HEALTH RISKS FROM COMBINED EXPOSURES - MECHANISTIC CONSIDERATIONS ON DEVIATIONS FROM ADDITIVITY

BURKART W JUNG T

W. Burkart et T. Jung, HEALTH RISKS FROM COMBINED EXPOSURES - MECHANISTIC CONSIDERATIONS ON DEVIATIONS FROM ADDITIVITY, Mutation research. Reviews in mutation research, 411(2), 1998, pp. 119-128

25

INGLESE

Review

Genetics & Heredity",Toxicology,"Biothechnology & Applied Migrobiology

Mutation research. Reviews in mutation research → ACNP

1383-5742

411

2

1998

119 - 128

ISI

1383-5742(1998)411:2<119:HRFCE->2.0.ZU;2-R

Living organisms are exposed every day to a multitude of physical, che mical and biological agents. However, assessments of possible deleteri ous outcomes from these exposures concentrate on single agents and neg lect the potential for combined effects, i.e., synergisms or antagonis ms. Biomechanistic considerations based on multistep processes such as carcinogenesis indicate the potential for highly detrimental interact ions, if two or more consecutive rate limiting steps are specifically effected by different agents. However, this depends on the specificity of the individual agents for well defined molecular structures or DNA sequences. Low specificity towards molecular structure or DNA-sequenc e-and therefore exchangeability-of many genotoxic agents indicate litt le functional specificity of most agents and therefore little vulnerab ility towards synergism at most occupational and non-occupational expo sure situations. In addition, the relative insignificance of combined actions for those common exposure situations where highly non-linear d ose effect relationships for non-genotoxic acting agents are involved is also evident. However, an experimental proof of the quantitative as sessment of the contribution of synergistic interactions to the total detriment from natural and man-made toxicants is remote. Surprises the refore cannot be excluded. (C) 1998 Elsevier Science B.V. All rights r eserved.