Hydrophiles chemical mixtures

As can be seen from these data, all four THMs are of similar lipophilic-ity. Individually and together they facilitate the absorption of hydrophiles dissolved in them. Drinking water contains hundreds of dissolved chemicals in addition to DBPs. It is believed that the spontaneous abortions observed are because of a lipophilic/hydrophilic chemical mixture of DBPs and/or other dissolved chemicals of unknown compositionJ63 ... 

In 2003, Zeliger reported that in all cases of these unusual effects of mixtures cited in the literature, the mixtures contained at least one lipophilic and one hydrophilic chemical. A lipophilic chemical is one that exhibits preferential solubility in relatively less polar species. A hydrophilic chemical is one that exhibits preferential solubility in relatively more polar species. Lipophiles promote the permeation of hydrophiles through mucous membranes resulting in the absorption of greater quantities of hydrophilic species than would be absorbed if the lipophile were not present. Once absorbed, the mixtures of chemicals may affect the body in ways not anticipated from the actions of single chemicals alone. It was found that the effects of the absorbed mixtures may be acute or chronic. ... 

Traditional toxicology addresses the toxic effects of single chemicals and even some mixtures (additivity, potentiation, and synergism) well, but it is unable to account for some observed effects of chemical mixtures. These unexplained effects often ensue when exposures are to mixtures of lipophilic and hydrophilic chemicals. Octanokwater partition coefficients serve to predict the lipophilic or hydrophilic nature of chemical compounds. 

The majority of xenobiotics that are absorbed by the body are lipophilic and can permeate through body membranes. The uptake of hydrophilic species by the body, however, be they solvents, pharmaceuticals, or other chemicals are facilitated by the presence of lipophilic species. Kow values predict which chemicals are hydrophiles and which are lipophiles. Exposures to chemical mixtures of lipophiles and hydrophiles will result in the absorption of greater quantities of hydrophiles than would be taken up if these species were present alone. 

At times, such as in drug administration, lipophiles are deliberately added to hydrophilic pharmaceuticals to facilitate absorption. Most often, however, the administering of combinations of lipophilic and hydrophilic chemicals is unintentional and leads to enhanced toxic effects on the body. Once taken up by the body, the distribution, metabolism, immune system response, endocrine system response, and effects on a wide variety of organs in the body are impacted by the mixtures and their metabolites. 

Water pollution causes the introduction of a very wide variety of toxic chemicals to those drinking, cooking, and bathing with impure water. There are numerous sources of pollutants that end up in potable water, and the mixtures produced by many of these pollutants result in unexpected toxic effects in people who consume such water. Mixtures of lipophilic and hydrophilic chemicals have been demonstrated to be causative for many of these unanticipated toxic effects. 

Most of the chemicals in Table 11.2 target the respiratory system and CNS. Exposures in arts and crafts use are almost always to mixtures of lipophilic and hydrophilic chemicals. When used in areas with poor air circulation (as is often the case in home use) the result can be unexpected acute toxicity. For example, it has been reported that exposure to formaldehyde and terpene hydrocarbons at very low levels unexpectedly produced dyspnea and other lower-lung symptoms in wood workers. The effects could not be attributed to either the formaldehyde or the terpenes alone at low levels of exposure In another example, it was reported that chronic exposure to a combination of very low concentrations of MEK, ethyl acetate, and aliphatic hydrocarbons in a leather adhesive formulation induced unanticipated CNS effects. Some products that are considered by most... 

Chemical mixtures in cosmetics give rise to enhanced toxicity, low level toxicity, and unexpected target organ attack. Cosmetic products are composed of many lipophilic and hydrophilic chemicals. Numerous instances of strange injuries, including chemical burns and skin and respiratory sensitization from the use of cosmetic products, have been documented in which the injuries sustained could not be accounted for by a consideration of the individual chemicals involved J3°l... 

In almost all of the studies presented here (as well as in most others not reported here) the chemical mixtures that produced unanticipated toxic effects contained at least one lipophile (K > 2.00) and one hydrophile ( CW < 2.00). The octanol water partition coefficients (7T w) are given in parentheses for each of the chemicals identified to point out the lipophilic and hydrophilic species. 

