Biomonitoring Summary

ortho-Phenylphenol

CAS No. 90-43-7

General Information

Ortho-phenylphenol (OPP, or 2-phenylphenol) and its water-soluble salt, sodium ortho-phenylphenate (SOPP), are antimicrobial agents used as bacteriostats, fungicides, and sanitizers. Both have been used in agriculture to control fungal and bacterial growth on stored crops, such as fruits and vegetables. SOPP is applied topically to the crop and then rinsed off, leaving the chemical residue, OPP. Most agricultural food applications have been revoked, but OPP and SOPP are still used on pears and citrus (U.S.EPA, 2006). OPP is still used as a disinfectant fungicide for industrial applications, on ornamental plants and turfs, in paints, and as a wood preservative. In the past, it was used in home sanitizers for surfaces. OPP is volatile and has limited water solubility, whereas SOPP is not volatile and is more water soluble. Both chemicals degrade within hours to weeks in the environment (U.S. EPA, 2006).

General population exposure can occur via dermal, inhalational, or oral routes from residential use and by ingesting treated food or food that was in contact with treated surfaces or equipment. OPP was detected in 40 of 60 different canned beers at concentrations in the low parts per billion (Coelhan et al., 2006). Estimated human intakes have been below recommended intake limits (U.S.EPA, 2006). Workers who manufacture, formulate, or apply these chemicals may be more highly exposed than the general population. OPP is efficiently absorbed from the gastrointestinal tract and through the skin, and is eliminated rapidly from the body as OPP glucuronide and sulfate conjugates (Bartels et al., 1998; Cnubben et al. 2002; Timchalk et al., 1998). Available evidence suggests that OPP does not accumulate in the body; however, small amounts of OPP have been measured in human adipose tissue (Onstot and Stanley, 1989).

Human health effects from OPP at low environmental doses or at biomonitored levels from low environmental exposures are unknown. OPP is considered to be moderately toxic after acute oral doses in animal studies. Chronic dosing in animals resulted in systemic effects such as weight loss and anemia, but no neurologic, reproductive, or developmental toxicity (Bomhard et al., 2002; U.S.EPA 2006). OPP was not mutagenic. Dermally-applied OPP was not carcinogenic in a 2-year experimental in animals (NTP, 1986). In high dose animal studies, OPP or SOPP produced carcinomas of the bladder only after phase II detoxification pathways were saturated, leading to production of two metabolites, ortho-phenylhydroquinone or ortho-phenylbenzoquinone. These metabolites may induce carcinogenicity via nongenotoxic regenerative hyperplasia of the bladder (Appel, 2000; Bomhard et al., 2002; Brusick, 2005; Kwok et al., 1999; Nakagawa et al., 1992; Smith et al., 1998; U.S.EPA 2006), or, less likely, by possible genotoxic mechanisms (Hagiwara et al., 1984; Ito et al., 1984; Murata et al., 1999; Pathak and Roy, 1993; Zhao et al., 2002). IARC has classified SOPP as a possible human carcinogen and OPP as not classifiable as a human carcinogen. Additional information is available from U.S.EPA at: https://www.epa.gov/pesticides/.

Biomonitoring Information

Urinary OPP levels reflect recent exposure. Detectable levels were seen in less than half the U.S. population in the subsamples from NHANES 2005-2006, 2007-2008, and 2009-2010 (CDC, 2012). Volunteers exposed to 0.4 mg dermally had urinary levels of OPP that were several hundred times higher than median levels found in NHANES 2003-2004 (Bartels et al., 1997; CDC, 2012).

Finding a measurable amount of OPP in urine does not imply that the level of OPP causes an adverse health effect. Biomonitoring studies on levels of OPP provide physicians and public health officials with reference values so that they can determine whether people have been exposed to higher levels of OPP than are found in the general population. Biomonitoring data can also help scientists plan and conduct research on exposure and health effects.

References

Appel KE. The carcinogenicity of the biocide ortho-phenylphenol. Arch Toxicol 2000;74(2):61-71.

