1. Supplementary material

Study Meats Compounds Cooking Methods N of sampl

e types

Detection Method

Limit of Detection

Percent of non-detects per compound

Keating et al, 2000 ground beef and beef steak

PhIP, MeIQx, 4,8-DiMeIQx pan-fried 5 fluorescence

0.02 ppb, 0.015 ppb, 0.005 ppb

30%, 57%, 27%

Balogh et al, 2000 ground beef PhIP, IQ, MeIQ, MeIQx, 4,8-DiMeIQx,

pan fried 11 fluorescence

Not reported

0

Sinha et al, 1995 chicken, breast and whole

PhIP, MeIqx, 4,8-DiMeIQx pan-fried, broiled, grilled, baked, boiled

13 fluorescence

0.2 ppb 14%, 57%, 0

Sinha et al, 1998 ground beef, beef steak, and beef drippings

PhIP, MeIQx, 4,8-DiMeIQx, IQ, MeIQ

pan-fried, broiled, grilled

30 fluorescence

0.2 ppb 47%, 40%, 93%, 100%, 100%

Sinha et al, 1998 bacon, pork sausage, ground pork, ham slices, and pork chops, beef/pork hot dogs, and bacon drippings

PhIP, MeIQx, 4,8-DiMeIQx, IQ, MeIQ

pan-fried, broiled, microwaved, broiled, boiled

34 fluorescence

0.2 ppb 74%, 53%, 100%, 100%, 100%

Oz et al, 2010 chicken breast and trout fillet

PhIP, MeIQx, 4,8-DiMeIQx, IQ, MeIQ, AαC, MeAαC

microwaved, baked, pan-fried, barbecued

40 fluorescence

0.003 ppb 100%, 80%, 43%, 28%, 53%, 100%, 100%

Oz et al, 2010 beef steak and lamb chops

PhIP, MeIQx, 4,8-DiMeIQx, IQ, MeIQ

microwaved, baked, pan-fried, barbecued

40 fluorescence

0.003 ppb 92%, 87%, 82%, 80%, 92%

Skog et al, 1997 cod fillet, herring fillet, lamb chop, chicken breast, reindeeer fillet, cubed pork steak, beef/pork falun, pan drippings, and beef gravy

PhIP, MeIQx, 4,8-DiMeIQx, IQ, MeIQ, Trp-P-1, Trp-P2

pan-fried, smoked, baked

70 fluorescence

0.01 ppb 14%, 27%, 51%, 98%, 97%

1

Knize et al, 1994 ground beef PhIP, MeIQx, 4,8-DiMeIQx, IQ

pan-fried 12 fluorescence

0.1 ppb 25%, 17%, 25%, 33%

Knize et al, 1998 ground beef, beef steak, pork ribs, chicken breast and thigh

PhIP, MeIQx, 4,8-DiMeIQx, IQ

pan-fried, grilled, smoked, baked, rotisserie

22 fluorescence

0.1 ppb 5%, 77%, 86%, 100%

Puangsombat et al, 2012

beef steak, pork steak, ground pork, bacon, chicken breast, chicken thigh, catfish, salmon, tilapia

PhIP, MeIQx, 4,8-DiMeIQx, IQ

oven, smoker, rotisserie

22 fluorescence

0.004 ppb 0%, 23%, 85%, 23%

Liao et al, 2010 chicken breast and duck breast

PhIP, MeIQx, 4,8-DiMeIQx, IQ, MeIQ, AαC, MeAαC, TrP-P-1, TrP-P-2, Glu-P2

fried, deep fried, grilled,

8 fluorescence

0.1 ppb 13%, 25%, 25%, 64%, 25%, 0%, 0%, 83%, 38%, 100%

Pais et al, 1999 beef steak, chicken breast, chicken thigh, turkey breast, pork steak, and whole cod

PhIP, MeIQx, 4,8-DiMeIQx, IQ, MeIQ, AαC, MeAαC, TrP-P-1, TrP-P-2, Glu-P2

Grilled 12 fluorescence

0.1 ppb 0%, 8%, 8%, 83%, 83%, 100%, 100%, 83%, 100%, 100%

Puangsombat et al, 2011

beef hotdog, beef/turkey hotdog, deli beef, deli ham, deli turkey, pepperoni, bacon, whole chicken

PhIP, MeIQx, 4,8-DiMeIQx, IQ

baked, smoked, rotisserie

13 fluorescence

0.004 ppb 100%, 23%, 85%, 23%

Iwasaki et al, 2010 beef steak, ground beef, pork steak, pork sausage, chicken breast, sardine, and salmon (whole and fillet)

PhIP, MeIqx, 4,8-DiMeIQx fried, grilled, churrasco

99 MS 0.005 38%, 45%, 54%

Khan et al, 2013 salmon fillet, tuna fillet, sardine fillet, swordfish fillet, hake, angler fish, sole, squid, and cuttlefish

PhIP, MeIQx, 4,8-DiMeIQx, IQ, MeIQ, AαC, MeAαC, TrP-P-1, TrP-P-2

Fried 10 MS 0.01-0.02 0%, 40%, 50%, 70%, 90%, 90%, 80%, 100%, 100%

Ni et al, 2008 pork steak, pork sausage, bacon, chicken breast, ground beef, beef steak

PhIP, MeIQx, 4,8-DiMeIQx, IQ

fried, broiled, grilled, baked

26 MS 0.03 12%, 12%, 12%, 19%

2

Viegas et al, 2012 beef steak, salmon fillet, chicken breast

PhIP, MeIQx, 4,8-DiMeIQx, IQ, AαC, MeAαC, TrP-P-1, TrP-P-2

grilled, churrasco (barbecued), baked

6 fluorescence

0.06 0%, 17%, 67%, 100%, 0%, 0%, 100%, 100%

Supplemental Table 1: Some characteristics of the 18 studies selected for inclusion in the meta-analysis for predictive models of HCA compounds in meats with different cooking methods.

Study Meats Compounds Cooking Methods

N of sample types

Detection Method

Limit of Detection

Percent of non-detects per compound

Kazerouni et. al.,

2005

chicken breast, whole chicken, poultry gravy, chicken soup, crab, perch, fish fillet, tuna, bread, ground beef, beef steak, beef roast, beef gravy, bacon, bacon fat, salami, bologna, ham slice, smoked ham, deli ham, pork chop, hot dog, pork sausage, pork ribs, pork sausage, pepperoni pizza

BaP broiled, pan-fried, grilled, stewed, roasted, baked, smoked, microwaved

165 fluorescence 0.005 10%

Lawrence et. al.,

1984

ground beef, haddock, cod, digby chix, herring, char, nova sal, sardine, saithe, kippers, cod liver, beef spread, pork spread, mussel, oyster, lobster

BaP, BaA, BbF, DahA, Chy, IP

smoked, raw, boiled, fried, deep fried, grilled, baked, broiled

40 fluorescence 0.01 43%, 13%, 30%, 50%, 50%, 20%

Chen et. al. 1997

duck breast BaP, BaA, Chy, BbF, BkF, DahA, BghiP, IP

barbecued, liquid-smoked, roasted, steamed, smoked

18 MS 1.1 18%, 10%, 10%, 100%, 33%, 100%, 100%, 39%

Hitzel et. al. 2013

hot dog, mini sausage BaP, BaA, Chy, BbF, BkF, DahA, BghiP, IP

cured, smoked 20 MS 0%

Farhadian et. al. 2010

ikan bakar, beef satay, chicken satay, beef kebab, chicken kebab, chicken, tandoori chicken, whole chicken

BaP, BbF barbecued 9 MS 0.03 0%

Wretling et. al. 2010

ham, bacon, pork tenderloin, pork shoulder, chicken, turkey, sausage, elk sausage, herring, salmon, trout, mackerel, whitefish

BaP, BaA, Chy, BbF, BkF, DahA, BghiP, IP

smoked, indirect-smoked, sauna-smoked,

71 MS 0.3 50%, 35%, 32%, 49%, 52%, 94%, 56%, 55%

Ciercierska et. al. 2013

bread BaP, BaA, Chy, BbF, BkF, DahA, BghiP, IP

toasted, baked 3 MS 0.12 100%, 0%, 100%,33%, 67%, 100%, 100%, 100%

Rey-Salgueir

o et al. 2008

bread BaP, BaA, Chy, BbF, BkF, DahA, BghiP, IP

toasted, baked 4 fluorescence 0.02 50%, 50%, 100%, 75%, 50%, 100%, 100%, 100%

White et donar kebab, chicken kebab, chicken shish kebab, shish BaP, BaA, Chy, roasted, 339 MS 0.01-0.25 47%, 34%, 26%,

3

al. 2007 kebab, kofte kebab, whole chicken, chicken parts, chinese chicken, bacon joint, ham shank, stuffed belly pork joint, bbq ribs, sausage, ground beef burger, chicken burger, veggie burger, hot dog, hot pork sandwich, hot beef sandwich, hot chicken sandwich, hot lamb sandwich, panini, pizza, naan, haddock, fried chicken, fried rice, sausage, beef burger, lamb chops, beef steak, salmon, beef roast, bread

BbF, BkF, DahA, BghiP, IP

barbecued, toasted (bread), pan-fried, deep fried, grilled, grilled bread, cured, raw, stewed, boiled, microwaved

36%, 46%, 87%, 33%, 67%

Supplemental Table 2: Some characteristics of the 9 studies selected for inclusion in the meta-analysis for predictive models of PAH compounds in meats with different cooking methods.

