Combined Actions and Interactions of Chemicals in Mixtures

In case of substances with different toxic effects and mode of action the C-values
for each substance should be complied with separately.
In case of substances that affect each other’s effect and mode of action the Cvalues
for each substance should be complied with separately, as well, as no
interaction is expected to occur at concentrations below the C-values, which
represent human no-effects levels of the specific compounds. The assumption is
that interaction only occurs at levels above the no-effect levels.
In case of substances with identical effects and mode of action and in case of
substances from the same chemical homologous group (e.g. alcohols, ketones,
ethers, etc) the contribution from each substance (in relation to their respective Cvalue)
should be added together, i.e. simple additivity of the effect is assumed.
In relation to PAH-emissions, the emission value is based on a specific
benzo[a]pyrene equivalent value based on the contribution and relative potency
factors of 15 PAH-substances.
4.6.3 The Danish Veterinary and Food Administration
The Danish Veterinary and Food Administration follows the international
evaluations of chemicals in food, which in a number of cases consider the
possibility of combined actions of chemicals. One of the most well known
examples is the use of toxicity equivalency factors for the evaluation of mixtures of
polychlorinated dibenzo-p-dioxins, dibenzofurans and biphenyls in food.
For a number of food additives, group ADIs have been established. Examples are
groups of food preservatives like sorbic acid and sorbates, benzoic acid and
benzoates and the parabenes (ethyl-, methyl- and propyl-para-hydroxybenzoates).
They have all been allocated group ADIs, which means that the intake of the sum
of the amounts of each compounds in the group (obtained through simple addition)
should not exceed the group ADI. For benzoic acid and the benzoates, the group
ADI of 0-5 mg/kg bw/day also includes the intake of the flavouring agents benzyl
acetate and other benzyl esters, benzyl alcohol and benzaldehyde. The rationale
behind this is that these compounds are all quickly and efficiently metabolised into
benzoic acid.
4.6.3.1 Risk assessment of pesticide residues in food
Prepared by Trine Klein Reffstrup
The current practice in risk assessment of multiple pesticide residues in food is
generally based upon data from studies on single compounds although humans at
the same time are exposed to more than one pesticide that potentially possesses
similar or different toxic effects. Thus, Chambers and Dorough (1994) discussed
the fact that almost all pesticides occur in mixtures. “Pesticides are applied to
crops, forests, home gardens, households and buildings as formulated products that
contain solvents, emulsifiers, and “inert” ingredients. Moreover, technical grades
of pesticide compounds contain isomers, analogues, breakdown products, or
rearrangement products that form during synthesis and are not removed or that
form after synthesis and/or formulation and during storage.”
These compounds may interact causing a higher or lower toxic effect than would
be expected from the single compounds. Consequently potential combined actions
of pesticides need to be addressed in the risk assessment process. However, there is
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