Biomonitoring Summary

2,5-Dichlorophenol

CAS No. 583-78-8
Metabolite of 1,4-Dichlorobenzene (Paradichlorobenzene)

General Information

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.

Biomonitoring Information

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.

References

Becker K, Schulz C, Kaus S, Seiwert M, Seifert B. German environmental survey 1998 (GerES III): environmental pollutants in the urine of the German population. Int J Hyg Environ Health 2003;206:15-24.

Castorina R, Bradman A, Fenster L, Barr DB, Bravo R, Vedar MG, et al. Comparison of current-use pesticide and other toxicant urinary metabolite levels among pregnant women in the CHAMACOS cohort and NHANES. Environ Health Perspect 2010;118(6):856-63.

Centers for Disease Control and Prevention (CDC). Fourth National Report on Human Exposure to Environmental Chemicals. Updated Tables, September 2012. [online] Available at URL: https://www.cdc.gov/exposurereport/. 12/28/12

Cotter LH. Paradichlorobenzene poisoning from insecticides. NY State J Med 1953;53:1690-2.

Dodson RE, Houseman EA, Levy JI, Spengler JD, Shine JP, Bennett DH. Measured and modeled personal exposures to and risks from volatile organic compounds. Environ Sci Technol 2007;41:8498-505.

Hazardous Substances Data Bank (HSDB). 2,5-dichlorophenol. National Library of Medicine, Bethesda, MD: National Institutes of Health; Updated 8/20/2009. Available at URL:

https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB. 1/4/13

Hill RH Jr, Ashley DL, Head SL, Needham LL, Pirkle JL. P-dichlorobenzene exposure among 1000 adults in the United Sates. Arch Environ Health 1995a;50(4):227-80.

Hill RH Jr, Head SL, Baker S, Gregg M, Shealy DB, Bailey SL, et al. Pesticide residues in urine of adults living in the United States: reference range concentrations. Environ Res 1995b;71:99-108.

Hill RH Jr, To T, Holler JS, Fast DM, Smith J, Needham LL, et al. Residues of chlorinated phenols and phenoxy acid herbicides in the urine of Arkansas children. Arch Environ Contam Toxicol 1989;18:469-74.

Hissink AM. Dunnewijk R, van Ommen B, van Bladeren PJ. Kinetics and metabolism of 1,4-dichlorobenzene in male Wistar rats: no evidence for quinine metabolites. Chem Biol Interact 1997;103(1):17-33.

Hsiao PK, Lin YC, Shih TS, Chiung YM. Effects of occupational exposure to 1,4-dichlorobenzene on hematologic, kidney, and liver function. Int Arch Occup Environ Health 2009;82:1077-85.

International Agency for Research on Cancer (IARC). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol. 73, 1999. Some chemicals that cause tumours of the kidney or urinary bladder in rodents and some other substances. Available at: http://monographs.iarc.fr/ENG/Monographs/vol73/mono73-13.pdf. 10/15/12

National Toxicology Program (NTP). Report on Carcinogens, Twelfth Edition (2011); U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Website updated May 08, 2012. Available at URL: https://ntp.niehs.nih.gov/ntp/roc/twelfth/profiles/Dichlorobenzene.pdf 10/15/12

Pagnotto LD, Walkley JE. Urinary dichlorophenol as an index of para-dichlorobenzene exposure. Ind Hyg J 1965; 26:137-42.

Saijo Y, Kishi R, Sata F, Katakura Y, Urashima Y, Hatakeyama A, et al. Symptoms in relation to chemicals and dampness in newly build dwellings. Int Arch Occup Environ Health 2004;77:461-70.

Tegethoff TK, Herbold BA, Bomhand EM. Investigations on the mutagenicity of 1,4-dichlorobenzene and its main metabolite 2,5-dichlorophenol in vivo and in vitro. Mutat Res 2000;470(2):161-7.

Wallace LA, Pellizzarri ED, Hartwell TD, Sparacino C, Whitmore R, Sheldon L, et al. The TEAM study: personal exposures to toxic substances in air, drinking water, and breath of 400 residents of New Jersey, North Carolina and North Dakota. Environ Res 1987;43:290-307.

Yoshida T, Andoh K, Fukuhara M. Urinary 2,5-dichlorophenol as biological index for p-dichlorobenzene exposure in the general population. Arch Environ Contam Toxicol 2002;43:481-5.