Summary of HCA data available (N samples (n studies), mean concentration (sd, %<LOD), mean Temp, mean Time) Beef Fish Poultry PorkPhIP:

Baked 27 (4), 0.71 (1.05, 0.19), 134, 80 16 (2), 3.46 (2.22, 0.25), 177, 12 18 (5), 0.11 (0.15, 0.44), 158, 20 20 (2), 1.55 (0.89, 0), 177, 70Barbecued 86 (5), 6.85 (7.3, 0.14), 240, 19 16 (3), 5.05 (8.51, 0.38), 261, 37 69 (7), 33.04 (83.74, 0.23), 249, 29 2 (1), 3.16 (4.41, 0), 265, 34

Boiled - - 1 (1), 0.09 (NA, 1), 100, 90 -Broiled 31 (3), 1.73 (2.29, 0.42), 189, 25 - 13 (2), 51.32 (47.27, 0), 90, 16 6 (2), 16.51 (9.21, 0), 177, 6

Deep Fried - - 6 (1), 1.84 (0.59, 0), 180, 10 -Fried 268 (11), 4.54 (7.53, 0.11), 196, 17 87 (6), 9.08 (22.36, 0.17), 209, 10 89 (8), 10.06 (14.11, 0.16), 214, 21 67 (6), 2.89 (5, 0.36), 192, 19

Microwaved 4 (1), 0.01 (0, 1), 100, 4 4 (1), 0 (0, 1), 100, 3 4 (1), 0 (0, 1), 100, 8 3 (1), 1.04 (1.79, 0.67), 100, 3Rotisserie - - 16 (2), 2.04 (3.77, 0), 26, 60 -

Smoked - - - 32 (2), 2.25 (3.42, 0), 141, 120MeIQx:

Baked 27 (4), 1.25 (2.59, 0.15), 134, 80 16 (2), 1.6 (1.2, 0.25), 177, 12 12 (4), 0.06 (0.05, 0.58), 137, 20 20 (2), 0.1 (0.12, 0.8), 177, 70Barbecued 75 (5), 1.3 (1.94, 0.04), 238, 19 12 (3), 1.35 (1.63, 0.17), 259, 25 58 (7), 1.47 (1.92, 0.05), 248, 31 2 (1), 0.69 (0.66, 0), 265, 34

Boiled - - 1 (1), 0.02 (NA, 1), 100, 90 -Broiled 25 (3), 0.31 (0.5, 0.32), 190, 29 - 13 (2), 1.11 (1.23, 0.23), 90, 16 6 (2), 2.27 (1.29, 0.17), 177, 6

Deep Fried - - 6 (1), 0.79 (0.23, 0), 180, 10 -Fried 254 (11), 1.94 (2.02, 0.04), 198, 18 78 (6), 0.63 (0.97, 0.35), 210, 10 84 (8), 0.94 (1.14, 0.07), 215, 22 62 (6), 2.03 (1.99, 0.15), 193, 18

Microwaved 4 (1), 0.02 (0.01, 1), 100, 4 4 (1), 0 (0, 1), 100, 3 4 (1), 0.01 (0, 1), 100, 8 3 (1), 0.64 (0.77, 0.33), 100, 3Rotisserie - - 16 (2), 1.1 (1.68, 0), 26, 60 -

Smoked - - - 32 (2), 0.11 (0.12, 0.5), 141, 120Supplemental Table 3: Summary of the HCA data available for the meta-regression analysis. The following information is included for each PAH compound, and combination of meat type and cooking method: number of samples (and number of studies they were extracted from), mean concentration (and standard deviation, as well as proportion of values below the Limit of Detection), mean cooking temperature in Celsius, and mean cooking time in minutes.

4

Summary of PAH data available (N samples (n studies), mean concentration (sd, %<LOD), mean Temp, mean Time)Beef Fish Poultry Pork Bread

BaP:Baked 3 (1), 0.01 (0, 1), 160, 107 - - 3 (1), 0.86 (0.82, 0.33), 150, 180 19 (3), 0.06 (0.06, 0.68), 221, 33

Grilled - - - - 9 (1), 0.05 (0.02, 0), 180, 4

Toasted - - - - 23 (2), 0.29 (0.36, 0.43), 318, 5

Barbecued 104 (3), 5.05 (6.29, 0.01), 227, 16 44 (3), 0.79 (0.85, 0), 177, 17 164 (4), 1.85 (2.27, 0.14), 209, 32 38 (2), 4.07 (7.16, 0.11), 180, 20 -

Boiled 5 (1), 0.02 (0, 0.4), 100, 26 5 (2), 0.23 (0.31, 0.6), 100, 15 11 (2), 0.01 (0.02, 0.91), 100, 63 - -

Broiled 10 (2), 1.13 (1.57, 0.6), 181, 13 3 (1), 0.18 (0.07, 0), 80, 14 3 (1), 0.23 (0.22, 0), 114, 31 7 (1), 0 (0, 1), 177, 8 -

Dried - - - - -

Fried 53 (3), 0.03 (0.04, 0.7), 182, 23 17 (2), 0.03 (0.03, 0.94), 202, 18 23 (2), 0.02 (0.03, 0.83), 201, 66 35 (2), 0.02 (0.03, 0.71), 187, 24 -

Microwaved - - - 2 (1), 0.01 (0.01, 0.5), 100, 3 -

Raw 3 (1), 0.02 (0, 0.67), 0, 0 2 (2), 0.43 (0.53, 0.5), 0, 0 2 (1), 0.03 (0.01, 1), 0, 0 3 (1), 0.04 (0.03, 0.67), 0, 0 -

Roasted 14 (2), 0.02 (0.01, 1), 160, 73 - 20 (3), 0.06 (0.07, 0.85), 190, 59 7 (1), 0 (0, 1), 180, 63 -

Indirect smoked - 6 (1), 0.02 (0.01, 1), 180, 63 3 (1), 0.39 (0.16, 1), 50, 1440 6 (1), 0.08 (0.16, 0.83), 180, 63 -

Sauna smoked - 1 (1), 8.4 (NA, 0), 180, 63 - 8 (1), 16.81 (9.33, 0), 180, 63 -

Smoked 1 (1), 0.1 (NA, 0), 121, 180 54 (3), 2.44 (3.99, 0.35), 76, 162 19 (2), 7.48 (4.61, 0.21), 73, 96 48 (5), 0.41 (0.42, 0.23), 39, 65 -

ChY:Baked - - - - 14 (2), 0.11 (0.06, 0.86), 233, 34

Grilled - - - - 9 (1), 0.18 (0.06, 0), 180, 4

Toasted - - - - 23 (2), 0.1 (0.08, 0.87), 318, 5

Barbecued 53 (1), 7.7 (8.2, 0), 227, 16 53 (1), 7.7 (8.2, 0), 227, 16 47 (2), 10.18 (13.2, 0.02), 209, 49 35 (1), 4.21 (5.22, 0.03), 180, 20 -

Boiled - - 9 (1), 0.03 (0.03, 1), 100, 60 - -

Broiled 2 (1), 1.95 (0.07, 0), 181, 13 2 (1), 1.95 (0.07, 0), 181, 13 - - -

Dried - - - - -

Fried 36 (2), 0.04 (0.03, 0.56), 182, 24 36 (2), 0.04 (0.03, 0.56), 182, 24 20 (1), 0.01 (0.02, 0.75), 201, 69 21 (1), 0.03 (0.04, 0.43), 187, 31 -

Microwaved - - - - -

Raw 3 (1), 0.06 (0.01, 0.67), 0, 0 3 (1), 0.06 (0.01, 0.67), 0, 0 2 (1), 0.02 (0, 1), 0, 0 3 (1), 0.06 (0.07, 0.67), 0, 0 -

Roasted 12 (1), 0.03 (0.02, 1), 160, 60 12 (1), 0.03 (0.02, 1), 160, 60 16 (2), 0.57 (0.51, 0.19), 194, 53 7 (1), 0.02 (0.02, 0.29), 180, 63 -

Indirect smoked - - 3 (1), 0.14 (0.11, 1), 50, 1440 6 (1), 0.47 (0.63, 0.5), 180, 63 -

Sauna smoked - - - 8 (1), 30.09 (18.31, 0), 180, 63 -

Smoked - - 19 (2), 5.69 (5.45, 0.21), 73, 96 44 (3), 1.22 (1.02, 0.11), 31, 49 -

5

BaA:Baked - - - - 14 (2), 0.06 (0.01, 0), 233, 34

Grilled - - - - 9 (1), 0.06 (0.02, 0), 180, 4

Toasted - - - - 23 (2), 0.73 (0.89, 0.43), 318, 5

Barbecued 53 (1), 5.23 (6, 0), 227, 16 24 (1), 1.33 (1.39, 0), 177, 18 47 (2), 3.32 (5.66, 0.02), 209, 49 - -

