Health and Environmental Effects Profile for Pentachloronitrobenzene

Pure pentachloronitrobenzene (PCNB) is a colorless crystalline solid (Worthing, 1983). The commercial product may have a light- yellow to cream color with a musty odor (Hartley and Kidd, 1983). It is practically insoluble in a number of organic solvents. The compound is reasonably stable but may undergo hydrolysis in a strong alkaline medium (Hartley and Kidd, 1983). In 1983, Olin Corp., Leland, MS, was the only manufacturer of PCNB in the United States (SRI, 1984; Hartley and Kidd, 1983). No data for U.S. production volume for this chemical are available, but recent production source data (USITC, 1985; SRI, 1985) suggest that this chemical is no longer commercially produced in the United States. The primary usage of PCNB is as a soil fungicide for a wide variety of crops and in seed treatment (Worthing, 1983; Hartley and Kidd, 1983). The fate of PCNB in water has not been comprehensively studied. Only qualitative data regarding fate and transport in water are available. The half-life of PCNB in the water phase was estimated to be 1.8 days. The two processes reported to be most responsible for the rapid decrease in PCNB concentration in water were volatil ization and sorption to seston and biota, followed by sedimentation as detritus (Schauerte et al., 1982). Neither biodegradation nor photolysis appears to be a significant process for the loss of PCNB from water (Crosby and Hamadmad, 1971; Schauerte et al., 1982). The BCFs for PCNB in the golden orfe, Leucisens idus melanotus, and in rainbow trout, Salmo gairdneri, were reported to be 950- 1130 and 260-590, respectively (Korte et al., 1978; Oliver and Niimi, 1985). It therefore appears that PCNB will moderately bioaccumulate in aquatic organisms. Pertinent data regarding the fate and transport of PCNB in air could not be located in the available literature as cited in the Appendix. Based on its physical properties and its behavior in other media, it would appear that PCNB will persist in the atmo sphere because no known chemical/photochemical processes signif icantly degrade this chemical. Precipitation of particulate PCNB, especially of larger particle size and higher particle density, may remove some PCNB from the atmosphere. PCNB is persistent in soils. The two processes that are important in the loss of PCNB from soils are volatilization and biodegradation; biodegradation is more rapid in soils under anaerobic conditions than under aerobic conditions (Ko and Farley, 1969; Casley, 1968; Gile and Gillett, 1979; Cole and Metcalf, 1977). The average half- life of PCNB in a variety of field soils was reported to be 434 days (Beck and Hansen, 1974). Another study reported the half-lives for PCNB in sandy loam, clay and peaty muck soils as 4.7, 7.6 and 9.7 months, respectively (Wang and Broadbent, 1972). PCNB is expected to be moderately mobile in soils (Gile and Gillett, 1979). Evidence of very restricted (∼ 3% on the average) translocation of PCNB and its metabolites from the roots to foliar tissue in plants was reported by Cairns et al. (1983). Pertinent data regarding the levels of PCNB in ambient and drink ing water could not be located in the available literature as cited in the Appendix. U. S. EPA's STORET database contains 120 entries on the analysis of PCNB in ambient water and aqueous effluent samples. Maximum and minimum PCNB concentrations in these samples were 1.0 and 0.01 μg/l, respectively, with a mean value of 0.4 μg/l. Pertinent data regarding the ambient atmospheric level of PCNB could not be located in the available literature as cited in the Appendix. The concentration of PCNB in the ambient air of a commercial pest control building was reportedly 1.56 μg/m 3 (Yeboah and Kilgore, 1984). In the foods consumed by U.S. adults, infants and toddlers, PCNB residues have been detected mainly in the oils, fats and shortening group of foods (Johnson et al., 1981a,b, 1984a; Johnson and Manske, 1976; Manske and Johnson, 1975; 1984a,b). Occasionally, PCNB has been detected in sugar and adjuncts, fruits and potatoes (Manske and Johnson, 1977; Johnson and Manske, 1977; Podre barac, 1984a). On the basis of the assumption of a maximum PCNB content of 0.006 mg/kg (Johnson et al., 1984a) in oil, fats and shortening composite and a daily adult consumption of 0.070 kg/day of this category of food (Johnson et al., 1984a), the maxi mum daily adult intake of PCNB in the United States has been estimated to be 0.4 μg. The Canadian daily PCNB intake has been reported to vary between 0 and 0.4 μg (McLeod et al., 1980). Little pertinent information is available concerning toxicity of PCNB to aquatic organisms in the available