Chlorobenzene, toxicity

No studies were located regarding human populations that are unusually susceptible to chlorobenzene. By analogy to other lipophilic chlorinated benzenes such as hexachlorobenzene, which is found in human milk (Weisenberg et al. 1985), nursing infants may be susceptible to chlorobenzene toxicity. 

Intermediate-Duration Exposure. No studies are available in humans on the effects of intermediate-duration exposure to chlorobenzene by any route. Inhalation and oral studies in animals indicate that the nervous system, liver, and kidneys are principal target tissues following exposure to chlorobenzene. An intermediate oral MRL was derived based on liver effects in rats. There are no data on effects following dermal exposure in animals. Because there is potential for exposure to chlorobenzene through skin contact, additional studies by dermal exposure would add to the database on chlorobenzene toxicity. 

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. 

Chlorobenzenes are stable compounds and decompose slowly only under excess heating at high temperatures to release some HCl gas and traces of phosgene. It is possible, under certain limited conditions of incomplete combustion or pyrolysis, to form polychlorinated dibenzo-/)-dioxins (PCDDs) and dibenzofurans (PCDFs) from chlorobenzenes (Cm OROCARBONS and cm OROHYDROCARBONS, toxic aromatics). 

In general, all of the chlorobenzenes are less toxic than benzene. Liquid chlorobenzenes produce mild to moderate irritation upon skin contact. Continued contact may cause roughness or a mild bum. SoHds cause only mild irritation. Absorption through the skin is slow. Consequently, with short-time exposure over a limited area, no significant quantities enter the body. 

The data from some single-dosage oral toxicity tests, expressed as LD q, are reported in Table 4. The values reported on the order of 1 g/kg or greater indicate a low acute oral toxicity. In animals, continued ingestion of chlorobenzenes over a long time can cause kidney and Hver damage. 

Toxicity to fish is included in the data Hsted in Table 4. Marine life, particularly fish, may suffer damage from spills in lakes and streams. The chlorobenzenes, because they are denser than water, tend to sink to the bottom and may persist in the area for a long time. However, some data indicate that dissolved 1,2,4-trichlorobenzene can be biodegraded by microorganisms from wastewater treatment plants and also has a tendency to slowly dissipate from water by volatilization (34). 

NOTE - Petrochemical plants also generate significant amounts of solid wastes and sludges, some of which may be considered hazardous because of the presence of toxic organics and heavy metals. Spent caustic and other hazardous wastes may be generated in significant quantities examples are distillation residues associated with units handling acetaldehyde, acetonitrile, benzyl chloride, carbon tetrachloride, cumene, phthallic anhydride, nitrobenzene, methyl ethyl pyridine, toluene diisocyanate, trichloroethane, trichloroethylene, perchloro-ethylene, aniline, chlorobenzenes, dimethyl hydrazine, ethylene dibromide, toluenediamine, epichlorohydrin, ethyl chloride, ethylene dichloride, and vinyl chloride. 

The structural range of industrially important representatives of these groups is enormous, and includes chlorobenzenes (solvents), polychlorinated biphenyls (PCBs) (hydraulic and insulating fluids), and polybrominated biphenyls and diphenyl ethers (flame retardants). There is widespread concern over both the persistence and the potential toxicity of all these compounds, and sites that have become contaminated during their production represent a threat both to the environment and to human health. Pathways for the aerobic bacterial degradation of chlorobenzenes and chlorobiphe-nyls, and their brominated analogs have been discussed in Chapter 9, Part 1. 

There are several theories concerning the mechanism by which the toxic component of a contact insecticide exerts its action. The toxicity has been credited to the condensed chlorobenzene system, which is also lipophilic in character (70). 

Carlson, A.R., Kosian, P.A. (1987) Toxicity of chlorobenzenes to fathead minnows (pimephales promelas). Arch. Environ. Contam. Toxicol. 16, 129-135. 

Michielsen, C.C., van Loveren, H., and Vos, J.G.,The role of the immune system in hexa-chlorobenzene-induced toxicity. Environ. Health. Perspect., 107, Suppl 5, 783, 1999. 

