CAS No. 583-78-8
Metabolite of 1,4-Dichlorobenzene (Paradichlorobenzene)
The chemical 2,5-dichlorophenol is a metabolite of 1,4-dichlorobenzene (paradichlorobenzene), which has been used in moth balls, room and toilet deodorizers, and previously, as an insecticidal fumigant. Industrial uses include synthesis of dyes and other chemicals and certain resins. Paradichlorobenzene has been detected in ambient air in households, bathrooms, and new buildings (Dodson et al., 2007; Saijo et al., 2004) and in exhaled breath samples of persons living in households where room deodorizers and moth crystals were used (Wallace et al, 1987). 2,5-Dichlorophenol can also be formed in waste water treatment, wood pulp processing, and during the incineration of wood, coal, and municipal waste (HSDB, 2009).
Because paradichlorobenzene volatilizes easily, inhalation is a major exposure route. Dermal absorption can also occur, especially in workplaces where either paradichlorobenzene or 2,5-dichlorophenol is manufactured or processed. General population exposure to 2,5-dichlorophenol occurs mainly via the metabolism of inhaled paradichlorobenzene (Hill et al., 1995a).
Paradichlorobenzene can be absorbed through oral, dermal, or pulmonary exposure routes. Once it is absorbed in the body, paradichlorobenzene is metabolized largely to 2,5-dichlorophenol, then conjugated to glutathione and excreted in the urine over several days (Hissink et al., 1997; Pagnotto and Walkley, 1965). The levels of 2,5-dichlorophenol in urine and paradichlorobenzene in blood or in ambient air are highly correlated in the general population (Hill et al 1995a; Yoshida et al., 2002).
Chronic inhalation of paradichlorobenzene resulted in kidney and liver damage in laboratory animals (IARC, 1999). Chronic feeding studies in laboratory animals resulted in liver and kidney tumors and in pregnant animals, reduced weight gain but no effects on the offspring (IARC, 1999). Results of in vitro testing indicated that neither paradichlorobenzene nor 2,5-dichlorophenol were genotoxic (Tegethoff et al., 2000). Eye and respiratory irritation may occur at high air concentrations, as in workplaces where paradichlorobenzene is manufactured or processed. Workers with chronic exposure had slightly increased serum transaminase values and white blood cell counts (Hsiao et al., 2009). Liver necrosis occurred in individuals after prolonged exposure to high concentrations of paradichlorobenzene (Cotter, 1953).
The NTP (2010) and IARC (1999) consider that paradichlorobenzene is reasonably anticipated to be a human carcinogen. IARC (1999) considers that combined exposures to polychlorophenols or to their sodium salts are possibly carcinogenic to humans. Information about external exposure (i.e., environmental levels) and health effects is available from the ATSDR's toxicological profiles at: https://www.atsdr.cdc.gov/substances/toxsubstance.asp?toxid=126.
Urinary levels of 2,5-dichlorophenol reflect recent exposure. Median levels of urinary 2,5-dichlorophenol during three NHANES survey periods (2003-2008) ranged from 6.6 to 10.4 µg/L in adults, or about three to four times lower than in a subsample of NHANES III (1988-1994) adult participants (Hill et al., 1995a and 1995b). In NHANES 2009-2010, the median urinary 2,5-dichlorophenol or 4.6 µg/L was more than six times lower than in the NHANES III subsample. In a 1989 study of Arkansas children, the median urinary 2,5-dichlorophenol was 9 µg/L, about 3 times lower than the median value in an adult subsample from NHANES III, which was conducted around the same time (Hill et al, 1989, 1995a, and 1995b). Pregnant women living in an agricultural region of California had urinary 2,5-dichlorophenol levels measured in the second and third trimesters, with median values of 21.5 and 18.5 µg/L and 95th percentile values of 1935 and 1950 µg/L, respectively (Castorina et al., 2010). In 1998, a sample of the adult German population had median urinary 2,5-dichlorophenol levels that were about seven times lower than in U.S. adults (Becker et al., 2003; CDC, 2012). In contrast, a small study of Japanese adults with non-occupational exposure to paradichlorobenzene determined by personal air monitoring reported average urinary 2,5-dichlorophenol levels that ranged from 537-797 µg/L (Yoshida et al., 2002).
Workers exposed to paradichlorobenzene have had urinary 2,5-dichlorophenol levels that were much higher than levels found in the general population (Hsiao et al., 2009). At a mean air concentration of 25 parts per million (ppm), the corresponding urinary level of 2,5-dichlorophenol was 50,000 µg/g creatinine (Pagnotto and Walkley, 1965).
Finding a measurable amount of 2,5-dichlorophenol in urine does not imply that the level of the 2,5-dichlorophenol will result in an adverse health effect. Biomonitoring studies of 2,5-dichlorophenol will provide physicians and public health officials with reference values so that they can determine whether other people have been exposed to higher levels of 2,5-dichlorophenol than levels found in the general population. Biomonitoring data can also help scientists plan and conduct research on exposure and health effects.
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