literature. PCNB tox icity to carp increased with increasing temperature, with 24-hour LC 50 values ranging from 40 mg/l at 15° C to 1 mg/l at 35° C (Hashimoto and Nishiuchi, 1981). The lowest concentration at which toxic effects were reported for any species was 1 mg/l. PCNB and its metabolites can apparently accumulate to a signifi cant extent in fish and other aquatic biota. In the species that have been studied, PCNB metabolism involves denitrification but not dechlorination (Bahig et al., 1981; Murphy et al., 1982). Pharmacokinetic and metabolism studies of PCNB indicate that it is rapidly and extensively absorbed from the gastrointestinal tract of rabbits, rats and monkeys (Betts et al., 1955; Korte et al., 1978; Koegel et al., 1979a,b). Following absorption by monkeys and rats, PCNB is rapidly metabolized and the metabolites are widely dis tributed to tissues but do not accumulate (Koegel et al., 1979a,b; Borzelleca et al., 1971). Courtney et al. (1976) demonstrated that PCNB and its metabolites can cross the placental barrier of mice. Major metabolites in urine and feces of monkeys and rats include pentachloroaniline, pentachlorothionanisole, pentachlorobenzene, pentachlorophenol, pentachlorothiophenol and mercapturic acid conjugates (Borzelleca et al., 1971; Koegel et al., 1979c). Metabolic pathways in monkeys involve reduction of the nitro group to pen tachloroaniline and conjugation with glutathione. Conjugation twice with the same molecule of PCNB can lead to bis methylmercapto-tetrachlorobenzene and other tetrachlorometabo lites. Conjugation and nitro reduction combined can lead to tetrachloroaminometabolites. Similar pathways may operate in rats. The metabolites are excreted in the urine and bile. Biliary excretion accounts for the fecal metabolites. Unchanged PCNB was excreted only in the feces of monkeys. The rate of excretion of PCNB and metabolites was dose-dependent: 50% was excreted in 24 hours following a dose of 0.5 mg/kg; and 50% was excreted in 4 days following a dose of 91 mg/kg. There have been five chronic bioassays involving dietary adminis tration of PCNB. BRL (1968a) administered an average concentra tion of 1298 ppm PCNB to 18 male and 18 female B6C3F1 and B6AKF1 mice for 77 weeks. Courtney et al. (1976) later confirmed that the sample was contaminated with 11% hexachlorobenzene (HCB). The only positive neoplastic results were increased inci dences of hepatomas in female B6C3F1 and male B6AKF1 mice (p < 0.001), compared with negative controls. Cabral et al. (1977, 1978), however, noted increased incidences of this tumor type in hamsters treated with 50-200 ppm and mice treated with ≥ 100 ppm HCB alone in the diet. NCI (1978) administered 97% PCNB to 50 male and 50 female Osborne-Mendel rats and B6C3F1 mice for 78 weeks, at two die tary levels. Average concentrations for the low-dose rats were 5417 ppm (males) and 7875 ppm, (females), and for the high-dose rats were 10, 064 ppm (males) and 14,635 ppm (females). Average con centrations for the low-dose mice were 2606 ppm (males) and 4093 ppm (females), and for the high-dose mice were 5213 ppm (males) and 8187 ppm (females). Compared with control groups of 20 rats each, the treated rats showed no significant increases in tumor inci dence. Among the mice, low-dose males and high-dose females did not show any significant (by the Fisher exact test) elevations in hepatocellular carcinomas over control rats. These results were especially difficult to evaluate because of the small number of male mice that survived to terminal sacrifice and the large number of tissue sites that were autolyzed in female mice. In a repeat study by NTP (1986) that used highly purified PCNB (> 99% PCNB, 0.07 ± 0.01% HCB), B6C3F1 mice were given the compound in the diet at 2500 or 5000 ppm for 103 weeks. No evidence of carcinogenicity was found, although high mortality in the treated female mice decreased the sensitivity of the study. Two oral chronic bioassays using technical grade PCNB were per formed in Swiss mice (Van der Heijden and Til, 1974) and albino rats (Anonymous, n.d.). The compound was administered for 80 weeks (mice) and 104 weeks (rats), at 0, 100, 400 or 1200 ppm. In high-dose female mice there were increased (p < 0.001) incidences of fibrosarcomas and combined fibromas/fibrosarcomas (p < 0.001), relative to control values. By employing Cochran-Armitage trend tests, statistically significant (p < 0.001) differences were observed in female mice for these tumor types. In male mice, there was suggestive evidence of a treatment-related increase in liver nodules, which was probably a hyperplastic rather than a neoplas tic effect. In rats of either sex, there appeared to be no treatment- r