Dichlorobenzenes, toxicities

Because 1,4-dichlorobenzene is a liver toxin, it probably can interact with other chemicals that are liver toxicants. These toxicants are many, and include ethanol, halogenated hydrocarbons (chloroform, carbon tetrachloride, etc ), benzene, and other haloalkanes and haloalkenes. In addition, 1,4-dichlorobenzene toxicity may also be exacerbated by concurrent exposure with acetaminophen, heavy metals (copper, iron, arsenic), aflatoxins, pyrrolizidine alkaloids (from some types of plants), high levels of vitamin A, and hepatitis viruses. Such interactions could either be additive or S5mergistic effects. 

Solubility and Solvent Resistance. The majority of polycarbonates are prepared in methylene chloride solution. Chloroform, i7j -l,2-dichloroethylene, yy -tetrachloroethane, and methylene chloride are the preferred solvents for polycarbonates. The polymer is soluble in chlorobenzene or o-dichlorobenzene when warm, but crystallization may occur at lower temperatures. Methylene chloride is most commonly used because of the high solubiUty of the polymer (350 g/L at 25°C), and because this solvent has low flammabiUty and toxicity. Nonhalogenated solvents include tetrahydrofuran, dioxane, pyridine, and cresols. Hydrocarbons (qv) and aUphatic alcohols, esters (see Esters, organic), or ketones (qv) do not dissolve polycarbonates. Acetone (qv) promotes rapid crystallization of the normally amorphous polymer, and causes catastrophic failure of stressed polycarbonate parts. 

This includes bioremediation cases of contaminated sites with several toxic and carcinogenic pollutants, such as petroleum hydrocarbons, PAHs, dichlorobenzene, chlorinated hydrocarbons, carbon tetrachloride, Dicamba, methyl bromide, trinitrotoluene, silicon-based organic compounds, dioxins, alkyl-phenol polyethoxylates, nonylphenol ethoxylates, and polychlorinated biphenyls. The following is a brief summary of each case. 

The experimental first-order decay rate for pentachlorobenzene in an aqueous solution containing a nonionic surfactant micelle (Brij 58, a polyoxyethylene cetyl ether) and illuminated by a photoreactor equipped with 253.7-nm monochromatic UV lamp is 1.47 x lO Vsec. The corresponding half-life is 47 sec. Photoproducts reported include all tetra-, tri-, and dichlorobenzenes, chlorobenzene, benzene, phenol, hydrogen, and chloride ions (Chu and Jafvert, 1994). Chemical/Physical. Emits toxic chlorinated acids and phosphene when incinerated (Sittig,... 

The primary purpose of this chapter is to provide public health officials, physicians, toxicologists, and other interested individuals and groups with an overall perspective of the toxicology of 1,4-dichlorobenzene. It contains descriptions and evaluations of toxicological studies and epidemiological investigations and provides conclusions, where possible, on the relevance of toxicity and toxicokinetic data to public health. 

Deseriptive data are available from reports of humans exposed to 1,4-diehlorobenzene by inhalation (and possibly dermal contact). It is important to note that the case studies discussed in this section should be interpreted with caution since they reflect incidents in which individuals have reportedly been exposed to 1,4-dichlorobenzene, and they assume that there has been no other exposure to potentially toxic or infectious agents. There is usually little or no verification of these assumptions. Case studies in general are not scientifically equivalent to carefiilly designed epidemiological studies or to adequately controlled and monitored laboratory experiments. Thus, the case studies described below should be considered only as providing supplementary evidence that 1,4-dichlorobenzene may cause the reported effects. 

Other intermediate-duration oral studies with 1,4-dichlorobenzene have reported liver toxicity. In female rats dosed with 1,4-dichlorobenzene by gavage for about 6 months, doses of 188 mg/kg/day and above resulted in increased liver weights. At 376 mg/kg/day, slight cirrhosis and focal necrosis of the liver were also observed (Hollingsworth et al. 1956). No effects on the liver were seen at a dose of 18.8 mg/kg/day. Based on a minimal LOAEL (increased liver weight) of 188 mg/kg/day, an intermediate-duration MRL of 0.4 mg/kg/day was calculated as described in the footnote to Table 2-2 and Appendix A (Hollingsworth et al. 1956). 

