Sa. Carpy et al., Health risk of low-dose pesticides mixtures: A review of the 1985-1998 literature on combination toxicology and health risk assessment, J TOX E H B, 3(1), 2000, pp. 1-25
Citations number
67
Categorie Soggetti
Environment/Ecology,"Pharmacology & Toxicology
Journal title
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART B-CRITICAL REVIEWS
A literature review covering the last 14 yr has been performed in the field
of combination toxicology and human risk assessment from exposure to chemi
cal mixtures, with special emphasis on mixtures of pesticides at low doses,
that is, at levels likely to occur in human diet and environment. Despite
a large body of knowledge in the field of risk assessment methodologies for
exposure to chemical and pesticide mixtures, there is no single methodolog
ical approach in "combination toxicology" and health risk assessment of che
mical mixtures, and therefore professional judgment is still required Gener
ally, the dose or response additivity approach that may be applied to evalu
ate potential risk for chemical mixtures in human toxicology overestimates
the risk of a combination of chemicals. The recent endocrine disrupter issu
e demonstrated the difficulty of reproducibility of data when testing envir
onmental toxicants at very low levels, and the need for more basic work in
this; field The use of integrated methodological approaches may provide mor
e reliable predictive data in the risk assessment of chemical mixtures in f
uture. Yet data have demonstrated that exposure to a combination of compoun
ds does not cause effects stronger than the ones of their most active compo
nent, provided components are present at low concentration levels, like acc
eptable daily intake (ADI) or reference dose (RfD) levels, well below their
respective no-observed-adverse-effect levels (NOAELs), Although it has bee
n demonstrated that a combination of compounds with the same target organ a
nd the same or very similar mechanisms of action may cause additive or syne
rgistic effects, the chance of such effects will most likely diminish with
decreasing exposure levels to such combinations. Synergism and antagonism m
ay both occur at the same time at different organs or targets in the same o
rganism. However, and despite some exceptions, it has been demonstrated tha
t interaction between components is not a common event at low levels of hum
an exposure such as those that may occur through pesticides residues in foo
d or drinking water. The introduction of a special safety factor as a stand
ard for mixtures in addition to those normally used for deriving ADIs, RfDs
, or minimal risk levels is not supported by data. it can be concluded from
our review that, as a general rule, exposure to mixtures of pesticides at
low doses of the individual constituents does not represent a potential sou
rce of concern to human health.