Boiled - 3 (1), 1.43 (0.74, 0), 100, 12 9 (1), 0.04 (0.05, 1), 100, 60 - -

Broiled 4 (1), 1.83 (0.78, 0), 181, 13 - - - -

Dried - - - - -

Fried 38 (2), 0.02 (0.04, 0.55), 182, 24 16 (1), 0.04 (0.02, 0.94), 202, 17 20 (1), 0.01 (0.01, 0.9), 201, 69 - -

Microwaved - - - - -

Raw 3 (1), 0.03 (0.01, 0.67), 0, 0 2 (2), 14.54 (20.45, 0.5), 0, 0 2 (1), 0.03 (0, 1), 0, 0 - -

Roasted 12 (1), 0.02 (0.01, 1), 160, 60 - 16 (2), 2.69 (2.44, 0.31), 194, 53 - -

Indirect smoked - 6 (1), 0.1 (0.15, 0.83), 180, 63 3 (1), 0.21 (0.13, 1), 50, 1440 - -

Sauna smoked - 1 (1), 12.9 (NA, 0), 180, 63 - - -

Smoked 1 (1), 0.8 (NA, 0), 121, 180 53 (2), 6.63 (13.14, 0.13), 75, 163 19 (2), 8.9 (6.37, 0.21), 73, 96 - -

BkF:Baked - - - - 14 (2), 0.05 (0.05, 0.57), 233, 34

Grilled - - - - 9 (1), 0.03 (0.01, 0), 180, 4

Toasted - - - - 23 (2), 0.1 (0.13, 0.43), 318, 5

Barbecued 91 (2), 1.19 (2.11, 0.03), 227, 15 43 (2), 0.17 (0.36, 0.09), 177, 16 161 (3), 0.63 (1.77, 0.01), 209, 31 35 (1), 1.31 (2.12, 0.11), 180, 20 -

Boiled - - 9 (1), 0 (0, 1), 100, 60 - -

Broiled - - - - -

Dried - - - - -

Fried 34 (1), 0.01 (0.01, 0.88), 182, 25 16 (1), 0.01 (0.01, 0.94), 202, 17 20 (1), 0 (0.01, 0.95), 201, 69 21 (1), 0.01 (0.01, 0.9), 187, 31 -

Microwaved - - - - -

Raw 3 (1), 0.02 (0.01, 0.67), 0, 0 1 (1), 0.02 (NA, 1), 0, 0 2 (1), 0 (0, 1), 0, 0 3 (1), 0.02 (0.01, 0.67), 0, 0 -

Roasted 12 (1), 0.01 (0, 1), 160, 60 - 16 (2), 0.03 (0.09, 0.94), 194, 53 7 (1), 0 (0, 1), 180, 63 -

Indirect smoked - 6 (1), 0.01 (0.01, 1), 180, 63 3 (1), 0.1 (0, 0), 50, 1440 6 (1), 0.09 (0.16, 0.83), 180, 63 -

Sauna smoked - 1 (1), 4.2 (NA, 0), 180, 63 - 8 (1), 9.74 (4.71, 0), 180, 63 -

Smoked - 32 (1), 1.48 (2.6, 0.34), 76, 174 19 (2), 2.86 (2.54, 0.21), 73, 96 44 (3), 0.19 (0.16, 0.16), 31, 49 -

BbFBaked - - - - 14 (2), 0.09 (0.05, 0.29), 233, 34

Grilled - - - - 9 (1), 0.05 (0.02, 0), 180, 4

Toasted - - - - 23 (2), 0.28 (0.46, 0.65), 318, 5

Barbecued 91 (2), 4.45 (4.62, 0), 227, 15 43 (2), 1.05 (0.83, 0), 177, 16 161 (3), 1.68 (2.7, 0.25), 209, 31 35 (1), 2.76 (4, 0.09), 180, 20 -

Boiled - 3 (1), 0.36 (0.32, 0.33), 100, 12 9 (1), 0.02 (0.03, 1), 100, 60 - -

6

Broiled 4 (1), 1.78 (0.99, 0), 181, 13 - - - -

Dried - - - - -

Fried 38 (2), 0.02 (0.02, 0.58), 182, 24 16 (1), 0.03 (0.02, 0.94), 202, 17 20 (1), 0.01 (0.01, 0.95), 201, 69 21 (1), 0.01 (0.02, 0.67), 187, 31 -

Microwaved - - - - -

Raw 3 (1), 0.02 (0.01, 0.67), 0, 0 2 (2), 1.29 (1.71, 0.5), 0, 0 2 (1), 0.02 (0.01, 1), 0, 0 3 (1), 0.03 (0.02, 0.33), 0, 0 -

Roasted 12 (1), 0.02 (0.01, 1), 160, 60 - 16 (2), 5.71 (5.19, 0.25), 194, 53 7 (1), 0.01 (0.01, 0.86), 180, 63 -

Indirect smoked - 6 (1), 0.03 (0.02, 1), 180, 63 3 (1), 0.14 (0.11, 1), 50, 1440 6 (1), 0.07 (0.12, 0.83), 180, 63 -

Sauna smoked - 1 (1), 5.5 (NA, 0), 180, 63 - 8 (1), 11.18 (6.02, 0), 180, 63 -

Smoked 1 (1), 0.2 (NA, 0), 121, 180 53 (2), 3.39 (7.32, 0.25), 75, 163 19 (2), 6.46 (6.06, 0.21), 73, 96 45 (4), 0.37 (0.31, 0.18), 33, 52 -

DahA:Baked - - - - 14 (2), 0.06 (0.08, 1), 233, 34

Grilled - - - - 9 (1), 0.13 (0.03, 1), 180, 4

Toasted - - - - 23 (2), 0.07 (0.09, 1), 318, 5

Barbecued 53 (1), 0.43 (0.59, 0.53), 227, 16 24 (1), 0.07 (0.11, 0.92), 177, 18 47 (2), 0.09 (0.18, 0.96), 209, 49 35 (1), 0.38 (0.67, 0.6), 180, 20 -

Boiled - 3 (1), 0.04 (0.01, 1), 100, 12 9 (1), 0 (0, 1), 100, 60 - -

Broiled 4 (1), 0.85 (1.03, 0.5), 181, 13 - - - -

Dried - - - - -

Fried 38 (2), 0 (0, 1), 182, 24 16 (1), 0.06 (0.02, 1), 202, 17 20 (1), 0.01 (0, 1), 201, 69 21 (1), 0.02 (0.01, 1), 187, 31 -

Microwaved - - - - -

Raw 3 (1), 0 (0, 1), 0, 0 2 (2), 3.99 (5.54, 0.5), 0, 0 2 (1), 0.01 (0, 1), 0, 0 3 (1), 0.03 (0.02, 1), 0, 0 -

Roasted 12 (1), 0 (0, 1), 160, 60 - 16 (2), 0.01 (0.02, 1), 194, 53 7 (1), 0.01 (0.01, 1), 180, 63 -

Indirect smoked - 6 (1), 0.02 (0.01, 1), 180, 63 3 (1), 0.04 (0.05, 1), 50, 1440 6 (1), 0 (0, 1), 180, 63 -

Sauna smoked - 1 (1), 0.01 (NA, 1), 180, 63 - 8 (1), 0.2 (0.28, 0.63), 180, 63 -

Smoked - 45 (2), 0.48 (1.61, 0.89), 75, 160 19 (2), 0 (0, 1), 73, 96 13 (2), 0 (0, 1), 52, 95 -

IP:Baked - - - - 14 (2), 0.07 (0.05, 1), 233, 34

Grilled - - - - 9 (1), 0.09 (0.03, 0.89), 180, 4

Toasted - - - - 23 (2), 0.07 (0.06, 1), 318, 5

Barbecued 53 (1), 4.54 (5.39, 0.32), 227, 16 24 (1), 0.5 (0.84, 0.42), 177, 18 47 (2), 1.68 (1.98, 0.21), 209, 49 35 (1), 3.55 (5.96, 0.31), 180, 20 -

Boiled - 3 (1), 1.47 (1.17, 0.33), 100, 12 9 (1), 0.03 (0.01, 1), 100, 60 - -

Broiled 4 (1), 2.85 (2.46, 0.25), 181, 13 - - - -

Dried - - - - -

Fried 38 (2), 0 (0, 1), 182, 24 16 (1), 0.09 (0.04, 1), 202, 17 20 (1), 0.02 (0.01, 0.95), 201, 69 21 (1), 0.05 (0.02, 1), 187, 31 -

Microwaved - - - - -

Raw 3 (1), 0.02 (0.01, 1), 0, 0 2 (2), 3.06 (4.16, 0.5), 0, 0 2 (1), 0.04 (0.04, 1), 0, 0 3 (1), 0.07 (0.03, 1), 0, 0 -

Roasted 12 (1), 0 (0, 1), 160, 60 - 16 (2), 0.07 (0.04, 1), 194, 53 7 (1), 0.03 (0.01, 1), 180, 63 -

7

Indirect smoked - 6 (1), 0.06 (0.02, 1), 180, 63 3 (1), 0.19 (0, 1), 50, 1440 6 (1), 0.06 (0.12, 0.83), 180, 63 -

Sauna smoked - 1 (1), 5.4 (NA, 0), 180, 63 - 8 (1), 10.23 (5.17, 0), 180, 63 -

Smoked - 40 (2), 2.91 (5.97, 0.38), 76, 158 19 (2), 3.79 (2.02, 0.21), 73, 96 44 (3), 0.23 (0.21, 0.23), 31, 49 -

