Combined Actions and Interactions of Chemicals in Mixtures

substances and 15 allergic to only one of the same two fragrances. The test and
matched control subjects were patch tested with two allergens applied in serial
dilutions in separate chambers on one side and combined in one chamber on the
other side of the upper back. The assessment of reaction was carried out on day 3
by clinical grading and by measuring the blood flow using laser Doppler
flowmetry. The extent of the reaction was measured in millimetres. The 1:1
mixture of the two allergens elicited responses as if the doses were three to four
times higher than those actually used. This result was obtained both for the clinical
grading, the blood flow and the size of reaction in mm. The data were analysed by
logistic dose-response models comparing the horizontal displacement of the doseresponse
curves. The conclusion of the study is that the combination of two
allergens had a synergistic effect on the elicitation response (Johansen et al 1998).
In all three studies elicitation of an allergic response is enhanced if two unrelated
allergens are mixed. It is possible to elicit a response by using a subthreshold dose
for both allergens and it is possible to enhance the response at levels above the
threshold dose. McLelland and Shuster conclude that the effect is additive and
Johansen that it is synergistic. Johansen uses a statistical method that is used in
pharmacology and toxicology to assess relative potency and possible interaction
between two drugs. McLelland and Shuster add the results from the linear part of
the dose-response curve only. Even though they show that there is synergy below
the threshold level they do not include this in the conclusion. The data presented by
Johansen and by McLelland and Shuster are very similar. The discrepancy in
conclusions stems from the different use of statistics.
7.7.5 Sensitisation
Inhibition of sensitisation, also called quenching, has been described .for chemicals
in essential oils thought to be able to inhibit sensitisation to contact allergens in the
same oil. The phenomenon has been studied extensively by Basketter and Allenby
(1991). However, these investigators were not able to confirm the existence of
inhibition of sensitisation of one chemical by the simultaneous application of
another.
In a study of the influence of the skin irritant sodium lauryl sulphate (SLS) on
sensitisation to 2,4,-dinitrochlorobenzene Cumberbatch et al (1993) found that SLS
did not enhance sensitisation by increased skin penetration but by an increase in the
number of immunostimulatory dendritic cells from the skin which reach the
draining lymph node. van’t Erve et al (1998) found that the cellular and humoral
response to the contact allergen oxazolone was dissimilary affected by the vehicles
used. A wet work environment will also enhance the possibility of sensitisation as
water helps to break down the skin barrier. Occlusion e.g. gloves, armpits, will also
facilitate sensitisation. Skin disease will do the same. The increased sensitisation
may be induced by increased penetration of the skin, or other mechanisms as in the
SLS study.
7.7.6 Conclusion
If a person allergic to two unrelated allergens is challenged with these two
allergens in combination the subsequent elicitation response will be the sum or
greater than the expected sum of response to the two allergens alone. The challenge
with two allergens combined at subthreshold doses can elicit a response that none
of the allergens alone at that dose may elicit.
The consequence of this is that a person may be negative in a diagnostic patch test
with single chemicals although a mixture of chemicals would produce a reaction.
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