Deterministic and Probabilistic Health Risk Assessment for Exposure to

Non-Steroidal Anti-Inflammatory Drugs in an Indian River

Ramya Srinivasan, Bokam Rajasekhar, Indumathi M Nambi*

Environmental and Water Resources Engineering Division,

Department of Civil Engineering,
Indian Institute of Technology Madras, Chennai-600036, India
*Corresponding author e-mail: indunambi@iitm.ac.in
First author email id: ramrag2007@gmail.com
Second author email id: rajasekharb.iitm@gmail.com

Supplementary Information

Table S1. Contaminant based risk assessment for different age groups and exposure pathways
Contaminant Children 1 Children 2
Total risk due Oral Dermal Fish Total risk due to
Oral Dermal Fish
to compound compound
Naproxen 3.29E-05 2.60E-06 1.16E-07 3.56E-05 4.00E-05 4.43E-06 1.16E-07 4.45E-05
Ibuprofen 6.09E-05 9.46E-06 4.82E-07 7.09E-05 7.41E-05 1.61E-05 4.82E-07 9.07E-05
Aspirin 5.94E-04 4.24E-06 1.57E-06 5.99E-04 7.22E-04 7.23E-06 1.57E-06 7.31E-04
Ketoprofen 1.95E-03 9.17E-05 1.72E-07 2.04E-03 2.37E-03 1.56E-04 1.72E-07 2.53E-03
Diclofenac 8.03E-03 1.82E-03 4.95E-05 9.89E-03 9.76E-03 3.11E-03 4.95E-05 1.29E-02
Overall total 1.27E-02 Overall total 1.63E-02
Teenagers Adults
Oral Dermal Fish Total risk due Oral Dermal Fish Total risk due to
to compound compound
Naproxen 4.86E-05 4.88E-06 3.61E-07 5.38E-05 6.98E-05 5.57E-06 2.83E-07 7.56E-05
Ibuprofen 9.00E-05 1.78E-05 1.50E-06 1.09E-04 1.29E-04 2.03E-05 1.18E-06 1.51E-04
Aspirin 8.77E-04 7.96E-06 4.89E-06 8.90E-04 1.26E-03 9.08E-06 3.83E-06 1.27E-03
Ketoprofen 2.88E-03 1.72E-04 5.35E-07 3.05E-03 1.24E-03 5.89E-05 1.26E-07 1.30E-03
Diclofenac 1.19E-02 3.42E-03 1.54E-04 1.54E-02 5.12E-03 1.17E-03 3.62E-05 6.32E-03
Overall total 1.95E-02 Overall total 9.13E-03

Table S2. Probabilistic hazard quotients (max and min) among different age groups: Pathway specific risks
Children 1 Children 2
Type of Risk
Mean Max. Min. Mean Max. Min.

Water Ingestion 1.07E-02 3.17E-02 1.11E-03 1.30E-02 3.28E-02 1.52E-03

Dermal contact 1.93E-03 7.56E-03 4.35E-05 3.29E-03 1.21E-02 2.43E-04

with water

Fish ingestion 5.18E-05 9.00E-04 2.63E-09 5.18E-05 8.99E-04 6.81E-09

Total Risk 1.27E-02 3.67E-02 1.79E-03 1.63E-02 4.14E-02 3.24E-03

Teenagers Adults
Type of Risk Mean Max. Min. Mean Max. Min.
Water Ingestion 1.58E-02 4.41E-02 1.56E-03 7.82E-03 2.26E-02 1.04E-03

Dermal contact 3.62E-03 1.71E-02 3.57E-04 1.26E-03 6.46E-03 6.72E-05

with water

Fish ingestion 1.62E-04 7.79E-04 1.93E-06 4.17E-05 3.32E-04 8.38E-08

 Total Risk 1.95E-02 5.92E-02 3.16E-03 9.13E-03 2.56E-02 1.57E-03

Table S3. Contaminant based intakes (mg/kg/d) for different age groups and exposure pathways
Contaminant Children 1 Children 2
Oral Dermal Fish Oral Dermal Fish
Naproxen 1.79E-06 1.41E-07 6.29E-09 1.19E-06 1.32E-07 3.44E-09

Ibuprofen 7.95E-06 1.23E-06 6.29E-08 5.29E-06 1.15E-06 3.45E-08

Aspirin 4.20E-05 2.99E-07 1.11E-07 2.79E-05 2.80E-07 6.07E-08

Ketoprofen 6.36E-06 2.99E-07 5.59E-10 4.23E-06 2.79E-07 3.06E-10

Diclofenac 6.55E-06 1.49E-06 4.03E-08 4.36E-06 1.39E-06 2.21E-08

Teenagers Adults
Oral Dermal Fish Oral Dermal Fish
Naproxen 8.16E-07 8.20E-08 6.06E-09 7.87E-07 6.27E-08 3.18E-09