BghiPBaked - - - - 14 (2), 0.09 (0.18, 0.86), 233, 34

Grilled - - - - 9 (1), 0.3 (0.3, 0.11), 180, 4

Toasted - - - - 23 (2), 0.05 (0.04, 0.87), 318, 5

Barbecued 53 (1), 5.86 (6.78, 0), 227, 16 24 (1), 0.63 (0.8, 0), 177, 18 47 (2), 0.4 (0.54, 0.43), 209, 49 35 (1), 4.28 (7.23, 0.03), 180, 20 -

Boiled - - 9 (1), 0.03 (0.03, 1), 100, 60 - -

Broiled - - - - -

Dried - - - - -

Fried 34 (1), 0.02 (0.02, 0.5), 182, 25 16 (1), 0.01 (0.01, 0.75), 202, 17 20 (1), 0.01 (0.01, 0.9), 201, 69 21 (1), 0.01 (0.01, 0.52), 187, 31 -

Microwaved - - - - -

Raw 3 (1), 0.01 (0.01, 0.67), 0, 0 1 (1), 0.02 (NA, 1), 0, 0 2 (1), 0.1 (0.12, 0.5), 0, 0 3 (1), 0.02 (0.01, 0.67), 0, 0 -

Roasted 12 (1), 0.01 (0.01, 1), 160, 60 - 16 (2), 0.04 (0.04, 0.94), 194, 53 7 (1), 0.01 (0.02, 0.71), 180, 63 -

Indirect smoked - 6 (1), 0.01 (0.01, 1), 180, 63 3 (1), 0.08 (0.07, 1), 50, 1440 6 (1), 0.05 (0.06, 1), 180, 63 -

Sauna smoked - 1 (1), 4.2 (NA, 0), 180, 63 - 8 (1), 7.95 (5.07, 0), 180, 63 -

Smoked - 32 (1), 1.73 (4.82, 0.41), 76, 174 19 (2), 0.01 (0.02, 1), 73, 96 44 (3), 0.23 (0.17, 0.16), 31, 49 -

Supplemental Table 4: Summary of the PAH data available for the meta-regression analysis. The following information is included for each PAH compound, and combination of meat type and cooking method: number of samples (and number of studies they were extracted from), mean concentration (and standard deviation, as well as proportion of values below the Limit of Detection), mean cooking temperature in Celsius, and mean cooking time in minutes.

8

Main Effects Significant Interactions

Chem Meat Model Mea

t Typ

e

Cook

ing

Met

hod

Food

For

mPa

n Te

mpe

ratu

reCo

okin

g Ti

me

Type

of F

uel

Perc

ent o

f Fat

in R

aw M

eat

Ope

n Fl

ame

Expo

sure

Shel

lfish

(Y/N

)O

il in

Pan

Flip

ped

at le

ast o

nce

Skin

-on

(Y/N

)Ba

rbec

ued

(Y/N

)

Fish

gro

up

Met

hod

X Fo

rm

Met

hod

X Ti

me

Met

hod

X Fi

sh G

roup

Food

For

m X

Coo

king

Tim

e

Tim

e *e

xp(-1

/Tem

p)Co

okin

g Ti

me

X %

Fat

Met

hod

X Fo

rm X

Pan

Tem

p

Pan

Tem

p X

% F

at

Met

hod

X Fo

rm X

Coo

king

Tim

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etho

d X

Tim

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xp(-1

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p)

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X Fo

rm X

% F

atO

pen

Flam

e X

Tim

e

Ope

n Fl

ame

X Pa

n Te

mp

Ope

n Fl

ame

X %

Fat

Ope

n Fl

ame

X Ti

me

*exp

(-1/T

emp)

Fuel

Use

d X

Barb

ecue

d (Y

/N)

Fuel

Use

d X

Cook

ing

Tim

eFu

el U

sed

X %

Fat

Fi

sh G

roup

X C

ooki

ng T

ime

BaP All NA ↑ ↓ X X XChY All NA X X ↑ ↑ ↓ ↓BaA All NA X ↓ ↓BkF All NA ↑ ↑ X X ↓BbF All NA ↑ ↑ ↓ X ↓DahA All NA X ↑ ↓ X ↑ X ↑IP All NA X ↑ ↓ X X ↑BghiP All NA X ↑ ↑ X ↑ X ↓ XPhIP All NA X ↓ ↓ X X X XMeIQx All NA X ↑ ↓ X X XBaP Beef 1 ↑ ↓ X ↓BaP Beef 2 X X X ↑ X XBaP Poultry 1 ↓ ↑ X ↓ XBaP Poultry 2 X ↓ XBaP Pork 1 X X ↓ ↑ X

9

BaP Pork 2 X X XBaP Seafood 1 X ↑ ↑ ↑ X ↓BaP Seafood 2 X ↓ ↑ ↑ XBaP Bread NA X ↑ ↑ ↓ChY Beef 1 ↑ ↑ ↓ChY Beef 2 X ↑ ↑ XChY Poultry 1 ↑ X ↑ChY Poultry 2 ↓ X ↓ChY Pork 1 X XChY Pork 2 X ↓ XChY Seafood 1 X ↓ XChY Seafood 2 X X XChY Bread NA X ↑ ↓ ↓BaA Beef 1 X ↓BaA Beef 2 ↑ X X ↓ XBaA Poultry 1 ↓ X ↓BaA Poultry 2 ↓ X ↓BaA Pork 1 X XBaA Pork 2 X XBaA Seafood 1 ↑ X XBaA Seafood 2 ↓ X XBaA Bread NA X ↑ ↑BkF Beef 1 X XBkF Beef 2 ↑ XBkF Poultry 1 X ↑BkF Poultry 2 X ↓BkF Pork 1 ↓ XBkF Pork 2 X XBkF Seafood 1 X X XBkF Seafood 2 ↓ ↑ X XBkF Bread NA X ↑ ↑BbF Beef 1 X ↓BbF Beef 2 ↓ ↑ X

10

BbF Poultry 1 ↑ X ↓BbF Poultry 2 X ↑ ↓ ↓BbF Pork 1 X X ↓BbF Pork 2 ↓ X XBbF Seafood 1 ↓ X ↑ X XBbF Seafood 2 X X XBbF Bread NA X ↓ ↓DahA Beef 1 X ↓ ↑DahA Beef 2 ↓ X XDahA Poultry 1 X XDahA Poultry 2 X ↑ XDahA Pork 1 X ↓ XDahA Pork 2 ↓ ↑ ↓DahA Seafood 1 X ↓ XDahA Seafood 2 ↑ X XDahA Bread NA X ↑ ↑IP Beef 1 ↑ ↓ XIP Beef 2 X X ↑IP Poultry 1 ↑ X XIP Poultry 2 X ↑ ↑ ↓IP Pork 1 X ↓IP Pork 2 X ↓IP Seafood 1 ↓ X X XIP Seafood 2 ↑ X XIP Bread NA X ↑ ↓ ↑BghiP Beef 1 ↑ ↑ X ↓ ↑ X ↓ XBghiP Beef 2 ↑ ↑ X ↓ ↑ X ↓ XBghiP Poultry 1 ↑ ↑ X ↓BghiP Poultry 2 ↑ X ↑ ↓BghiP Pork 1 ↓ X XBghiP Pork 2 X XBghiP Seafood 1 X X XBghiP Seafood 2 ↓ X X X

11

BghiP Bread NA X ↑ ↓PhIP Beef 1 ↑ ↑ ↑ X ↑ XPhIP Beef 2 ↑ ↑ ↑ X ↑PhIP Poultry 1 ↑ ↓ XPhIP Poultry 2 ↑ ↓ XPhIP Pork 1 X X ↑ ↑ ↓PhIP Pork 2 X ↑ ↑PhIP Seafood 1 X ↑ X XPhIP Seafood 2 XMeIQx Beef 1 ↑ ↑ ↑ X X XMeIQx Beef 2 ↑ ↓MeIQx Poultry 1 ↑ ↑ ↓ X ↑MeIQx Poultry 2 ↑ ↓ X ↑MeIQx Pork 1 ↑ ↑ ↓ XMeIQx Pork 2 X ↑MeIQx Seafood 1 ↑ ↑ X X XMeIQx Seafood 2 ↑ X X

Total Frequency 6 27 12 29 66 38 24 6 4 3 3 6 2 12 49 2 2 1 26 4 1 1 2 1 1 4 1 3 1 1 11 3 1Supplemental Table 5: Summary of fixed effects and significant fixed effect interactions included in the models for each meat and cooking category for all compounds, in addition to the random effect of study. Only variables and interactions which improved the AIC and fit of the model are included here. For food categories where all values for time and temperature predictors were imputed, simpler models (Model 2) were estimated omitting temperature and/or time. Since time data was more complete across cooking categories, this variable was often applied in Model 2 where temperature was omitted, as time was partially imputed but temperature was completely imputed. For beef, model 2 is applied to the barbecued and broiled foods. Model 2 for poultry was used for barbecued and smoked foods, for pork it was used for boiled and barbecued foods, and for seafood, barbecued, boiled, smoked, and broiled foods. Where the variable is continuous or binary and therefore has a single-direction effect size (association with an increase or decrease in concentration), an arrow is used in place of the X to indicate the direction of that effect in the model.