These indices have been used to study the reactivity for a series of chlorobenzenes and a good correlation is observed, for example, between W and toxicity of chlorobenzene [41]. For a detail discussion of this concept and its applications, we refer the readers to a recent review [41,42]. For studying intramolecular reactivity, these philicity indices and local softness contain the same information as obtained from the Fukui functions, because they simply scale the Fukui functions. In some cases the relative electrophilicity and relative nucleophilicity may be used although they provide similar trends as s(r) and co(r) in most cases [43]. In the same vein, the spin-donicity and spin-philicity, which refer to the philicity of open-shell systems [44], could also be utilized to unravel the reactivity of high-spin species, such as the carbenes, nitrenes, and phosphinidenes [45]. 

Toxic fumes of phosgene and hydrogen chloride may form when exposed to an open flame (CHRIS, 1984). Chlorobenzene is stable up to 700 °C but in combination with other chlorinated compounds, it is stable up to 900 °C (Graham et al, 1986). 

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,... 

Boyd, E.M., Meharg, A.A., Wright, J., and Killham, K. Toxicity of chlorobenzenes to a /ux-marked terrestrial bacterium. Pseudomonas fluorescens. Environ. Toxicol. Chem., 17(11) 2134-2140, 1998. 

Calamari, D., Galassi, S., Setti, F., and Vighi, M. Toxicity of selected chlorobenzenes to aquatic organisms. Chemosphere, 12(2) 253-262, 1983. 

Van Gestel, C.A.M. and Ma, W.-C. Development of QSAR s in soil ecotoxicology earthworm toxicity and soil sorption of chlorophenols, chlorobenzenes and chloroanilines. Water, Air, SoilPollut, 69(3-4) 265-276, 1993. 

Fisher R, Smith PF, Sipes IG, et al. 1990. Toxicity of chlorobenzenes in cultured rat liver slices. 

Rautio AW. 1988. Chlorobenzene Producers Association comments on the Draft Toxicological Profile for 1,4-Dichlorobenzene. Submitted to the Agency for Toxic Substances and Disease Registry, March 7, 1988. 

Watanabe T, Ishihara N, Ikeda M. 1976. Toxicity of and biological monitoring for 1,3-diamino-2,4,6-trinitrobenzene and other nitro-amino derivatives of benzene and chlorobenzene. Int Arch Occup Environ Health 37 157-168. 

Agency for Toxic Substances and Disease Registry (ASTDR) Toxicological Profile for Chlorobenzene. US Department of Health and Human Services, Public Health Service, TP-90-06, 1990... 

Another development is due to the interest in polychlorodibenzofurans, spurred by their occurrence as environmental contaminants. Polychloro-phenols are manufactured in large amounts (150,000 tons per annum) and find a wide range of uses. The usual method of manufacture involves the hydrolysis of chlorobenzenes, and side reactions, favored by high temperature, can lead to the production of polychlorodibenzofurans and poly-chlorodibenzo-p-dioxins. The Seveso incident is well known." Polychloro-biphenyls are also widely used industrial chemicals, particularly in heat exchange systems, and their pyrolysis leads to the formation of polychloro-dibenzofurans. Polychlorodibenzofurans have also been detected in the fly ash and flue gases of incinerators and industrial heating plants. The most toxic of the polychlorodibenzofurans are 2,3,7,8-tetra-, 1,2,3,7,8-penta-, and 2,3,4,7,8-pentachlorodibenzofuran, and an extensive literature exists on the environmental pollution and the results of human exposure to these substances. A particularly tragic example of the latter occurred in 1968 in the Fukuoka prefecture of Japan after consumption of rice oil contaminated with a commercial polychlorobiphenyl. 

Preliminary results in the validation of a novel short term test. Mutat. Res., 46, 305-310 Watanabe, T., Ishihara, N. Ikeda, M. (1976) Toxicity of and biological monitoring for 1,3-diamino-2,4,6-trinitrobenzene and other nitro-amino derivatives of benzene and chlorobenzene. Int Arch, occup. environ. Health, 37, 157-168 Yoshimi, N., Sugie, S., Iwata, H., Niwa, K., Mori, H., Hashida, C. Shimizu, H. (1988) The genotoxicity of a variety of aniline derivatives in a DNA repair test with primary cultured rat hepatocytes. Mutat. Res., 206, 183-191... 

Less commonly used solvents include methyl ethyl ketone, b.p. 80° ethylene chloride, b.p. 84° dioxan (diethylene dioxide), b.p. 101° (vapours are toxic) toluene, b.p. 110° pyridine, b.p. 115-5° chlorobenzene, b.p. 132° cellosolve (ethylene glycol monoethvl ether), b.p. 134-5° di- -butyl ether, b.p. 141° s-tetrachloro-... 

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