Combined Actions and Interactions of Chemicals in Mixtures

On the basis of a common receptor-mediated mechanism of toxic action, the
relative immunotoxicity of individual PCDDs and PCDFs can be expressed relative
to TCDD (Vos et al. 1997). When the immunotoxicity of a mixture of PCDDs and
PCDFs are calculated and additive effect is assumed because of the common
receptor mediated toxicity.
7.7.1.5 Conclusion
The many different cell types involved in the function of the immune system gives
many theoretical possibilities of combined immunotoxic effects. As apparent from
the above there are yet few experimental data to draw upon. Chemicals sharing a
common toxic mechanism seem to have an additive effect. Competition for
metabolising enzymes may antagonise the immunotoxic effect. How mixtures of
chemicals that are toxic to different branches of the immune system will exert their
combined immunotoxic effect remains to be established.
7.7.2 Allergy
7.7.2.1 Introduction
In the following the possible consequence of combined exposure to different
chemical allergens on the skin will be discussed. Respiratory allergy to small
molecular weight chemicals will not be covered because of lack of data.
7.7.2.2 Allergic contact dermatitis
Skin contact with chemical compounds may induce cellular mediated contact
sensitisation. The consequence of this contact sensitisation can be allergic contact
dermatitis.
Most contact allergens are small molecules with a molecular weight below 600
dalton. Contact sensitisation is not inborn but is always a consequence of earlier
cutaneous contact. Contact sensitisation is considered to be life-long, but may
become weaker if exposure is avoided. Contact sensitised individuals are at risk of
developing the skin disease allergic contact dermatitis if re-exposed to the specific
chemical (IPCS 1999).
7.7.2.3 Patch test
Contact sensitisation to environmental chemicals is diagnosed by the use of patch
testing. The test is a biological test where contact allergy is proven by re-exposing
the skin to the specific chemical under occlusion on a 0.5 cm 2 large skin area on
the upper back for 2 days. A positive test is a reproduction of the clinical disease
showing redness, infiltration and eventual vesicles. All patients are primarily tested
with the Standard series including the most frequent sensitising chemicals such as
metals, preservatives, fragrances, rubber additives, and topically used
medicaments. Sensitisation can be quantified according to the degree of positive
patch test reaction (+ to +++), patch test concentration threshold defined by
dilution series, and finally by the “Use test”. In the latter test the individual is
exposed to the chemical simulating normal use (IPCS 1999).
7.7.3 Patch test results with mixtures of chemicals
It is common clinical experience that testing with a mixture of substances, for
instance a cosmetic product may cause a positive patch test reaction and
subsequent testing of the single ingredients a negative response (Johansen et al
1998). In accordance with this Johansen and Menné (1995) found that only half of
the patients reacting to fragrance mix from the European Standard patch test series
also gave a positive response to at least one of the eight fragrance mix constituents
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