Chlorobenzene

IDENTIFICATION AND USE: Chlorobenzene is a colorless liquid with a characteristic penetrating, almond-like odor. It is used as an Intermediate in the manufacture of chloronitrobenzenes, oxide, DDT, and silicones; as a process solvent for methylene diisocyanate, adhesives, polishes, waxes, pharmaceutical products, paints, and natural rubber; as a degrading solvent; heat transfer medium; in textile processing; and tar and grease remover. HUMAN EXPOSURE AND TOXICITY: Dermal exposure to chlorobenzene for 1 hour resulted in burning pain, hyperemia, whealing, and erythema formation at the application site. Twelve hours postexposure, a minimal local vesiculation was seen. Continuous contact for a week may result in moderate erythema and slight superficial necrosis. Clinical symptoms included hyperpnea, ataxia, labored breathing, prostration, and death from respiratory paralysis. Humans occupationally exposed to chlorobenzene intermittently for up to 2 years at levels above current federal limits displayed signs of neurotoxicity including numbness, cyanosis (from depression of respiratory center), hyperesthesia, and muscle spasms. Early complaints included headache and irritation of the upper respiratory tract and mucosa of the eyes. Clinical examination of workers exposed to chlorobenzene in the manufacture of polyvinyl chloride showed that some workers reported nerve lesions, hepatitis, chronic gastritis with gastric juice hypoacidity, and bronchitis. Severe anemia and medullary aplasia in a 70 year old woman was related to her employment in hat making, which required the use of glue containing 70% chlorobenzene. A 2 year old boy swallowed 5 to 10 mL of Puran, a cleaning agent containing chlorobenzene and 2.5 hr after ingestion, lost consciousness and suffered vascular paralysis and heart failure. He survived, and the odor of chlorobenzene was present in breath and urine for 5 to 6 days. ANIMAL STUDIES: Chlorobenzene is lethal following acute, intermediate, and chronic oral exposures in animals. Neurological effects of chlorobenzene have also been reported in animals following inhalation. Acute inhalation exposure produced muscle spasms followed by /CNS depression/ in rabbits exposed to 5 mg/L chlorobenzene (1,090 ppm) or greater for 2 hours. Dermal contact resulted in moderate skin and eye irritant (tested in the guinea pig and rabbit, respectively). Single ip injections of chlorobenzene in rats resulted in time- and dose-dependent hepatotoxicity, including liver necrosis, increased liver weights, and increased serum enzyme activities with dose-dependent recovery. Systemic effects of single ip injections of chlorobenzene also included damage to the kidney, effects on bile and pancreatic flow, increased alanine aminotransferase (ALT) and centrilobular necrosis. Death occurred within 2 to 3 days after a single exposure to 4,000 mg/kg in corn oil by gavage in rats of both sexes, and in mice after a single exposure to 1,000 mg/kg. Administration of chlorobenzene by gavage resulted in dose-dependent chemical induced injuries to the liver (centrilobular hepatocellular degeneration and necrosis), kidney (necrosis of the proximal tubular epithelium), bone marrow (myeloid depletion), spleen (lymphoid depletion or necrosis) and thymus at doses > or = 250 mg/kg. Male and female mice exposed to chlorobenzene at 2500 mg/cu m daily, 7d/wk for 3 weeks showed loss of appetite, general emaciation, marked somnolence and weight loss; 5 animals died. Autopsy revealed fatty degeneration in the liver, leading to acute yellow atrophy. The majority of mice showed a decrease in white blood cell number with relative decrease in neutrophils and relative increase in lympocytes. Chronic exposure of mice to chlorobenzene at 100 mg/cu m daily for 3 months, showed increased agitation and motility and decreased white blood cell count with relative decrease in neutrophils and relative increase in lymphocytes. In a two-generation study in rats, chlorobenzene in concentrations up to 450 ppm did not adversely affect reproductive performance or fertility. Chlorobenzene was not mutagenic for Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 or TA1538, with or without addition of rat liver or hamster liver homogenate. Chlorobenzene did not induce DNA damage in Escherichia coli strains WP2 uvr A+ rec A+ or WP100 uvr A- rec A- or S. typhimurium strains TA1978 uvr B+ or TA1538 uvr B-. Slight leukopenia and lymphocytosis occurred in mice exposed to chlorobenzene (0.1 mg/L) for 3 months. ECOTOXICITY STUDIES: Chlorobenzene was less hepatotoxic to trout than rats. This difference could not be totally accounted for by reduced absorption in trout. Chlorobenzenes caused significant increases in serum testosterone concentration in the crucian carps compared to the controls.