On-the-job exposures offer insight into the toxic effects of chemical mixtures. Though many health effects can be attributed to exposures to single chemicals, others cannot be accounted for by single chemical exposures and are clearly related to exposures to mixtures. This is particularly the case when at least one component of the mixture is a lipophile and at least one other component of the mixture is a hydrophile. The studies referenced in this chapter point out the need to consider mixture exposures when people present with symptoms, rather than dismiss their complaints as being of psychological origin. 

Cigarettes, cigars, pipe tobacco, and smokeless tobacco are made up of dried tobacco leaves and hundreds of other components added for flavor and other properties. More than 4000 individual toxic lipophilic and hydrophilic chemical compounds, of which greater than 60 are carcinogens, have been identified in tobacco and tobacco smoke. I35 36 Accordingly, all tobacco and tobacco smoke exposure is, of necessity, to mixtures of toxic chemicals. 

The effects of single chemicals on the respiratory system are discussed as background for an understanding of the effects of mixtures. As previously discussed in Section 2.3, unexpected chemical mixture exposure effects are observed when the mixtures contain at least one lipophilic and one hydrophilic chemical. This chapter addresses the effects of chemical mixtures on the respiratory system. Case studies from the literature with widely different mixture combinations are used to illustrate the effects noted. 

This section is devoted to chemical mixtures that are respiratory irritants. Irritants do not induce immunochemical responses, and irritation in non-sensitized individuals generally leads to slower, less serious respiratory responses and usually requires higher doses of toxicants to produce symptoms than in sensitized people. Irritant-induced inflammation responses (e.g., bronchial hyperactivity) can be severe and prolonged but, by definition, do not result in sensitization of those so exposed. Mixtures of lipo-philes and hydrophiles induce irritant respiratory system responses at concentration levels that are below those for the single chemicals. This phenomenon is well demonstrated by exposures in sick buildings. ... 

Exposures to sick buildings may stimulate respiratory responses in healthy individuals with no previous history of asthma, allergic rhinitis, chronic respiratory disease, recent acute respiratory illness, or extensive exposure to pollutants. Chemicals typically found in sick buildings arise from carpeting, paint, wood products, cleaners, and other sources. These chemicals are mixtures of lipophilic and hydrophilic chemicals and, with the exception of isocyanates from polyurethane wood finishes, are usually... 

Chemical mixtures that induce OA are almost exclusively combinations of hydrophiles and lipophiles. Table 17.6 contains a partial list of these mixtures. 46-52 Though the precise compositions of all of these chemicals are not given in the references cited, it is possible to extrapolate from the nature of the materials that they contain both hydrophiles and lipophiles. 

Cleaning products rank at or near the top of chemical mixtures that induce asthma. I5>3>1 These products are almost always mixtures of lipophiles and hydrophiles and are formulated that way to ensure maximum cleaning power. Chemicals contained in cleaning products include chlorine, acids, alkalis, glycol ethers, ammonia, ethanol, isopropanol, d-limonene, ionic and nonionic surfactants, ethanolamines, phenols, and others. 

The continuing worldwide increase in respiratory disease corresponds to increases in the release of chemicals into the atmosphere. Respiratory irritation, sensitization, asthma, RADS, and lung cancer can be attributed to numerous single chemicals whose toxicological properties are, for the most part, well known. Many unexplained incidences of respiratory disease cannot be attributed to single chemical exposures, but have been shown to occur when exposures are to chemical mixtures that are composed of at least one lipophile and one hydrophile. The sources of such mixtures include diesel exhausts, tobacco smoke, carpet emissions, paint fumes, and cleaning products. Prevention of chemically induced respiratory diseases should include limiting exposures to these chemical mixtures. 

The neurological health of painters has been extensively studied. Painters have been found to suffer from impaired behavioral effects, I86 87 93 sensory and sensorimotor neuropathies, t89l psychiatric function,I90,91,94 and learning and memory deficiency 92 problems. In the studies just cited, as well in many other similar ones, exposures were generally low level, occurring over a period of years, and exposures were to mixtures of lipophilic and hydrophilic chemicals. Other studies on exposures to single... 

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. 