12

Meat Type

Model BaP ChY BaA BkF BbF DahA IP BghiP PhIP MeIQx

All NA 1.5 14.7 47.0 4.5 4.7 47.0 17.1 30.9 100.0 9.8Beef 1 0.3 <0.01 6.3 99.2 5.7 64.4 1.8 5.3 31.9 3.3Beef 2 88.0 82.5 7.6 100.0 85.5 <0.01 5.4 5.3 95.2 17.7Poultry 1 0.1 19.2 23.8 99.6 21.2 97.5 71.2 0.0 39.2 36.3Poultry 2 96.2 21.9 37.7 99.6 20.3 98.3 98.0 63.5 34.2 52.7Pork 1 98.6 2.9 0.8 14.3 0.0 96.4 0.4 <0.01 3.8 1.0Pork 2 67.7 2.0 5.7 33.1 0.0 98.8 0.4 2.0 99.9 63.0Seafood 1 99.7 2.3 62.8 96.6 7.5 96.3 42.6 33.9 6.4 86.9Seafood 2 14.1 3.0 22.0 82.8 <0.01 93.3 0.0 1.1 86.1 91.7Bread NA 61.6 65.4 0.0 99.0 <0.01 99.3 99.3 6.9 NA NA

Supplemental Table 6: I2 values for each regression model and subdivided regression models for all compounds and meat types. Values are in percent, expressing the percent of heterogeneity between studies which is not due to chance.

13

Supplemental Results Appendix:

Significant predictors in HCA models

The directionality of time and temperature in HCA models were all positive if significant (Supplemental Table 5), indicating that increase in time and/or temperature at which food is cooked are associated with increased PhIP and MeIQx concentrations in all meats of at least one cooking method. The highest coefficient relating time and concentration was found in pork’s Model 2, which included barbecued and deep-fried meat (5.79, which converts to an average increase in PhIP of 5.45 nanograms per gram per minute of cooking time), followed by poultry’s Model 1 (foods not cooked by barbecuing or smoking), at 4.34 (converting to an average increase of 1.28 ng/g/min of cooking time. PhIP concentrations in fish were least influenced by cooking time, which was not significant in either fish/PhIP model. Time coefficients for MeIQx models were lower than the corresponding values for PhIP in general, the highest being that of poultry at 1.78 (0.10 ng/g/min, supplementary table 12).

In some meat types, percent of fat in the raw product, the presence of skin on the cooked meat (specifically poultry), and whether the meat was flipped at least once during preparation were also found to improve the model (Error: Reference source not found and Error: Reference source not found of the main text, and Supplemental Table 5).

Cooking method, either alone or as the interaction with form of the food, was significant in all models for PhIP and MeIQx. As discrete variables, these coefficients represent relative averages compared with the base cooking method chosen alphabetically (supplementary table 13). For example, in the case of beef, this reference category was baked pan residues/drippings, which was also the lowest cooking type/food form combination in PhIP concentration, but not in MeIQx concentration. Relative to this group, barbecued beef (ground or whole) was between 80-337 times higher in PhIP, and 4.5 times higher in MeIQx, and broiled beef was between 3 and 100 times higher, and 3-10 times lower in MeIQx. Fried beef was 48-99 times higher, and although fried whole beef was 1.5 times higher, fried ground beef was 77% of the average concentration in MeIQx. Baked pan residue/drippings was also the reference category of cooking method and food form for poultry. In this case, however, the baked drippings category was not the lowest in PhIP concentration, or in MeIQx. Broiled and roasted poultry parts were 14 times greater in PhIP, and 45 times greater in MeIQx, respectively, and barbecued parts were 4 and 5 times greater than baked residues for PhIP and MeIQx.

Pork models for PhIP did not use an interaction between cooking method and form of the food, but the Model 1 for MeIQx did and Model 2 did not, so the coefficients for the two compounds’ models differ (supplemental table 13). In the PhIP model, baking was the reference cooking method, and dripping was the reference for food forms. All of the cooking methods compared with baking were higher in PhIP concentration, barbecuing, broiling and microwaving substantially so. In the MeIQx model 1, baked drippings/pan residue are again the reference group, and the cooking method of baking was the reference group in model 2, for the methods of barbecuing and microwaving. Except when smoked, whole cuts were in general lower than the reference group (approximately 30% of the MeIQx concentration), while other cooking methods and food form combinations were higher.

Seafood models did not find the form to be significant, but rather the group of the fish. The PhIP models did not use the interaction term between the fish group and cooking method, but MeIQx models did, so that as with pork, the coefficients used in the estimation of these compounds differed. In the case of

14

these models, ‘assorted’ was the fish group reference level, and Baked was again the cooking method reference level. Barbecuing was 8 times higher than baking in MeIQx, and barbecued salmon was 135 times higher than baked fish in PhIP. The coefficient sizes for cooking methods combined with fish groups for PhIP are higher than those for the fish group or cooking method alone.

Significant Predictors in PAH Models

The directionality of the associations of concentration with time and temperature was variable among the subdivided models, with no consistent positive or negative association with time/temperature among the eight compounds. If the interaction between the two and the main effects were both present, the interaction effect often opposed the time effect directionally (Supplemental Table 5) and was of the same magnitude (supplemental table 12). Time was much more commonly a factor than temperature, and in many of the regressions the interaction of time with the percentage of raw fat was significant and negative (supplemental tables 5 and 12). Interactions between time and the use of direct flame were significant in models for DahA/Pork, BkF/Poultry, and IP/Beef, having a small but positive coefficient. In the models for PAH in bread, time and temperature were always significant, but the interaction between the two was significant only for BaP, ChY, and IP. As in the meats, the interaction’s coefficient was of the same magnitude and opposite sign of the coefficient for time in the regression (supplemental table 12).

The effect sizes of seafood, pork, beef, and poultry, i.e., the relative average value for each meat type compared to the average value for bread, respectively for DahA were 103.5, 4.7, 2.8, and 1.3, and for IP were 95.6, 4.06, 1.3, and 0.85), and BghiP (effect sizes were 0.60, 0.5, 1.3 0.45). In general, shellfish were associated with higher PAH concentrations of all types (Supplemental Table 5). The relatively high effect sizes for raw preparations in fish models can be attributed to the shellfish preparations. In models for bread, toasting and grilling already-baked breads both were associated with higher average concentrations for all PAHs except in the case of BaP/Toasting, BkF/Toasting, and BghiP/Toasting and BghiP/Grilling. The increase from these additional cooking methods was greater for grilled breads (ranging from 4 times the concentration in baked bread for BaP to 86 times the concentration for IP) than for toasted (1.4 times in BaA to 23 times in IP).

As with HCA models, the cooking method and food form, and/or some interaction between the two, was used in most of the models (Supplementary table 14). Exceptions were most often poultry or seafood models. Where cooking methods were a predictive variable, barbecued foods and baked foods were the reference groups. Barbecued meats of all types were in general associated highest in BaP and BaA concentration when compared with other cooking methods, although the degree to which the coefficients were higher varied between 4 times greater to 268 times greater than the lowest cooking method effect size within the same model, and in some cases, were lower than smoked foods’ effect sizes (smoked beef was 9 times higher than barbecued, in BaP concentration, and 3 times higher in pork). Aside from barbecued foods, smoked meats tended to be higher in most PAH effect sizes than other cooking methods by 3 to 33 times. In the ChY and BkF models, smoked meats were higher than the reference categories by 2 to 5 times (ChY) and in some cases, e.g. smoked fish, 60,000 times (BkF), with generally higher effect sizes than barbecued foods. Broiled meats also produced relatively high effect sizes, and were the highest associated mean concentrations in some models. The variable nature of these effect sizes and in some cases, very large magnitudes limits their generalized interpretation, particularly without the context of the model and stratified modeling approach.

15

For foods cooked with sources of flame and smoke (barbecued and smoked foods), the flame’s source of fuel was frequently significant as was the interaction between the fuel source and cooking time. In other words, the impact of cooking time varied according to the way the smoke or flame was produced (Supplemental Table 5). The larger the coefficient of the main effect of fuel type, however, the lower the corresponding coefficient for the interaction of the fuel with time was. In all cases except BghiP in beef, lump charcoal or charcoal and wood as a fuel source was associated with the highest mean concentrations in comparison with charcoal briquettes, ranging from 4 to 160,000 times higher.

