Determination and risk assessment of naturally occurring genotoxic and carcinogenic alkenylbenzenes in basil-containing sauce of pesto.

A risk assessment of basil-based pesto sauces containing methyleugenol and related alkenylbenzenes was performed based on their levels detected in a series of pesto sauces available on the Dutch market. The estimated daily intake (EDI) values of alkenylbenzenes as a result of consumption of the different pesto sauces amounted to 1.2-44.3 µg/kg bw for individual alkenylbenzenes, 14.3-43.5 µg/kg bw when adding up the alkenylbenzene levels assuming equal potency, and 17.3-62.9 µg/kg bw when expressed in methyleugenol equivalents using alkenylbenzenes defined toxic equivalency factors (TEF). The margin of exposure approach (MOE), used to evaluate the potential risks, resulted in MOE values that were generally lower than 10000 indicating a priority for risk management when assuming daily consumption. The levels of methyleugenol detected in the pesto sauces would allow consumption of 1.1-29.8, 7.5-208, 15.1-416.5, and 32.4-892.5 g of pesto sauce on a daily basis, once a week, once every two weeks, and once a month, respectively, to achieve MOE values above the 10000 limit indicating low priority for risk management. It is concluded that consumption of pesto sauces would only be of concern if consumed on a daily basis over longer periods of time.

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

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-1 bw for the individual alkenylbenzenes, 0.74-160 µg kg-1 bw for the sum of the alkenylbenzenes, and 0.47-64 µg kg-1 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.

Determination and risk assessment of naturally occurring genotoxic and carcinogenic alkenylbenzenes in nutmeg-based plant food supplements.

A risk assessment of nutmeg-based plant food supplements (PFS) containing different alkenylbenzenes was performed based on the alkenylbenzene levels quantified in a series of PFS collected via the online market. The estimated daily intake (EDI) of the alkenylbenzenes amounted to 0.3 to 312 µg kg-1 body weight (bw) for individual alkenylbenzenes, to 1.5 to 631 µg kg-1 bw when adding up the alkenylbenzene levels assuming equal potency, and to 0.4 to 295 µg kg-1 bw when expressed in safrole equivalents using toxic equivalency factors (TEFs). The margin of exposure approach (MOE) was used to evaluate the potential risks. Independent of the method used for the intake estimate, the MOE values obtained were generally lower than 10000 indicating a priority for risk management. When taking into account that PFS may be used for shorter periods of time and using Haber's rule to correct for shorter than lifetime exposure it was shown that limiting exposure to only 1 or 2 weeks would result in MOE values that would be, with the presently determined levels of alkenylbenzenes and proposed uses of the PFS, of low priority for risk management (MOE > 10000). It is concluded that the results of the present paper reveal that nutmeg-based PFS consumption following recommendations for daily intake especially for longer periods of time raise a concern. Copyright © 2017 John Wiley & Sons, Ltd.

Physiologically based kinetic modeling of the bioactivation of myristicin.

The present study describes physiologically based kinetic (PBK) models for the alkenylbenzene myristicin that were developed by extension of the PBK models for the structurally related alkenylbenzene safrole in rat and human. The newly developed myristicin models revealed that the formation of the proximate carcinogenic metabolite 1'-hydroxymyristicin in liver is at most 1.8 fold higher in rat than in human and limited for the ultimate carcinogenic metabolite 1'-sulfoxymyristicin to (2.8-4.0)-fold higher in human. In addition, a comparison was made between the relative importance of bioactivation for myristicin and safrole. Model predictions indicate that for these related compounds, the formation of the 1'-sulfoxy metabolites in rat and human liver is comparable with a difference of <2.2-fold over a wide dose range. The results from this PBK analysis support that risk assessment of myristicin may be based on the BMDL10 derived for safrole of 1.9-5.1 mg/kg bw per day. Using an estimated daily intake of myristicin of 0.0019 mg/kg bw per day resulting from the use of herbs and spices, this results in MOE values for myristicin that amount to 1000-2700, indicating a priority for risk management. The results obtained illustrate that PBK modeling provides insight into possible species differences in the metabolic activation of myristicin. Moreover, they provide an example of how PBK modeling can facilitate a read-across in risk assessment from a compound for which in vivo toxicity studies are available to a related compound for which tumor data are not reported, thus contributing to alternatives in animal testing.

Level of Alkenylbenzenes in Parsley and Dill Based Teas and Associated Risk Assessment Using the Margin of Exposure Approach.

Risk assessment of parsley and dill based teas that contain alkenylbenzenes was performed. To this end the estimated daily intake (EDI) of alkenylbenzenes resulting from use of the teas was quantified. Since most teas appeared to contain more than one alkenylbenzene, a combined risk assessment was performed based on equal potency of all alkenylbenzenes or using a so-called toxic equivalency (TEQ) approach through defining toxic equivalency factors (TEFs) for the different alkenylbenzenes. The EDI values resulting from consuming one cup of tea a day were 0.2-10.1 µg/kg bw for the individual alkenylbenzenes, 0.6-13.1 µg/kg bw for the sum of the alkenylbenzenes, and 0.3-10.7 µg safrole equiv/kg bw for the sum of alkenylbenzenes when expressed in safrole equivalents. The margin of exposure (MOE) values obtained were generally <10000, indicating a concern if the teas would be consumed on a daily basis over longer periods of time.

Mode of action based risk assessment of the botanical food-borne alkenylbenzene apiol from parsley using physiologically based kinetic (PBK) modelling and read-across from safrole.

The present study developed physiologically-based kinetic (PBK) models for the alkenylbenzene apiol in order to facilitate risk assessment based on read-across from the related alkenylbenzene safrole. Model predictions indicate that in rat liver the formation of the 1'-sulfoxy metabolite is about 3 times lower for apiol than for safrole. These data support that the lower confidence limit of the benchmark dose resulting in a 10% extra cancer incidence (BMDL10) that would be obtained in a rodent carcinogenicity study with apiol may be 3-fold higher for apiol than for safrole. These results enable a preliminary risk assessment for apiol, for which tumor data are not available, using a BMDL10 value of 3 times the BMDL10 for safrole. Based on an estimated BMDL10 for apiol of 5.7-15.3 mg/kg body wt per day and an estimated daily intake of 4 × 10(-5) mg/kg body wt per day, the margin of exposure (MOE) would amount to 140,000-385,000. This indicates a low priority for risk management. The present study shows how PBK modelling can contribute to the development of alternatives for animal testing, facilitating read-across from compounds for which in vivo toxicity studies on tumor formation are available to compounds for which these data are unavailable.

(226)Ra measurement by LSC as a tool to assess the efficiency of a water treatment technology for removing radionuclides from groundwater.

A simple (226)Ra analysis procedure by LSC with an extractive scintillator was tested for evaluating the long-term radionuclides removal efficiency of a water treatment facility at Viimsi, Estonia. During the 14 months of operation, total radium removal efficiency of the treatment process has stayed over 90%, but the removal efficiencies of the different purification steps have varied notably. This demonstrates the need for routine monitoring of radium content in the water treatment plant.