In this study, neurological symptoms, including memory loss and reduced olfaction in the printers were found to increase with increasing levels of exposure. It is interesting to note that all exposure levels were below TLVs. The neurotoxic effects are attributed to the mixture of lipophilic and hydrophilic chemicals. The results of this study concur with a neurotoxic exposure case involving a printer exposed to the same chemicals that I investigated, but have not to date been published. In that case, the exposure levels to which the printer was exposed were more than an order of magnitude below the TLVs of all the chemicals. 

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. 

The compounds that have been identified as xenoestrogens vary widely in chemical nature. Many are highly lipophilic and slowly metabolized (TCDD, chlorinated hydrocarbon pesticides). Others are less lipophilic and more labile (phthalates) and some are hydrophilic (methyl paraben, aluminum chloride, and aluminum chlorohydrate). It is known that lipophilic chemicals are more readily absorbed through the skin than hydrophilic chemicals, but as has been pointed out repeatedly in this book, lipophiles facilitate the absorption of hydrophiles and contribute to unexplained mixture effects. Table 22.3 lists some of the known xenoestrogens, types of products they are used in, and their K)w values. 

As described in the earlier chapters of this book (Part 2), virtually each one of MCS triggering sources listed in Table 26.3 contains mixtures of lipophilic and hydrophilic chemicals. 

As discussed in Section 18.6, military personnel were administered PB and also exposed to DEET (an insect repellant) and permethrin (an insecticide), the combination of which produced unanticipated neurological symptoms. 621 When the exposures from diesel exhaust, oil well fire smoke, and spent munitions combustion products are added to these, the onset of other unexpected health effects are not surprising. It is to be noted that the chemical mixtures to which the military personnel were exposed to included large numbers of lipophilic and hydrophilic species. 

The exposure of skin to mixtures of lipophilic and hydrophilic chemicals leads to the increased absorption of the hydrophilic species. 12 The following studies are illustrative ... 

All the occupations listed in Table 28.2 carry with them exposures to mixtures of lipophilic and hydrophilic chemicals. Of the chemicals listed in Table 28.3, several are mixtures of compounds. These include gasoline, diesel fuel, mineral spirits, paint removers, paint thinners, and VM P naphtha. Though many of the studies referenced above consider organic solvents as only a mixture of lipophilic compounds, I13-1517 this is inappropriate, since many of the chemicals listed in Table 28.3 are mixtures of lipophiles and hydrophiles. For example, a typical solvent-based paint... 

As discussed above, paint removers are mixtures of lipophilic and hydrophilic chemicals formulated together to ensure maximum attack on paint. Paint thinners are generally composed of varnish makers and painters (VM P) naphtha and mineral spirits. VM P naphtha is a mixture of aliphatic alkanes and alkenes and aromatic hydrocarbons. Mineral spirits is a higher molecular weight composition of similar compounds. 

The animal studies just described serve as models for understanding hepatotoxicity of chemical mixtures in humans. Many case studies reporting hepatotoxicity of chemical mixtures in humans have been reported in the literature. The following are illustrative of these studies, which demonstrate the unanticipated hepatotoxic effects of mixtures of lipophiles and hydrophiles. Kqw values are included for each chemical to demonstrate lipophilic or hydrophilic character. 

The liver is essential in order to maintain life. Accordingly, xenobiotic attacks on it threaten life and well-being. Many chemicals are hepatotoxic, but mixtures of lipophilic and hydrophilic chemicals are liver toxins at exposure levels that are often far below those that are toxic for the single chemicals in those mixtures. Animal studies have demonstrated the... 

A cohort mortality study of petrochemical workers in Texas found an increased incidence of malignant brain tumors in workers who worked in a plant that used numerous lipophilic and hydrophilic chemicals and manufactured 43 refined chemicals, four major classifications of resins, four industrial gases, and a mixture of straight chain hydrocarbons J62l The cause of the observed cancers was not determined. 

All can be attributed to exposures to chemical mixtures that contain at least one lipophile and at least one hydrophile. 

Most cancer cluster studies have focused on identifying single compound causative agents. Most of these clusters, however, result from exposures to mixtures of chemicals. Analysis of the cancer clusters reported in the literature, many of which are described above, reveals that all of the unexplained clusters ensue following exposures to chemical mixtures that contain at least one lipophilic and one hydrophilic chemical. These mixtures act as unique entities to produce specific cancer clusters whose locations are not predicted by the known toxicology of the single compounds that comprise the mixtures. 

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