Retrospective cumulative dietary risk assessment of craniofacial alterations by residues of pesticides

Abstract

EFSA established cumulative assessment groups and conducted retrospective cumulative risk assessments for two types of craniofacial alterations (alterations due to abnormal skeletal development, head soft tissue alterations and brain neural tube defects) for 14 European populations of women in childbearing age. Cumulative acute exposure calculations were performed by probabilistic modelling using monitoring data collected by Member States in 2017, 2018 and 2019. A rigorous uncertainty analysis was performed using expert knowledge elicitation. Considering all sources of uncertainty, their dependencies and differences between populations, it was concluded with varying degrees of certainty that the MOET resulting from cumulative exposure is above 100 for the two types of craniofacial alterations. The threshold for regulatory consideration established by risk managers is therefore not exceeded. Considering the severity of the effects under consideration, it was also assessed whether the MOET is above 500. This was the case with varying levels of certainty for the head soft tissue alterations and brain neural tube defects. However, for the alterations due to abnormal skeletal development, it was found about as likely as not that the MOET is above 500 in most populations. For two populations, it was even found more likely that the MOET is below 500. These results were discussed in the light of the conservatism of the methodological approach.

Keywords: craniofacial alterations; cumulative assessment groups; cumulative risk assessment; expert knowledge elicitation; pesticide residues; probabilistic modelling; uncertainty analysis.

Figure 1

General process for calculating acute cumulative exposure to pesticides

Figure 2

Overview of the approach to characterising overall uncertainty in the CRA

Figure 3

Scale used by the experts when assessing EKE Q1

Figure 4

Schematic representation of the RA‐related pathway involved in craniofacial development (Menegola et al., 2021)

Figure 5

CAG‐DAC: Consensus distribution of the experts for the combined impact of the quantified uncertainties affecting toxicology (if resolved) on the MOET at the 99.9th percentile of exposure for the German population, expressed as a multiplicative factor f to be applied to the Tier II median estimate shown in Table 16. The probability distribution is shown by the curve, which represents the probability density (relative likelihood) for different values of the multiplicative factor f. Distribution parameters are shown in Table 24.

Figure 6

CAG‐DAH: consensus distribution of values of the multiplicative factor representing the combined effect of toxicology uncertainties

Figure 7

CAG‐DAC: consensus distribution of values of the multiplicative factor representing the combined effect of exposure uncertainties

Figure 8

CAG‐DAH: consensus distribution of values of the multiplicative factor representing the combined effect of exposure uncertainties

Figure 9

CAG‐DAC: Combination of MOET estimates and confidence intervals at the 99.9th percentile of exposure in each consumer population, with the elicited distributions of multiplicative factors quantifying the impact of uncertainties related to toxicology and exposure

1. Keys: ‘Model’ boxplots show the output of the Tier II model for the MOET at the 99.9th percentile of exposure in each consumer population. ‘Model+experts’ boxplots show the result of combining the output of the Tier II model with the distributions of multiplicative factors quantifying additional sources of uncertainty related to toxicology and exposure, as elicited for the German population, assuming perfect independence between them. Note that the vertical axis is plotted on a logarithmic scale; the values plotted for ‘model+experts’ are shown numerically in Table 28. The lower and upper edges of each boxplot represent the quartiles (P25 and P75) of the uncertainty distribution for each estimate, the horizontal line in the middle of the box represents the median (P50) and the ‘whiskers’ above and below the box show the 95% probability interval (P2.5 and P97.5).

Figure 10

CAG‐DAH: Combination of MOET estimates and confidence intervals at the 99.9th percentile of exposure in each consumer population, with the elicited distributions of multiplicative factors quantifying the impact of uncertainties related to toxicology and exposure. Graph content is explained in Figure 9

Figure F.1

Distributions quantifying uncertainty of the MOET for the 99.9th percentile exposure based on Tier II output for CAG‐DAC, with folpet included, folpet excluded, and folpet included in the CAG with higher probability (70%) or lower probability (40%) bounds

Figure F.2

Violin plots for the confidence intervals of the MOET at the 99.9th percentile of the exposure distributions for the Tier II scenario of CAG‐DAC in women of childbearing age, presented by country

1. Legend: The width of violin is proportional to density of observation for each value of the MOET at the 99.9th percentile of the exposure distribution. The 95% confidence interval is delimited by the black vertical lines, whereas the quartiles are highlighted in green. Mean and median values are indicated by a red and a blue line, respectively. The confidence intervals are plotted on a logarithmic axis.

Figure F.3

Violin plots for the confidence intervals of the MOET at the 99.9th percentile of the exposure distributions for the Tier II scenario of CAG‐DAH in women of childbearing age, presented by country

1. Legend: The width of violin is proportional to density of observation for each value of the MOET at the 99.9th percentile of the exposure distribution. The 95% confidence interval is delimited by the black vertical lines, whereas the quartiles are highlighted in green. Mean and median values are indicated by a red and a blue line, respectively. The confidence intervals are plotted on a logarithmic axis.

Figure F.4

Density plot for a skewed distribution (lognormal)

Figure F.5

Density plot of the observed 99.9th percentile of 1000 simulated samples (each with a sample size of 1000 values)

Figure H.1

CAG‐DAC – Multiplicative factor for toxicology uncertainties: First provisional consensus distribution. Beta with median of 1.33 and 90% probability interval of 0.82–1.86

Figure H.2

CAG‐DAC – Multiplicative factor for toxicology uncertainties: Second provisional consensus distribution. Beta with median of 1.32 and 90% probability interval of 0.86–1.88

Figure H.3

CAG‐DAC – Multiplicative factor for toxicology uncertainties: Consensus distribution. Beta with median of 1.31 and 90% probability interval of 0.86–1.94

Figure H.4

CAG‐DAH – Multiplicative factor for toxicology uncertainties: Provisional and consensus distribution. Scaled‐Beta with median of 1.03 and 90% probability interval of 0.64–1.39

Figure I.1

CAG‐DAC – Multiplicative factor for exposure uncertainties: First provisional consensus distribution. Scaled Beta with median of 1.58 and 90% probability interval of 0.96–2.30

Figure I.2

CAG‐DAC – Multiplicative factor for exposure uncertainties: Consensus distribution. Scaled Beta with median of 1.50 and 90% probability interval of 0.85–2.30

Figure I.3

CAG‐DAC – Multiplicative factor for exposure uncertainties: Alternative distribution. Scaled Beta with median of 1.50 and 90% probability interval of 0.83–2.26

Figure I.4

CAG‐DAH – Multiplicative factor for exposure uncertainties: First provisional consensus distribution. Scaled Beta with median of 1.22 and 90% probability interval of 0.81–1.58

Figure I.5

CAG‐DAH – Multiplicative factor for exposure uncertainties: Consensus distribution. Scaled Beta with median of 1.20 and 90% probability interval of 0.64–1.73