Risk assessment of combined exposure to alkenylbenzenes through consumption of plant food supplements containing parsley and dill

Abstract

A risk assessment was performed of parsley- and dill-based plant food supplements (PFS) containing apiol and related alkenylbenzenes. First, the levels of the alkenylbenzenes in the PFS and the resulting estimated daily intake (EDI) resulting from use of the PFS were quantified. Since most PFS appeared to contain more than one alkenylbenzene, a combined risk assessment was performed based on equal potency or using a so-called toxic equivalency (TEQ) approach based on toxic equivalency factors (TEFs) for the different alkenylbenzenes. The EDIs resulting from daily PFS consumption amount to 0.74-125 µg kg bw for the individual alkenylbenzenes, 0.74-160 µg kg bw for the sum of the alkenylbenzenes, and 0.47-64 µg kg bw for the sum of alkenylbenzenes when expressed in safrole equivalents. The margins of exposure (MOEs) obtained were generally below 10,000, indicating a priority for risk management if the PFS were to be consumed on a daily basis. Considering short-term use of the PFS, MOEs would increase above 10,000, indicating low priority for risk management. It is concluded that alkenylbenzene intake through consumption of parsley- and dill-based PFS is only of concern when these PFS are used for long periods of time.

Use of physiologically based kinetic modelling facilitated read-across in risk assessment of botanical food-borne alkenylbenzenes

“…The first one was the slope of the doseresponse curve for DNA-adduct formation in female CD-1 mice liver upon exposure to different alkenylbenzenes . The second one, was the in vivo level of formation of the hepatocarcinogenic 1'-sulfoxymetabolite of the different alkenylbenzenes predicted using human physiologically based kinetic (PBK) models at a dose level of 0.01mg kg -1 bw Al-Malahmeh et al, 2017). A third value was defined based on the BMDL10 values derived from in vivo tumor data for safrole, estragole and methyleugenol , and by read-across from safrole for myristicin and apiol Al-Malahmeh et al, 2017), or by read-across from methyleugenol and estragole for elemicin .…”

“…The second one, was the in vivo level of formation of the hepatocarcinogenic 1'-sulfoxymetabolite of the different alkenylbenzenes predicted using human physiologically based kinetic (PBK) models at a dose level of 0.01mg kg -1 bw Al-Malahmeh et al, 2017). A third value was defined based on the BMDL10 values derived from in vivo tumor data for safrole, estragole and methyleugenol , and by read-across from safrole for myristicin and apiol Al-Malahmeh et al, 2017), or by read-across from methyleugenol and estragole for elemicin . The TEF values for the different alkenylbenzenes defined by the three approaches relative to safrole were subsequently averaged to define the final TEF values .…”

“…Using these TEF values the EDI of alkenylbenzenes in the pesto sauces expressed in (μg methyleugenol equivalents/kg bw per day) was calculated using the formula: , i; differnt alkenybenzenes Table 2. Data used for estimation of the TEF values for the different alkenylbenzenes as derived from data reported for i) the dose-dependent level of DNA adduct formation in the liver of alkenylbenzene exposed female CD-1 mice ii) the formation of the proximate carcinogenic 1'-sulfoxy metabolites in liver in μmol/kg bw as predicted by available PBK models at a dose level of 0.01 mg/kg bw Al-Malahmeh et al 2017), and iii) BMDL10 values reported in the literature Al-Malahmeh et al 2017). The TEF values were calculated relative to methyleugenol as the reference compound, expressing the concentrations of the other alkenylbenzenes in methyleugenol equivalents.…”

“…For this TEQ approach the required toxic equivalency factor (TEF) relative to methyleugenol were estimated as summarized in Table 2. TEF values for the different alkenylbenzenes were defined by calculating the average of the relative potency as available for three end points, including (i) the slope of the dose-response curve for DNA-adduct formation in female CD-1 mice liver upon exposure to different alkenylbenzenes , (ii) the in vivo level of formation of the hepatocarcinogenic 1'-sulfoxymetabolites of the different alkenylbenzenes predicted using human physiologically based kinetic models at a dose level of 0.01 mg/kg bw Al-Malahmeh et al 2017), and (iii) the BMDL10 values derived from in vivo tumor data for safrole, estragole, and methyleugenol , or by read-across from safrole for myristicin and apiol Al-Malahmeh et al 2017).…”

“…Risk assessment of consumption of the nutmeg-based PFS samples was performed using the MOE approach . For the individual alkenylbenzene approach, the BMDL10 values of the individual compounds were used Al-Malahmeh et al, 2017), and then compared with the EDIs of the alkenylbenzenes resulting from the use of nutmeg-based PFS. For the equal potency assumption approach, the BMDL10 value of myristicin, the major alkenylbenzene in most of the samples, was used and compared to the sum of the EDIs.…”