Studies of the hepatic effects of chronic 1,4-dichlorobenzene exposure are sparse. The toxicity of... 

In a study designed to investigate the mechanism of renal toxicity for 1,4-dichlorobenzene reported in the NTP (1987) studies, 1,4-dichlorobenzene administered by gavage to male Fischer 344 rats at 7 daily doses of 120 or 300 mg/kg/day significantly increased the level of protein droplet formation in the kidneys of males but not females (Charbonneau et al. 1987). Administration of a single dose of... 

In chronic-duration toxicity studies in laboratory animals, Hollingsworth et al. (1956) found no evidence of cataract formation in rabbits administered a total of 263 doses of 500 mg/kg/day 1,4-dichlorobenzene in olive oil over a 367-day period. 

Cytogenetic effects were not found in bone marrow cells from mice treated with 1,4-dichlorobenzene by gavage at levels up to 1,800 mg/kg/day in a 13-week study (NTP 1987). No increase in micronucleated cells occurred even at levels that were extremely toxic to the test animals, resulting in liver toxicity and decreased survival rates. As noted by the authors of that study, the observed carcinogenic activity of... 

The MRL was based on liver toxicity rather than kidney toxicity because the effects of 1,4-dichlorobenzene on the kidneys of male rats are associated with the occurrence of hyaline droplets from 2. -globulin and are not applicable to humans (EPA 1991i). 

Hepatic Effects. Liver effects reported in case studies in humans exposed to 1,4-dichlorobenzene via inhalation have included jaundice, cirrhosis, and atrophy (Cotter 1953). Estimates of exposure duration ranged from 1 to 18 months however, quantitative data on 1,4-dichlorobenzene levels were not available. One report was located that described a 3-year-old boy who may have ingested 1,4-dichlorobenzene crystals. Jaundice was reported, indicating that liver function was in some way compromised, although no further details were reported. No dermal exposures to 1,4-dichlorobenzene in humans were reported. The lack of reliable information regarding human exposures to 1,4-dichlorobenzene by all three routes of exposure makes it difficult to draw any helpful conclusions about the toxicity of 1,4-dichlorobenzene in humans. 

There is little credible scientific information available on the susceptibility and toxicological effects of 1,4-dichlorobenzene in children. The risk for exposure is apparently high. A study by Hill et al. (1995) measured blood levels of 1,4-dichlorobenzene and urine levels of its metabolites in 1,000 adults, finding that exposure to 1,4-dichlorobenzene was widespread, with 98% of the adults having measurable concentrations of 1,4-dichlorobenzene metabolites in their urine. There is no evidence to indicate that children are likely to be exposed to lower amounts of 1,4-dichlorobenzene from everyday living, suggesting that children are perhaps equally at risk for exposure and potential toxic side-effects. 

Several chlorophenols, including 2,5-dichlorophenol, have been identified in laboratory animals exposed to lindane. This indicates that the presence of 2,5-dichlorophenol is fairly specific, but not completely specific, for 1,4-dichlorobenzene exposure. Information on the analytical methods commonly used to detect and quantify 1,4-dichlorobenzene in biological samples is presented in Section 6.1. There are currently no data available to assess a potential correlation between the values obtained with these measurements and the toxic effects observed in humans or laboratory animal species. 

A susceptible population will exhibit a different or enhanced response to 1,4-dichlorobenzene than will most persons exposed to the same level of 1,4-dichlorobenzene in the enviromnent. Reasons may include genetic makeup, age, health and nutritional status, and exposure to other toxic substances (e g., cigarette smoke). These parameters may result in reduced detoxification or excretion of 1,4-dichlorobenzene, or... 

This section will describe clinical practice and research concerning methods for reducing toxic effects of exposure to 1,4-dichlorobenzene. However, because some of the treatments discussed may be experimental and unproven, this section should not be used as a guide for treatment of exposures to... 

No information was available that described specific methods for reducing peak absorption following exposure, reducing body burden, interfering with the mechanism of action of toxic effects, or reducing toxic effects in children exposed to 1,4-dichlorobenzene. The following texts provide specific information about treatment following exposures to 1,4-dichlorobenzene ... 

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