Ibuprofen 3.63E-06 7.17E-07 6.06E-08 3.50E-06 5.48E-07 3.19E-08

Aspirin 1.92E-05 1.74E-07 1.07E-07 1.85E-05 1.33E-07 5.61E-08

Ketoprofen 2.90E-06 1.73E-07 5.39E-10 2.80E-06 1.33E-07 2.83E-10

Diclofenac 2.99E-06 8.62E-07 3.89E-08 2.88E-06 6.60E-07 2.04E-08

Calculations for Hazard quotient

Calculations of Hazard quotient (HQ) values for all the compounds and for all the pathways
are shown below. Table S4 provides estimations of CDI values for each pathway; Tables S5
and S6 show the calculations of ADI and hazard quotients, respectively.
Table S4: Estimation of CDI values for oral, dermal and fish ingestion pathways
Compound Cw C w x IR C w x CF 1 x SAevent x Kp x teventC w x BCF x FR x CF 2
(mg/L) CDI ingestion= CDI dermal= CDI fish=¿
BW BW BW
(mg/kg.d) (mg/kg.d) (mg/kg.d)

Naproxen 28.1 x −6 −6 −3 −6 −3
10-6
28.1 x 10 x 0.65 28.1 x 10 x 10 x 5838 x 0.0115 x 0.77
28.1 x 10 x 4 x 0.57 x 10
10.22 10.22 10.22
−6 −7 −9
¿ 1.79 x 10 ¿ 1.42 x 10 ¿ 6.28 x 10
Ibuprofen 125 x −6 −6 −3 −6 −3
10-6
125 x 10 x 0.65 125 x 10 x 10 x 5838 x 0.0226 x 0.77
125 x 10 x 9 x 0.57 x 10
10.22 10.22 10.22
−6 −6 −8
¿ 7.95 x 10 ¿ 1.24 x 10 ¿ 6.29 x 10
Aspirin 660 x Similarly Similarly Similarly
10-6
−5 −7 −7
¿ 4.19 x 10 ¿ 2.99 x 10 ¿ 1.11 x 10
Ketoprofen 100 x −6 −7 −10
10-6
¿ 6.36 x 10 ¿ 2.99 x 10 ¿ 5.59 x 10
Diclofenac 103 x −6 −6 −8
10-6
¿ 6.55 x 10 ¿ 1.49 x 10 ¿ 4.03 x 10

For 0 to 5 years (Values from Table 4): IR = 0.65 L/d; BW = 10.22 kg; SAevent = 5838 cm2; tevent= 0.77 h/d; FR = 0.57 g/d ; Kp
(cm/h) value for each compound taken from Table 6; CF1 (L/cm3) = 1 x 10-3
CF2 (kg/g) = 1 x 10-3
Table S5: Estimation of Acceptable daily intake (ADI) values for NSAIDs based on 0 to 5 year age
group
Compound UFcomposite = UF1 x UF2 x UF3x TD TD
ADI=
UF4 x UF5 (mg/d) BW x UF composite
(no units) (mg/kg.d)
Naproxen 1 x 3 x 10 x 10 x 3 = 900 500 = 500/(10.22 x 900) = 0.0544
Ibuprofen 1 x 3 x 10 x 10 x 3 = 900 1200 =1200/(10.22 x 900) = 0.130
Aspirin 1 x 3 x 10 x 10 x 3 = 900 650 =650/(10.22 x 900) = 0.0707
Ketoprofen 1 x 10 x 10 x 10 x 3 = 3000 100 =100/(10.22 x 3000) = 0.0033
Diclofenac 1 x 10 x 10 x 10 x 3 = 3000 25 =25/(10.22 x 3000) = 0.0008
UF1, UF3, UF4, UF5 values taken from Table 5a; UF2 values taken from Table 5b;
Mean BW(10.22 kg) for 0 to 5 years taken from Table 4; TD values taken from Table 6

Table S6: Hazard quotient calculation for oral, dermal and fish ingestion pathways: 0 to 5
years
Compound Oral risk Dermal risk Fish ingestion risk
CDI ingestion CDIdermal CDIfish
HQo= HQd= HQf =
ADI ADI ADI
Naproxen
−6 −7 −9
1.79 x 10 1.42 x 10 6.28 x 10
0.0544 0.0544 0.0544

= 3.29 x 10−5 = 2.61 x 10−6 = 1.15 x 10−7

Ibuprofen
−6 −6 −8
7.95 x 10 1.24 x 10 6.29 x 10
0.130 0.130 0.130

= 6.09 x 10−5 = 9.54 x 10−6 = 4.83 x 10−7

Aspirin Similarly Similarly Similarly
−4 −6 −6
5.94 x 10 4.24 x 10 1.57 x 10
Ketoprofen −3 −5 −7
1.95 x 10 9.17 x 10 1.72 x 10
Diclofenac −3 −3 −5
8.03 x 10 1.82 x 10 4.95 x 10
−2 −3 −5
Sum of HQs 1.07 x 10 1.93 x 10 5.18 x 10
CDIingestion, CDIdermal and CDIfish values were used from Table S4; ADI values were used from Table S5

The final risk values such as 1.07E-02 (oral risk), 1.93E-03 (dermal risk) and 5.18E-05 (fish
ingestion risk) are shown in Table S6.