Neurotoxicity chemical mixtures

Many household products contain neurotoxic chemical mixtures. These include fragrance products [111], marking pens [112], and air fresheners [113]. These products contain mixtures of lipophilic and hydrophilic chemicals and exposures in home use are typically far below the TLVs of any of the individual chemicals. Exposures to these products, however, in test chambers produce unpredicted behavioral abnormalities in laboratory animals including altered gait, loss of balance, hypoactivity, tremors, and other symptoms. Though no specific human neurotoxic effects have been noted, these studies suggest that neurotoxic impacts on people are likely. 

Exposure to a single PAH compound seldom occurs in situations of relevance to local law enforcement agencies or defense forces. Often, people are exposed to PAHs in combination with other toxicants such as aliphatic hydrocarbons and/or metals (NRC, 2005). Information on toxicity of chemical mixtures, of which PAHs are a constituent, is lacking. Until such studies are undertaken in animal models, it is difficult to establish whether PAHs have an additive or a synergistic effect in determining neurotoxicity. 

In keeping with the purpose of this book, the discussion of the neurotoxic effects of single chemicals will serve only as an introduction to the discussion of the neurotoxic effects of chemical mixtures. 

Numerous neurotoxic chemicals have been identified. These include pesticides (particularly, but not limited to, organophosphates and carbamates), aliphatic and aromatic hydrocarbons, alcohols, ethers, ketones, heavy metals (including lead, mercury, manganese, and others), and mixtures of these. Hundreds of individual chemicals are established or suspected neurotoxins. The EPA Guidelines for Neurotoxicity Risk Assessment and the Scorecard list of neurotoxicantsl5 contain partial lists of neurotoxic chemicals. The actual number of chemicals with neurotoxic potential has been estimated to range between 3% and 28% of all the approximately 80,000 chemicals in use (2400-22,400) Clearly, the number of mixtures possible is infinite, though little attention has been devoted to the neurotoxic effects of mixtures. 

The mechanisms by which many neurotoxic chemicals and chemical mixtures act remain unknown. Much of the knowledge regarding the... 

The case studies presented here are all from the published literature. In every study the neurotoxic effects found are related to exposures to chemical mixtures of lipophiles and hydrophiles that induced neurotoxic effects not anticipated from the individual chemicals. The Kovi/ values for each of the chemicals are given. If not listed in a column they follow the individual chemical names in parentheses. 

Multiple neurotoxic effects can be induced by exposures to mixtures of lipophilic and hydrophilic chemicals at levels below those known to be neurotoxic for the individual chemicals. It is hypothesized that lipophilic chemicals facilitate the absorption of hydrophilic species resulting in the uptake of greater quantities of hydrophiles than would occur in the absence of the lipophiles. Neuropathies, behavioral changes, and neurodegenera-tive diseases have been shown to be caused by these mixtures, often via unknown mechanisms. Both acute and chronic low level effects following exposures to such mixtures have been reported. Since exposures to chemicals almost always are to mixtures, the need to lower the threshold limit values for neurotoxic chemicals is indicated. 

Other studies that have addressed the developmental neurotoxicities of chemical mixtures include the following ... 

Perinatal exposure of mice to dieldrin alters the dopaminergic neurochemistry in their offspring. Exposure to a mixture of dieldrin and MPTP during development exacerbates the neurotoxicity of MPTP, a known chemical cause of Parkinson s disease. This study serves as a model for the induction of Parkinson s disease by chemical mixtures. I26l... 

Very few studies have been carried out on the developmental neurotoxicity of chemical mixtures. Those that have been reported, however, have demonstrated enhanced or unanticipated neurotoxic effects following mixture exposures. 

Mixtures of chemicals have been shown to produce neurotoxic effects that are not predicted from the known toxicology of the mixtures individual chemicals. Low concentrations of chemical mixtures produce unusual and unexpected CNS effects.I37-40 These effects are confounded by concurrent exposure to other toxic chemicalsJ41 ... 

It is estimated that 28% of all chemicals used in commerce could be neurotoxicJ42l Common household products including air fresheners, fragrance products, marking pens, and mattress covers contain known neurotoxins. I43 461 The neurotoxic effects of marking pens are attributed to chemical mixtures. I46l Aspertaine, saccharin, artificial food colors, benzyl alcohol, and other excipients used in pharmaceutical preparations and foods are neurotoxins. I47 48 ... 

Virtually aU human environmental exposures to toxic chemicals are to mixtures. This is particularly the case for exposures to pesticides, heavy metals, and organic solvents, known as neurotoxins. Despite this, relatively few studies have been carried out on the neurotoxic effects of chemical mixtures. This section addresses the results of these mixture studies. 

The developing fetus and the growing child are at greater risk than adults are from exposur es to neurotoxic chemicals. Relatively little is known about developmental neurotoxic effects of single chemicals and even less about the effects of chanical mixtures. 

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