PRINCIPLES OF TOXICOLOGY - Biology East Borneo

402 PROPERTIES AND EFFECTS OF ORGANIC SOLVENTSFigure 16.29 Benzidine.Figure 16.30 Hydrazine.carcinogen and exhibits mutagenic potential in the bacterial tests. The USEPA has established acarcinogenic potency factor (CPF) of 0.067 (mg/kg⋅day) –1 for inhalation exposure and 0.0067(mg/kg⋅day) –1 for oral exposure. Although benzidine is one of the compounds regulated by OSHA asa human carcinogen, no exposure standards or recommendations have been set by OSHA or ACGIH.Other Nitrogen CompoundsBecause of its strong reducing capabilities, hydrazine (see Figure 16.30) is used in a wide range ofindustrial chemical syntheses, photographic processes, and metallurgy. At sufficient concentration,hydrazine is a strong skin and mucus membrane irritant, convulsant, hepatotoxin, and a moderatehemolytic agent. It is readily absorbed through the lungs, the gastrointestinal tract, and through intactskin, as evidenced by the fact that equivalent median lethal doses are observed in animal studiesfollowing oral, intravenous, and intraperitoneal administration. The effects noted after absorption byall routes include anorexia, weight loss, weakness, vomiting, excitement, and convulsions. Airborneexposure may produce eye and respiratory tract irritation, lung congestion, bronchitis, and pulmonaryedema.Hydrazine has been shown to be tumorigenic in mice, where lungs are the primary target organs.A carcinogenic potency factor (CPF) or slope factor (SF) of 17.1 (mg/kg⋅day) for inhalation exposure,and 3.0 (mg/kg⋅day) for oral exposure, has been established by USEPA. This compound has also shownto be mutagenic in phage, bacteria, plants, Drosophila, and mammalian test systems. The ACGIHTLV ® and the OSHA PEL for hydrazine have been set at 0.01 ppm and 1.0 mg/m 3 , based on observationof damage to lung, liver, and kidney tissue at higher exposure levels.16.15 TOXIC PROPERTIES OF REPRESENTATIVE ALIPHATIC AND AROMATICNITRO COMPOUNDSThese compounds have little industrial use and in general are oily liquids of low solubility and volatility.Toxicologically, they can be classified as moderate irritants, because their anesthetic symptoms aremild. Unsaturated compounds may be absorbed via the skin to a significant extent, while the saturatedchemicals are not. Halogenation produces definite skin irritation, some systemic absorption and,therefore, toxicity. Aromatic nitro compounds are a class of chemicals, several members of which mayproduce methemoglobin formation and/or sensitization to the compound.Nitro derivatives of benzene and toluene also have prominent toxic effects other than sensitization,CNS depression, or methemoglobinemia. The trinitrotoluene or dinitrobenzene compounds are wellabsorbed by all routes of exposure. These compounds can uncouple oxidative phosphorylation, andliver injury is often seen along with the toxicities previously mentioned. Other problems that have been