16

Model 1: BeefStudy Variance 1.082Fixed Effects: β SE

Intercept 4.24E-11 5.77487Cooking Method X Form of Food

BakedWhole 1 0

BoiledDrippings 2.9E-05 23.90

FriedGround 8.1E+01 3.83Whole 7.8E+01 4.09

RawGround 5.2E-12 3433.21Whole 6.7E-12 3329.18

RoastedDrippings 2.3E+00 2.57

Whole 4.6E+00 2.16Smoked

Ground 2.6E-03 13.07Time * exp(-1/Temp) 3.8E-133 2.8E+86Time (hours) 2.4E+133 1.8E+87Temp (Kelvin) 8.4E-01 1.05

Model 2: BeefStudy Variance 4.013Fixed Effects: β SE

Intercept 0.03 7.42Cooking Fuel

Charcoal 11.33 4.16Charcoal + Wood 13.23 4.19

Electric 1.12 2.96Gas 1.49 3.27

Wood 0.21 8.04Food form

Ground 0.92 4.73Whole 1.18 2.60

Cooking MethodBarbecued 14.34 2.23

Boiled 1.10 4.93Broiled 0.10 2.63

Fried 0.73 2.21Raw 3.70 3.07

Roasted 2.87 2.13Cooking Method X Form of Food

17

Barbecued Ground 19.78 3.49Boiled Whole 1.21 3.99

Broiled Ground 4.42 4.18Fried Ground 1.29 3.52

Cooking Fuel X Time (hours)Time over Briquettes 41.52 76.82

Time over Charcoal 5.81 180.72Time over Charcoal + Wood 0.17 103.29

Time over Electric 0.56 1.38Time over gas 2.59 4.37

Supplemental Table 7: Fixed effect coefficients and associated standard errors for two models of BaP concentration in beef. The first model was fit and used to estimate data for those cooking types where time and temperature data were complete. The second model was fit to the full dataset but used for those cooking categories where temperature and some time data was not reported. Coefficients for models other than BaP are available on request.

Model 1: PoultryStudy Variance 4.986Fixed Effects: β SE

Intercept 0.00077 11.59Cooking Method X Form of Food

BoiledWhole 42.54 5.12

Part 173.73 3.02Fried

Part 131.16 4.87Indirect Smoked

Part 0.00003 909.46Raw

Part 197.84 5.57Whole 526.20 5.68

RoastedDrippings 16.29 4.55

Part 66.49 3.69Whole 259.73 4.38

SmokedPart 1748.18 2.37

Whole 26.68 4.97Time (hours) 26831.56 1.15E+33Temperature (Kelvin) 1.00 1.01Time * exp(-1/Temp) 0.0001 7.05E+32Cooking Fuel X Percent of Fat

Percent of Fat over Electric 0.87 1.04Percent of Fat over Wood 0.92 1.04

18

Model 2: PoultryStudy Variance 4.986Fixed Effects: β SE

Intercept 0.02 3.29Form of Food

Drippings 1 0Part 48.44 1.95

Whole 39.49 1.99Time (hours) 0.93 1.03Cooking Fuel X Percent of Fat

Percent of Fat over Briquettes 0.87 1.03Percent of Fat over Charcoal 0.92 1.01Percent of Fat over Charcoal + Wood 0.96 1.03Percent of Fat over Electric 0.74 1.02Percent of Fat over Gas 0.90 1.02Percent of Fat over Wood 1.04 1.02

Supplemental Table 8: Fixed effect coefficients and associated standard errors for two models of BaP concentration in poultry. The first model was fit and used to estimate data for those cooking types where time and temperature data were complete. The second model was fit to the full dataset but used for those cooking categories where temperature and some time data was not reported. Coefficients for models other than BaP are available on request.

Model 1: PorkStudy Variance 3.9Fixed Effects: β SE

Intercept 3.87E-04 5.21Cooking Method

Baked 1 0Broiled 0.28 3.34Dried 0.55 3.22Fried 2.85 3.06Indirect Smoked 0.27 3.61Microwaved 0.76 4.05Raw 15.84 3.91Smoked 1.86 3.17

Food FormDrippings 1 0Ground 23.56 2.20Slice 12.90 2.26Whole 54.58 2.29

Time (hours) 1.19E-18 3.73E+20Time * exp(-1/Temp) 8.36E+17 2.66E+20

Cooking Fuel X Time (hours)Time over Electric Heat 2.06 1.42

19

Model 2: PorkStudy Variance 2.584Fixed Effects: β SE

Intercept 9.41E-02 5.21Cooking Method

Baked 1 0Barbecued 1.126 2.108Broiled 0.010 2.024Dried 0.020 2.101Fried 0.084 1.919Indirect Smoked 0.001 2.785Microwaved 0.026 2.597Raw 0.348 2.391Roasted 0.008 2.132Smoked 1.428 3.280

Food FormDrippings 1 0Ground 26.86 2.14Slice 9.28 2.25Whole 25.94 2.19

Cooking FuelBriquettes 1 0Charcoal 2.797 1.649Charcoal+Wood 15.020 1.649Electric 0.195 1.757Gas 0.206 1.649Wood 0.010 3.445

Supplemental Table 9: Fixed effect coefficients and associated standard errors for two models of BaP concentration in pork. The first model was fit and used to estimate data for those cooking types where time and temperature data were complete. The second model was fit to the full dataset but used for those cooking categories where temperature and some time data was not reported. Coefficients for models other than BaP are available on request.

Model 1: SeafoodStudy Variance 4.226Fixed Effects: β SE

Intercept 1.51E+00 5.21Cooking Method X Food Form

Baked Fillet 1 0Broiled Fillet 295.01 630.8Fried Fillet 1.39 2.17E+14Indirect Smoked Whole 0.20 4.02E+11Raw Fillet 34891.6 3.95E+14

SmokedFillet 33.95 42.69

20

Whole 30.23 43.21Time * exp(-1/Temp) 3.67E-116 9.38E+140Time(hours) 3.00E+116 5.12E+142Temp (Kelvin) 1.05 1.39

Cooking FuelBriquettes 1 0Gas 24.00 4.11Wood 0.99 2.79

Model 2: SeafoodStudy Variance 5.16Fixed Effects: β SE

Intercept 1.292 3.843Cooking Method

Barbecued 1 0Boiled 0.012 3.623Broiled 0.360 3.370Fried 0.212 3.872Indirect Smoked 0.001 3.360Raw 0.186 4.611Smoked 2.671 4.625

Time(hours) 0.096 2.142Cooking Fuel

Briquettes 1Charcoal 1.838 1.788Charcoal + Wood 3.554 1.836Electric 0.336 4.241Gas 5.049 1.948Wood 1.300 2.511

% Fat in Raw Fish 1.057 1.101Type of Fish

Not fish 1 0Herring 7.255 1.901Cod 1.081 2.821Perch 4.707 2.327Salmon 1.642 1.764Shellfish 6.380 2.991

Supplemental Table 10: Fixed effect coefficients and associated standard errors for two models of BaP concentration in seafood. The first model was fit and used to estimate data for those cooking types where time and temperature data were complete. The second model was fit to the full dataset but used for those cooking categories where temperature and some time data was not reported. Coefficients for models other than BaP are available on request.

Model: BreadStudy Variance 0.9868

21

Fixed Effects: βIntercept 0.12 4.76Cooking Method

Baked 1Grilled 4.084 4.572Toasted 0.070 4.576

Time(hours) 1.84E+22 45177918.65Temp (Kelvin) 1.03 1.002Time * exp(-1/Temp) 3.14E-22 34040787.64

Supplemental Table 11: Fixed effect coefficients and associated standard errors for the model of BaP concentration in bread. Coefficients for models other than BaP are available on request.

Supplemental Example 1: Dietary exposure calculation using this data

Potential exposure to PhIP from a hypothetical portion of barbecued chicken:

Portion size for a barbecued chicken thigh: 65g (95% CrI: 64.5, 65.5)Average concentration of PhIP in barbecued chicken: 21.4 ng/g (95% CrI: 16.5, 26.3)

Deterministic Estimated Exposure: 65 g × 21.4 ng/g = 1.39 g PhIP in one barbecued chicken thighEstimated Exposure Mean with Uncertainty: 1) Standard Errors of the Mean:

a) Chicken mass: (65-64.5)/1.96 = 0.26b) PhIP Concentration: (21.4-16.5)/1.96 = 2.51

2) Probabilistic Estimated Exposure: (65, 0.26) × (21.4, 2.51): 1.39 g (95% CrI: 1.38, 1.39)

22

Compound Meat Predictor Mean Coefficients

(Model 1, Model 2)Converted coefficients (Model 1, Model 2)

