efsa-opinion-chromium-food-drinking-water
efsa-opinion-chromium-food-drinking-water efsa-opinion-chromium-food-drinking-water
Chromium in food and bottled water LVM E4---- log-logist -- -- logistic -- -- 0.0 0.3 0 2 4 6 8 LVM H2---- 0 2 4 6 8 0.0 0.3 0 2 4 6 8 one-stage -- -- 0.0 0.3 0 2 4 6 8 two-stage -- -- 0.0 0.3 0.0 0.3 0.0 0.3 Weibull -- -- 0 2 4 6 8 0 2 4 6 8 log-prob -- -- 0.0 0.3 0 2 4 6 8 gamma -- -- 0.0 0.3 0.0 0.3 probit -- -- 0.0 0.3 0 2 4 6 8 0 2 4 6 8 0 2 4 6 8 a) Result of PROAST for all models Weibull Model, with BMR of 10% Extra Risk for the BMD and 0.95 Lower Confidence Limit for the BMDL 0.6 Weibull BMD Lower Bound 0.5 0.4 Fraction Affected 0.3 0.2 0.1 0 16:35 01/20 2014 BMDL BMD 0 1 2 3 4 5 6 7 8 9 dose b) Result of BMDS when pooling the data of males and female for Weibull model Figure J9: Fit of all models to the dose-response data on the incidence of epithelial carcinoma or adenoma combined in the duodenum, jejunum or ileum in male and female mice combined. Note that the models denoted LVM E2 and H3 are not recommended by EFSA (2009c). EFSA Journal 2014;12(3):3595 238
Chromium in food and bottled water The BMD calculations for epithelial carcinoma or adenoma in the duodenum, jejunum or ileum in male and female mice were based on the number of animals initially in study (n = 50; see Witt at al., 2013). A sensitivity analysis showed no difference when accounting for early death and drop put as reported by NTP ( BMDL 10 = 0.99) and a slight decrease when accounting for intercurrent mortality based on the method used by NTP for the poly –k test (BMDL 10 = 0.89). When considering the terminal incidences only as reported by NTP the BMDL 10 was obtained as 0.79 mg/kg b.w. per day. Table J10: Epithelial carcinoma in the duodenum, jejunum or ileum carcinoma in male mice. The benchmark dose (BMD 10 ) and the 95 % benchmark dose lower confidence limit (BMDL 10 ) values are given for a BMR of 10 % extra risk with characteristics of the model fit. The model with lowest BMDL 10 is highlighted in bold. Models Restriction N of parameters Minus Loglikelihood P- value Accepted BMD 10 (mg/kg b.w. per day) BMDL 10 (mg/kg b.w. per day) Full model na 5 40.90 – – – – Null (reduced) model na 1 45.11 - - - - Probit na 2 42.42 0.39 yes 6.26 4.35 LogProbit none 2 41.41 0.79 yes 7.54 2.53 Logistic na 2 42.47 0.37 yes 6.28 4.53 LogLogistic none 2 41.38 0.81 yes 7.03 2.61 Quantal-Linear na 2 42.09 0.50 yes 5.89 3.05 Multistage Cancer na 2 42.09 0.50 yes 5.89 3.05 Multistage yes 2 41.86 0.38 yes 5.89 3.05 Weibull none 2 41.38 0.81 yes 6.94 2.63 Gamma none 2 41.36 0.81 yes 6.87 2.65 na: not applicable; b.w.: body weight. LogProbit LogProbit Model with 0.95 Confidence Level 0.2 Fraction Affected 0.15 0.1 0.05 0 16:47 06/11 2013 BMDL 0 1 2 3 4 5 6 7 dose BMD Figure J10: Fit of the logprobit model to the dose-response data on epithelial carcinoma in the duodenum, jejunum or ileum in male mice EFSA Journal 2014;12(3):3595 239
- Page 187 and 188: Chromium in food and bottled water
- Page 189 and 190: Chromium in food and bottled water
- Page 191 and 192: Chromium in food and bottled water
- Page 193 and 194: Chromium in food and bottled water
- Page 195 and 196: Chromium in food and bottled water
- Page 197 and 198: Chromium in food and bottled water
- Page 199 and 200: Chromium in food and bottled water
- Page 201 and 202: Chromium in food and bottled water
- Page 203 and 204: Chromium in food and bottled water
- Page 205 and 206: Chromium in food and bottled water
- Page 207 and 208: Chromium in food and bottled water
- Page 209 and 210: Chromium in food and bottled water
- Page 211 and 212: Chromium in food and bottled water
- Page 213 and 214: Chromium in food and bottled water
- Page 215 and 216: Chromium in food and bottled water
- Page 217 and 218: Chromium in food and bottled water
- Page 219 and 220: Chromium in food and bottled water
- Page 221 and 222: Chromium in food and bottled water
- Page 223 and 224: Chromium in food and bottled water
- Page 225 and 226: Chromium in food and bottled water
- Page 227 and 228: Chromium in food and bottled water
- Page 229 and 230: Chromium in food and bottled water
- Page 231 and 232: Chromium in food and bottled water
- Page 233 and 234: Chromium in food and bottled water
- Page 235 and 236: J.1.2. mice Chromium in food and bo
- Page 237: Chromium in food and bottled water
- Page 241 and 242: Chromium in food and bottled water
- Page 243 and 244: Chromium in food and bottled water
- Page 245 and 246: Chromium in food and bottled water
- Page 247 and 248: Chromium in food and bottled water
- Page 249 and 250: Chromium in food and bottled water
- Page 251 and 252: Chromium in food and bottled water
- Page 253 and 254: Chromium in food and bottled water
- Page 255 and 256: Chromium in food and bottled water
- Page 257 and 258: Chromium in food and bottled water
- Page 259 and 260: Chromium in food and bottled water
- Page 261: Chromium in food and bottled water
Chromium in <strong>food</strong> and bottled <strong>water</strong><br />
LVM E4----<br />
log-logist -- --<br />
logistic -- --<br />
0.0 0.3<br />
0 2 4 6 8<br />
LVM H2----<br />
0 2 4 6 8<br />
0.0 0.3<br />
0 2 4 6 8<br />
one-stage -- --<br />
0.0 0.3<br />
0 2 4 6 8<br />
two-stage -- --<br />
0.0 0.3<br />
0.0 0.3<br />
0.0 0.3<br />
Weibull -- --<br />
0 2 4 6 8<br />
0 2 4 6 8<br />
log-prob -- --<br />
0.0 0.3<br />
0 2 4 6 8<br />
gamma -- --<br />
0.0 0.3<br />
0.0 0.3<br />
probit -- --<br />
0.0 0.3<br />
0 2 4 6 8<br />
0 2 4 6 8<br />
0 2 4 6 8<br />
a) Result of PROAST for all models<br />
Weibull Model, with BMR of 10% Extra Risk for the BMD and 0.95 Lower Confidence Limit for the BMDL<br />
0.6<br />
Weibull<br />
BMD Lower Bound<br />
0.5<br />
0.4<br />
Fraction Affected<br />
0.3<br />
0.2<br />
0.1<br />
0<br />
16:35 01/20 2014<br />
BMDL BMD<br />
0 1 2 3 4 5 6 7 8 9<br />
dose<br />
b) Result of BMDS when pooling the data of males and female for Weibull model<br />
Figure J9: Fit of all models to the dose-response data on the incidence of epithelial carcinoma or<br />
adenoma combined in the duodenum, jejunum or ileum in male and female mice combined. Note that<br />
the models denoted LVM E2 and H3 are not recommended by EFSA (2009c).<br />
EFSA Journal 2014;12(3):3595 238
Change language