efsa-opinion-chromium-food-drinking-water

Chromium in food and bottled water
these data and back-calculating them to the original scale. It should be also noted that the graphs of
PROAST software present the 95 % confidence interval of the means using the lognormal distribution
such that the whiskers in the graphic do not indicate the range of the data or the range between
plus/minus the standard deviation or standard errors of the mean but a 95 % confidence interval.
For quantal data PROAST implemented the multistage models as nested model family and allows such
the selection of a best fitting model in that family. Therefore, the best fitting model in this nested family
and its BMD/L pair were assessed together with the BMD/L pairs of the other models.
When the observed dose response curves for males and females exhibited a high degree of similarity,
when the dose ranges were by design identical or at least comparable and when the means was
comparable in both sexes, a combined BMD modeling of the male and female dose-response data using
sex as covariate was performed using the PROAST software. It should be also noted that PROAST
software automatically tests for a statistically significant difference between the two sexes (based on the
fitted models and model parameter values). When there is no statistical significant difference (p > 0.05)
the data are pooled into one data set and the resulting BMD/L values of that analysis is reported.
Therefore no separate curves for males and female are calculated in the graphic of the combined
analysis. In that case, the outcome of PROAST could be cross-checked by applying BMDS software to
the pooled data. The combined analysis should provide smaller BMDL/BMDU intervals and such the
BMDL should be larger than when calculating separate BMDLs for each sex. This reflects the higher
precision of the BMDL 05 when combining data and such increasing the power of statistical modeling.
The sensitivity of the combined BMD analysis of the data of the two sexes of rats was investigated by
fitting the male and the female data also separately. For the most relevant BMD analysis (epithelial
adenoma or carcinoma in the small intestine in males and females combined) the sensitivity of the
BMDL 10 value on the the number of animals planned and realized in the experiment was investigated,
too (details not reported).
J1. Chromium (VI) neoplastic lesions
J1.1.
BMD analysis of squamous cell neoplastic lesions in male and female rats
The CONTAM Panel identified one data set reported by NTP (NTP 2007, 2008), Stout et al. (2009),
and Witt et al. (2013) on the carcinogenicity of SDD in male and female rats as suitable for DR
assessment of Cr(VI). This Section informs on the details of the analysis at first for male and females
separately using BMDS software and then on result of the analysis when combining males and females.
We start with the evaluation of the carcinoma and papilloma data combined and report then also the
evaluations of the carcinoma data only following the order of the results reported in Table 20 in
Section 7.5.1.
When using the BMDS software, each table informs on the modelling outcome of the non-restricted
models applied to the respective data set following the guidance of EFSA (2009c). The corresponding
figure shows the fit of the model selected (corresponding to the minimum BMDL 10 ). In some cases also
figures of other similarly good fitting models are shown for illustrative reasons. In green are the doseresponse
data with two sided 95 % confidence intervals of the incidences, in red is the fitted curve and
in blue the one-sided 95 % confidence curve from which the BMDL 10 value of the respective model
was derived.
EFSA Journal 2014;12(3):3595 226