PhIP All Time 1.58 4.85 ng/g/minPhIP All Temp 0.02 1.02 ng/g/°CPhIP All Skin -0.73 52% reduction in skin-onPhIP All Oiled Pan -0.42 34% reduction with oiled panMeIQx All Time 0.32 1.38 ng/g/minMeIQx All Temp 0.01 1.01 ng/g/°CMeIQx All Skin -0.89 59% or 40% decrease with skin-onPhIP Beef Time 1.35, 1.52 0.06 ng/g/min, 0.08 ng/g/minPhIP Poultry Time 4.34, 3.47 1.28 ng/g/min, 0.54 ng/g/minPhIP Pork Time --, 5.79 5.45 ng/g/minMeIQx Beef Time 0.37, 0.43 1.45 ng/g/min, 1.54 ng/g/minMeIQx Poultry Time 1.78, 1.67 5.93 ng/g/min, 5.31 ng/g/minMeIQx Seafood Time 8.52, 5.014 g/g/minPhIP Beef Temp 0.03, -- 1.03 ng/g/°CPhIP Pork Temp --, 0.01 1.04 ng/g/°CPhIP Seafood Temp 0.04, -- 1.02 ng/g/°CMeIQx Beef Temp 0.02, -- 1.04 ng/g/°CMeIQx Pork Temp 0.04, -- 1.04 ng/g/°CMeIQx Poultry Temp 0.006, 1.01 ng/g/°CMeIQx Seafood Temp 0.03, -- 1.03 ng/g/°CPhIP Beef Time and Temp 9.87, -- 19341.3 ng/g/minMeIQx Poultry Time and Temp 5.65, 5.48 284.3 ng/g/minMeIQx Seafood Time and Temp 2.22, -- 9.21 ng/g/minPhIP Beef Fat % 0.06, 0.13 1.06 ng/g/% mass, 1.54 ng/g/% massMeIQx Seafood Fat % 0.54, 0.59 1.72 ng/g/% mass, 1.80 ng/g/% massPhIP Poultry Skin -0.40, -0.32 33%, 27% reduction in skin-onMeIQx Poultry Skin -0.66, -0.63 48%, 47% reduction in skin-onPhIP Pork Oiled Pan -2.65, -- 93% reduction with oiled panMeIQx Pork Oiled Pan 0.88,-0.85 141% increase with oiled pan or 57% decreasePhIP Pork Flipped 0.75, -- 112% increase with flipMeIQx Pork Flipped -0.33, 0.31 28% decrease or 36% increase with flipMeIQx Beef Fat% and Temp 0.00, -- 1.03 ng/g/°C * % massBaP Bread Time 51.27 1.84E22 ng/g/minBaP Bread Temp 0.03 1.03 ng/g/°CBaP Bread Time and Temp -49.51 3.14E-22 ng/g/minChY Bread Time -11.96 6.38E-06 ng/g/minChY Bread Temp 0.00 1.00 ng/g/°CChY Bread Time and Temp 13.77 956372.7 ng/g/minBaA Bread Time 3.66 39.0 ng/g/minBaA Bread Temp 0.02 1.02 ng/g/°CBkF Bread Time 5.51 247.5 ng/g/min

23

BkF Bread Temp 0.03 1.03 ng/g/°CBbF Bread Time 4.14 62.5 ng/g/minBbF Bread Temp 0.02 1.02 ng/g/°CDahA Bread Time 4.35 77.5 ng/g/minDahA Bread Temp 0.00 1.00 ng/g/°CIP Bread Time -68.06 2.75E-30 ng/g/minIP Bread Temp 0.01 1.01 ng/g/°CIP Bread Time and Temp 74.31 1.87E32 ng/g/minBghiP Bread Time -7.08 0.0008 ng/g/minBghiP Bread Temp 0.00 1.00 ng/g/°CBaP Beef Time 357.35, -- 1.57E155 ng/g/minBaP Beef Temp -0.16, -- 0.85 ng/g/°CBaP Beef Time and Temp -354.79, -- 8.25E-155 ng/g/minChY Beef Time 112.09, 1.79 4.79E48 ng/g/min, 5.98 ng/g/minChY Beef Time and Temp -112.09, -- 2.09E-49 ng/g/minChY Beef %Fat 0.09, 0.12 1.09 ng/g/ % mass, 1.13 ng/g/ % massBaA Beef Time --, 1.70 5.47 ng/g/minBaA Beef Time and Temp --, -1.14 0.32 ng/g/min

BaA Beef%Fat with Flame --, -0.02 0.98 ng/g/ % mass with flame

BkF BeefTime and Temp (Baked) 0, -- 1.00 ng/g/min

BkF BeefTime and Temp (BBQ) 5.56, -- 259.8 ng/g/min

BkF BeefTime and Temp (Fried) -5.46, -- 0.004 ng/g/min

BkF BeefTime and Temp (Roasted) -2.45, -- 0.086 ng/g/min

BkF Beef %Fat --, 0.18 1.20 ng/g/minBbF Beef Time and Temp 1.37, -- 3.94 ng/g/minBbF Beef Time --, -1.75 0.17 ng/g/minBbF Beef Flame --, 4.58 97.51 increase with flameDahA Beef Time -0.81 0.44 ng/g/minIP Beef Time -1.24,-- 0.29 ng/g/min

IP BeefTime with Flame --, 0.90 2.46 ng/g/min

BghiP Beef Time 11.39 88433 ng/g/minBghiP Beef Temp 0.002 1.00 ng/g/°CBghiP Beef Time and Temp -10.80 2.04E-05 ng/g/minBghiP Beef %Fat -0.10 0.90 ng/g/ % massBaP Poultry Time 10.20, -0.07 26903 ng/g/min, 0.93 ng/g/minBaP Poultry Temp -0.004, -- 1.00 ng/g/°CBaP Poultry Time and Temp -9.54, -- 7.19E-05 ng/g/minChY Poultry Time 0.23, -0.23 1.26 ng/g/min, 0.79 ng/g/minChY Poultry %Fat -0.04, -0.08 0.96 ng/g/ % mass, 0.92 ng/g/ % mass

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BaA Poultry Time 0.05, -0.05 1.05 ng/g/min, 0.95 ng/g/minBaA Poultry %Fat -0.09, -0.20 0.91 ng/g/ % mass, 0.82 ng/g/ % mass

BkF PoultryTime with Flame 0.68, -- 1.97 ng/g/min

BkF Poultry Time and %Fat --, -0.03 0.97 ng/g/ % mass * minBbF Poultry Time 0.14, 1.84 1.15 ng/g/min, 6.30 ng/g/minBbF Poultry %Fat -0.85, -0.11 0.43 ng/g/ % mass, 0.90 ng/g/ % massBbF Poultry Time and %Fat --, -0.18 0.84 ng/g/ % mass * minDahA Poultry %Fat --, 0.08 1.08 ng/g/ % massIP Poultry Time 0.02, 0.96 1.02 ng/g/min, 2.59 ng/g/minIP Poultry %Fat --, 0.15 1.16 ng/g/ % massIP Poultry Time and %Fat --, -0.09 0.91 ng/g/ % mass * minBghiP Poultry Time 238.8, 0.44 5.12E103 ng/g/min, 1.55 ng/g/minBghiP Poultry Time and Temp -235.77, -- 4.04E-103 ng/g/minBghiP Poultry Flame 0.99, -- 2.69 ng/g with flame useBghiP Poultry %Fat --, 0.05 1.05 ng/g/ % massBghiP Poultry Time and %Fat --, -0.04 0.96 ng/g/ % mass * minBaP Pork Time -41.27, -- 1.1E-18 ng/g/minBaP Pork Time and Temp 41.27, -- 8.38E17 ng/g/minChY Pork Time --, -1.36 0.26 ng/g/minBkF Pork Time --, -1.93 0.15 ng/g/minBbF Pork Time --, -2.27 0.10 ng/g/minBbF Pork Time and Temp 2.27, -- 9.68 ng/g/minDahA Pork Time -0.85, -0.82 0.43 ng/g/min, 0.44 ng/g/minDahA Pork Flame --, 0.99 2.69 ng/g with flame use

DahA PorkTime with Flame --, 0.19 1.21 ng/g/ % mass with flame use

IP Pork Time -1.01, -1.66 0.36 ng/g/min, 0.19 ng/g/minBghiP Pork Time -0.35, -- 0.70 ng/g/minBaP Seafood Time 268.2, -2.39 3.01E116 ng/g/min, 0.09 ng/g/minBaP Seafood Temp 0.0047, -- 1.00 ng/g/°CBaP Seafood Time and Temp -265.8, -- 3.67E-116 ng/g/minBaP Seafood %Fat --, 0.06 1.06 ng/g/ % massChY Seafood %Fat 0.13, -- 1.14 ng/g/ % massBaA Seafood Time 0.31, -2.40 1.36 ng/g/min, 0.09ng/g/minBkF Seafood Time -0.60, -0.23 0.55 ng/g/min, 0.79 ng/g/minBkF Seafood Temp 0.29, -- 1.34 ng/g/°CBbF Seafood Time -1.30, -- 0.27 ng/g/minBbF Seafood %Fat 0.16, -- 1.17 ng/g/ % massDahA Seafood Time -0.31, 1.02 0.73 ng/g/min, 2.77 ng/g/minIP Seafood Time -0.25, 0.55 0.78 ng/g/min, 1.73 ng/g/min

Supplemental Table 12: Regression coefficients for continuous and binary variables from Model 1s and Model 2s per compound and meat type. Converted coefficients represent the exponentiated coefficient, as converted into the stated units (e.g., the hourly coefficient divided by 60 to yield the rate in minutes).

