Combinations of Endocrine Disruptors

Endocrine disruptors are a diverse group of chemicals with the ability to interfere with the normal action of hormones. A diversity of mechanisms is at play, ranging from mimickry of endogenous hormones to disruption of normal hormone action by antagonism of receptor binding or interference with hormone metabolism. In the last 10 years, good evidence (reviewed by Kortenkamp 2007) has become available to show that the combined effects of endocrine disruptors belonging to the same category (e.g.,...

MixTuRE EFFEcTs AT LoW LEvELs

A key issue that drives chemical risk assessment as well as evaluations of the health impacts of existing pollution is whether chemicals produce combination effects when they are present at levels that individually do not induce observable effects. It is often Figure 3.4 Illustration of a sham mixture experiment with chemicals that all exhibit the same dose-response curve. At the low dose to the left (arrow, 4 x 10-3 M), the effect is hardly observable. A combination of ten agents, at this dose...

WHAT ABouT The Real World

Mixture toxicology, although an interesting issue, is only of theoretical relevance when the levels of chemicals that occur together in the real world are too low to be of concern. Therefore, what is the evidence that large numbers of chemicals occur together, and are there indications that chemicals might have a combined effect Because pesticides are inherently toxic and are deliberately released into the environment, their distribution and fate are comparatively well monitored. Multiple...

Toxicodynamic studies of chemical Mixtures using physiologically or Biologically Based modeling

Because physiologically based toxicodynamic (PBTD) modeling of chemical mixtures is still at its infancy, we choose to only briefly discuss PBTD modeling by concentrating on a number of published and 1 unpublished example on binary mixtures. For more details on the basic principles of PBTD modeling and specific information on the several case studies discussed below, the reader is encouraged to consult the original references. 2.4.3.1.1 Toxicodynamic Modeling of Noncancer Effects of Chemical...

Table 21 The parameters most frequently used in human and mammalian pBTK models

Physiological physicochemical Biochemical Cardiac output Partition coefficients Rate constants (Vmax, Km) for Body weight Tissue-blood Metabolism Tissue volumes Blood-air Urinary excretion Tissue blood flow Blood-water (fish) Biliary excretion Glomerular filtration rate Skin-air Macromolecular binding constants Tissue blood content Skin-water Bmax Tissue lipid and water content Permeability coefficients Kd partition coefficients can be estimated using in vitro approaches such as...

Chemical Chemical Interactions in Mixtures

Another form of interaction that may change the nature of exposure for chemicals in mixtures is through direct chemical-chemical interaction. One example is the formation of nitrosamines (which are carcinogenic) from noncarcinogenic nitrates and amines in the stomach (Klaassen 1996). The formation of N-nitrosoatrazine from atrazine and nitrite has been demonstrated in vitro in human gastric juice (pH 1.5 to 2.0) during 1.5 to 12 hours of incubation at 37 C (Cova et al. 1996). The percent...

Toxicokinetics and toxicodynamics

After uptake, a chemical may be absorbed, distributed, metabolized, and excreted (toxicokinetics (TK)), and once the biological target in the organism has been reached it may exert toxic effects (toxicodynamics (TD)). So, toxicokinetics can be considered what the body does with the chemicals, and toxicodynamics what the chemicals do to the body. TK modeling within human toxicology is well established, and there are good data and models at the level of binary mixtures. The binary to...

Glossary

Acute Occurring within a short period in relation to the life span of the organism usually 4 days for fish . It can be used to define either the exposure acute test or the response to an exposure acute effect . Acute toxicity The harmful effects of a chemical or mixture of chemicals occurring after a brief exposure to relatively high concentrations. See also chronic toxicity. ADI Acceptable daily intake. The amount of a substance that could be consumed daily for an entire life span without...