-4 and 9.2510-6~4.07
10-4 for men respectively. Figure 1 exhibited the THM species distribution via different exposure
pathways to estimate the CDI value, risk assessment and contribution percentage simultaneously.
The cancer risk quantitative analysis evaluation for Taiwan (Arc View plot) is shown in Fig.2. It is
shown that the Southern Taiwan region presents a higher risk.
In term of the inhalation pathway distinct revealed the magnificent in the risk assessment of THMs
species, continuous is ingestion and dermal intake pathways respectively. TCM is the main
contribution to the risk assessment in Taiwan (50% approximately), and TBM is predominance in
external island (50% approximately). These factors are attributed to the water quality in Taiwan and
the sea and groundwater contain high bromide concentrations from water pollution.
Sensitivity analysis
The sensitivity analysis processed the 20% extra risk to interpret the effective THM species
parameters, including body weight, intake quantity and exposure duration in formula of exposure

Table 2. References data and formula for exposure assessment.

Parameters
Weight of Population,

Value

Reference

C i Pi
Ptotal

C =

CiConcentration of i region
Pi Population of water supply in the i region
P total Total population of water supply in the i region
Exposure pathway of Ingestion, CDI =

(CW 0.8 IR EF ED)

( AT BW )

Chronic daily intake, CDImg (Kg-day)-1

THMs concentration of drinking water, CW
Intake quantity, IR
Average exposure time, AT
Exposure during, ED
Exposure frequency, EF
Body Weight, BW

2.5(liters day-1)
70(year)365(day/year)
70(year)
365(day year-1)
Male64.8 10(Kg)

Wu,1999
USEPA,1989
USEPA,1989
USEPA,1989
Taiwan DOH
www.doh.gov.tw/statistic/index.htm

Female56.3 9.09(Kg)
100%

Absorptivity of body
Exposure pathway of Inhalation, CDI =

Assumption

(C air VR EF ET ED)
( AT BW )

THMs vapor concentration in the bathroom, Cair

Mean vapor quantity of daily inhalation (adult),
12.3(m3 day-1)
VR
0.032(L min-1)
Flow velocity, QL
Air flow velocity, QGS
50(L min-1)
Volume of bathroom, Vs
6.6
TCM: 0.150
BDCM: 0.087
Henry constant, H
DBCM: 0.032
TBM: 0.022
Transferred coefficient of liquid mass valid
0.019
air/surface area, KOLA
Exposure pathway of Dermal intake, CDI =

Wu, 2003
Wu, 2003
Little,1992
Wu,2003
RAIS, 2003
Little,1992

(CW PC SA EF ET ED)
( AT BW )
TCM: 8.910-3 (cm hr-1)
BDCM: 5.810-3 (cm hr-1)
DBCM: 3.910-3 (cm hr-1)
TBM: 2.610-3 (cm hr-1)
(4BW+7) (BW+90)-1
20(min day-1)

Dermal intake permeable coefficient, PC

Surface area dermal intake contact, SA
Exposure timeET

USEPA,1997
USEPA,1997
MCKone ,1989

Dermal TBM

100%

Dermal DBCM
Dermal BDCM

80%

Dermal TCM
In halation TBM

60%
40%
20%
0%
JL

TP

TY

SC

ML

TC

NT

CH

YL

CY

TN

KC

PD

PH

Dermal TBM
100%

Dermal DBCM

90%

Dermal BDCM

80%

Dermal TCM

70%

In halatio n TBM

60%

In halation DBCM

50%

In halatio n DBCM

In halation BDCM

40%

In halatio n BDCM

In halation TCM

30%

In halatio n TCM

In gestio n TBM

20%

In gestion TBM

In gestio n DBCM

10%

In gestio n BDCM

0%

In gestio n TCM

In gestion DBCM
JL

TP

TY

SC

ML

TC

NT

CH

YL

CY

TN

KC

PD

PH

In gestion BDCM
In gestion TCM

Fig.1. Different contribution percentage of THMs species and exposure pathways in cancer risk
assessment (left is male and right is female).

Fig.2. Quantity of cancer risk assessment of Taiwan (Arc View plot)

assessment. Analysis was performed using the radar plots exhibited in Fig.3. The research regions
displayed a negative correlation consistent with the exposure duration and positive correlation in
body weight dramatically. Furthermore, the TCM concentration is the predominant influence
parameter in Taiwan, whereas the external islands are influenced by the DBCM concentration.
TCM
5
4
3
2
1
0
-1
-2
-3
-4
-5

ET

BDCM

IR

DBCM

BW

TBM

TCM
5
4
3
2
1
0
-1
-2
-3
-4
-5

ET

BDCM

IR

DBCM

BW

TBM

Fig.3. Radar plots for sensitivity analysis in Taiwan area (left) and external island (right)
CONCLUSIONS
This investigation included statistical analysis, epidemiology data and cancer risk analysis and
assessment of THMs species in drinking water in Taiwan. It is more significant to establish an
assessment procedure for the decision-making in policy of drinking water safety predominantly.
Specification the derive conclusions lie above from this study:
(1).The TCM concentration is the major DBP species in the local regions of Taiwan. The external
islands are characterized by TBMs. The ratio of bromide compounds showed an increasing tendency
in the Northern and Southern regions in recent years. This is related to water resources pollution and
groundwater pullulated by seawater.
(2).A Multistage Benchmark model (USEPA, 2004) was utilized for dose-response assessment in
this study to estimate the BMD/BMDL values of THMs species. In terms of lower quantity of
BMD/BMDL showed doses opposite to the cancer risk obviously. The exposure assessment showed
that the inhalation pathway was predominant.. The Southern region presented a high cancer risk. The
temperature factor was the main reason corresponding to previous research. Furthermore, females
presented higher CDI values (intention risk level) than males in Taiwan.
(3). Quantifying the risk factors is important for population and decision-making policy for drinking
water safety. Fortunately, the Benchmark model and MCS @Risk supply the methodology were used
for risk calculation. The standard for the total THMs species in Taiwan was 100ppb presently. We
suggest that the standard be separated using separate TCM, BDCM, DBCM, and TBM standards.

This may establish a control management for individual material to reduce the harmful risk. It
displays the legislation limit values for different counties for DBPs levels.
(4). Consequence of sensitivity analysis exhibited body weight and exposure duration are provided
the influence in cancer risk analysis and assessment predominantly. Besides, TCM and bromide
compounds such as TBM and DBCM have influenced in all regions and external island respectively.
Because many parameters influence the assessment results, considered the multiple assessment
method may reduce uncertainty factors occurred.
(5). A methodology for decision-makers in formulating a procedure considering the economic,
political, and feasible technology to reduce the standard value limits is necessary. An acceptable
policy for safe drinking water and optimum social cost is the next objective of our study.

Acknowledgement
The authors gratefully acknowledge the fund support by National Science Council (NSC) and the
assistance of the Taiwan Water Corporation in this study.
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