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Meat MethodForm/Fish group

PhIP exp(β)

MeIQx exp(β)

Beef Baked Dripping 1.00 1.00Beef Fried Dripping 83.16 0.55Beef Baked Whole 9.16 0.72Beef Barbecued Whole 337.15 4.53Beef Broiled Whole 99.88 0.11Beef Fried Whole 99.48 1.43Beef Microwaved Whole 5.58 1.11Beef Baked Ground 1.13 0.33Beef Barbecued Ground 80.56 4.53Beef Broiled Ground 3.12 0.04Beef Fried Ground 48.05 0.77Poultry Baked Dripping 1.00 1.00Poultry Fried Dripping 0.79 4.93Poultry Baked Part 0.05 0.60Poultry Broiled Part 14.11 5.61Poultry Deep Fried Part 1.65 1.48Poultry Fried Part 3.50 4.04Poultry Roasted Part 0.23 45.02Poultry Baked Whole 0.07 1.48Poultry Boiled Whole 0.00 0.11Poultry Roasted Whole 0.01 3.98Poultry Barbecued Part 4.60 5.11Poultry Microwaved Part 0.09 0.35Pork Baked All 1.00 --Pork Barbecued All 580552.78 --Pork Broiled All 488.04 --Pork Fried All 7.42 --Pork Microwaved All 10094.41 --Pork Smoked All 1.69 --Pork All Dripping 1.00 --Pork All Whole 0.13 --Pork All Ground 0.02 --Pork All Sliced 0.07 --Pork Baked Drippings -- 1.00Pork Baked Whole -- 0.29Pork Fried Whole -- 0.36Pork Smoked Whole -- 3.13Pork Fried Ground -- 1.46Pork Broiled Slice -- 2.58Pork Fried Slice -- 3.19Pork Smoked Slice -- 0.42Pork Baked All -- 1.00Pork Barbecued All -- 3.88

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Pork Microwaved All -- 4.67Seafood Baked All 1.00 1.00Seafood Fried All 1.19 1.11Seafood Barbecued All -- 7.72Seafood Microwaved All -- 0.11Seafood All Assorted 1.00 1.00Seafood All Herring 0.16 0.12Seafood All Cod 1.14 8.92Seafood All Perch 1.07 1.88Seafood All Salmon 1.44 2.99Seafood All Shellfish 0.08 2.28Seafood Baked Assorted 1.00 --Seafood Fried Assorted 12.09 --Seafood Fried Herring 2.65 --Seafood Fried Cod 11.56 --Seafood Baked Perch 8.61 --Seafood Fried Perch 11.77 --Seafood Baked Salmon 5.15 --Seafood Barbecued Salmon 135.23 --Seafood Fried Salmon 23.63 --Seafood Microwaved Salmon 0.45 --

Supplemental Table 13: Effect sizes and exponentiated effect sizes, representing the average multiplicative value compared with the reference level, for the levels of discrete predictive variables of cooking method, food form, and fish group for the HCA regressions.

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BaP ChY BaA BkF BbF DahA IP BghiP

Meat MethodForm/Fish group β exp(β) β

exp(β) β exp(β) β exp(β) β exp(β) β exp(β) β exp(β) β exp(β)

Bread Baked All 0.00 1.00 0.00 1.00 0.00 1.00 0.00 1.00 0.00 1.00 0.00 1.00 0.00 1.00 0.00 1.00Bread Grilled All 1.41 4.08 1.55 4.71 2.71 15.04 3.83 46.25 2.95 19.06 2.63 13.92 4.46 86.71 -3.85 0.02Bread Toasted All -2.66 0.07 0.80 2.23 0.34 1.40 -0.28 0.76 0.37 1.44 1.79 6.00 3.13 22.93 -4.85 0.01Beef Baked Ground 0.00 1.00 0.00 1.00 0.00 1.00Beef Boiled Drippings -10.00 0.00

Beef Boiled Whole -10.130.0000

4 Beef Broiled Ground 2.28 9.81 2.95 19.18 Beef Broiled Whole 1.13 3.11 2.95 19.11

Beef Fried Ground 3.34 28.27 -3.54 0.03 -5.81 0.003 -3.49 0.03-

4.27 0.01 -2.13 0.12

Beef Fried Whole 3.63 37.65 -3.54 0.03 -7.33 0.001 -3.49 0.03-

4.42 0.01 -4.55 0.01

Beef Raw Ground -25.12 0.000 -2.45 0.09 -5.72 0.003 -2.55 0.08-

3.44 0.03 -1.48 0.23

Beef Raw Whole -24.86 0.000 -2.45 0.09 -6.16 0.002 -2.55 0.08-

2.38 0.09 -0.94 0.39Beef Roasted Drippings 0.89 2.43 -3.68 0.03 -0.33 0.72

Beef Roasted Whole 0.86 2.36 -3.68 0.03 -5.85 0.003 -

3.56 0.03 -3.43 0.03Beef Smoked Ground -9.15 0.000 2.19 8.92 -0.32 0.73 -0.34 0.71Beef Barbecued Ground 0.00 1.00 0.00 1.00 0.00 1.00 0.00 1.00 0.00 1.00 1.77 5.85

Beef Barbecued Whole -5.21 0.01 -2.51 0.08 -2.45 0.09 -5.77 0.003-

5.21 0.01 -2.55 0.08Beef Broiled Ground 0.72 2.04 -0.26 0.77 4.95 141.17 3.11 22.47 0.72 2.04

Beef Fried Ground -3.77 0.02 -5.72 0.003 -2.15 0.12 -0.15 0.86-

3.77 0.02

Beef Fried Whole -3.89 0.02 -7.15 0.001 -0.62 0.54 -

3.89 0.02

Beef Raw Ground -2.42 0.09 -6.09 0.002 -1.01 0.37 -

2.42 0.09

Beef Raw Whole -1.36 0.26 -5.72 0.003 -1.45 0.24 -

1.36 0.26 Beef Roasted Whole -3.77 0.02 -5.35 0.005 - 0.02

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3.77Poultry Baked Part 0.00 1.00 0.00 1.0 0.00 1.00 0.00 1.00 0.00 1.00Poultry Boiled Whole 3.75 42.54 Poultry Broiled Part 5.16 173.73 Poultry Fried Part 4.88 131.23 7.00 1100.0 2.12 8.33 0.44 1.55 3.18 24.04Poultry Raw Part 5.29 197.84 9.35 11477.0 3.09 22.09 2.05 7.74 6.04 418.17Poultry Raw Whole 6.27 526.20 9.63 15176.4 0.42 1.52 6.04 418.17Poultry Roasted Drippings 2.79 16.29 Poultry Roasted Part 4.20 66.49 8.45 4658.3 2.04 7.70 1.03 2.81 3.26 26.00Poultry Roasted Whole 5.56 259.73 6.79 891.0 1.40 4.06 3.01 20.31

Poultry Smoked Part 7.471748.1

8 15.7

36753692.

8 -7.21 0.00 5.02152.1

0 -5.15 0.01

Poultry Smoked Whole 3.28 26.68 7.99 2963.1 -

3.16 0.04 Pork Baked All 0.00 1.00 0 1.00 0.00 1.000 0.00 1.000 0.00 1.00 0.00 1.00 0.00 1.00Pork Broiled All -1.29 0.28 -0.76 0.47 Pork Dried All -0.59 0.55 Pork Fried All 1.05 2.85 -1.00 0.369 -1.55 0.212 -1.43 0.24 0.00 1.00 1.74 5.69 -1.96 0.14

PorkMicrowaved All 0.28 1.32

Pork Raw All 2.76 15.84 0.91 2.49 0.24 1.277 -1.22 0.295 -1.42 0.24 -0.41 0.66 1.52 4.59 -0.36 0.70Pork Smoked All 0.62 1.86 0.39 1.48 0.50 1.650 3.06 21.221 2.92 18.59 -0.33 0.72 2.19 8.90 -0.20 0.82Pork All Drippings 0.00 1.00 0.00 1.00 Pork All Ground 3.16 23.56 Pork All Slice 2.56 12.90 1.19 3.29 Pork All Whole 4.00 54.58 -2.22 0.11 Pork Baked All 0.00 1.00 Pork Barbecued All 0.12 1.13 0.00 1.000 0.00 1.00 0.00 1.00 Pork Roasted All -4.80 0.01 -4.44 0.012 -3.70 0.02 -1.87 0.15 Pork Smoked All 0.36 1.43 0.21 1.234 0.36 1.43 -0.62 0.54 Pork Fried All -4.69 0.01 -2.14 0.12 Pork Dried All -1.58 0.207 -3.71 0.02 -3.11 0.04 Fish Baked All 0.00 1.00 0.00 1.00 0.00 1.00Fish Broiled All 5.69 295.01 Fish Fried All 0.33 1.39 -3.19 0.04 -2.92 0.05 -2.56 0.077 -4.22 0.01 0.32 1.38 -4.63 0.01Fish Raw All 0.10 1.11 -4.64 0.01 3.99 54.05 0.37 1.45 -0.40 0.67

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Fish Smoked All 3.53 33.95 1.77 5.85 7.752321.

6 -1.96 0.141 3.51 33.3911.4

392042.

0Fish Barbecued All 0.00 1.00 0.00 1.00 0.00 1.00 0.00 1.000 0.00 1.00 0.00 1.00 Fish Boiled All -5.58 0.00 1.12 3.05 3.01 20.22 -0.98 0.37

Fish Smoked All 1.03 2.81 11.4

5 93901.3 13.65847460.9

2 -0.55 0.58 Fish All Assorted 0.00 1.00 0.00 1.00 0.00 1.00 0.00 1.00 0.00 1.00Fish All Herring 1.64 5.15 -2.96 0.05 0.69 1.99 1.26 3.51 0.12 1.13Fish All Cod -0.21 0.81 -3.39 0.03 -0.73 0.48 Fish All Perch 1.04 2.83 -2.86 0.06 0.61 1.83 1.07 2.92 0.27 1.31

Fish All Salmon 0.01 1.01 -4.56 0.01 -5.91 0.00 -

0.01 0.99 -0.32 0.73Fish All Shellfish 1.44 4.23 2.87 17.65

Supplemental Table 14: Effect sizes and exponentiated effect sizes, representing the average multiplicative value compared with the reference level, for the levels of discrete predictive variables of cooking method, food form, and fish group for the PAH regressions.

30