Brusick D. Analysis of genotoxicity and the carcinogenic mode of action for ortho-phenylphenol. Environ Mol Mutagen 2005;45(5):460-81.

Bartels MJ, Brzak KA, Bormett GA. Determination of ortho-phenylphenol in human urine by gas chromatography-mass spectrometry. J Chromatogr B Biomed Sci Appl 1997;703(1-2):97-104.

Bartels MJ, McNett DA, Timchalk C, Mendrala AL, Christenson WR, Sangha GK, Brzak KA, Shabrang SN. Comparative metabolism of ortho-phenylphenol in mouse, rat and man. Xenobiotica 1998;28(6):579-94.

Bomhard EM, Brendler-Schwaab SY, Freyberger A, Herbold BA, Leser KH, Richter M. O-phenylphenol and its sodium and potassium salts: a toxicological assessment. Crit Rev Toxicol 2002;32(6):551-625.

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

Cnubben NH, Elliott GR, Hakkert BC, Meuling WJ, van de Sandt JJ. Comparative in vitro-in vivo percutaneous penetration of the fungicide ortho-phenylphenol. Regul Toxicol Pharmacol 2002;35(2 Pt 1):198-208.

Coelhan M, Bromig KH, Glas K, Roberts AL. Determination and levels of the biocide ortho-phenylphenol in canned beers from different countries. J Agric Food Chem 2006;54(16):5731-5.

Hagiwara A, Shibata M, Hirose M, Fukushima S, Ito N. Long-term toxicity and carcinogenicity study of sodium o-phenylphenate in B6C3F1 mice. Food Chem Toxicol 1984;22(10):809-14.

Ito N, Fukushima S, Shirai T, Hagiwara A, Imaida K. Drugs, food additives and natural products as promoters in rat urinary bladder carcinogenesis. IARC Sci Publ 1984;(56):399-407.

Kwok ES, Buchholz BA, Vogel JS, Turteltaub KW, Eastmond DA. Dose-dependent binding of ortho-phenylphenol to protein but not DNA in the urinary bladder of male F344 rats. Toxicol Appl Pharmacol 1999;159(1):18-24.

Murata M, Moriya K, Inoue S, Kawanishi S. Oxidative damage to cellular and isolated DNA by metabolites of a fungicide ortho-phenylphenol. Carcinogenesis 1999;20(5):851-7.

Nakagawa Y, Tayama S, Moore GA, Moldeus P. Relationship between metabolism and cytotoxicity of ortho-phenylphenol in isolated rat hepatocytes. Biochem Pharmacol 1992;43(7):1431-7.

National Toxicology Program (NTP). NTP Technical report on the toxicology and carcinogenesis studies of ortho-phenylphenol (CAS No. 90-43-7) in Swiss CD-1 mice (dermal studies). March 1986. Available at URL: https://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr301.pdf. 1/10/13

Onstot JD, Stanley JS. Identification of SARA compounds in adipose tissue. U.S. Environmental Protection Agency (U.S. EPA), Office of Toxic Substances; 1989. EPA-560/5-89-003.

Pathak DN, Roy D. In vivo genotoxicity of sodium ortho-phenylphenol: phenylbenzoquinone is one of the DNA-binding metabolite(s) of sodium ortho-phenylphenol. Mutat Res 1993;286(2):309-19.

Smith RA, Christenson WR, Bartels MJ, Arnold LL, St John MK, Cano M, et al. Urinary physiologic and chemical metabolic effects on the urothelial cytotoxicity and potential DNA adducts of o-phenylphenol in male rats. Toxicol Appl Pharmacol 1998;150(2):402-413.

Timchalk C, Selim S, Sangha G, Bartels MJ. The pharmacokinetics and metabolism of 14C/13C-labeled ortho-phenylphenol formation following dermal application to human volunteers. Hum Exp Toxicol 1998;17(8):411-7.

U.S. Environmental Protection Agency (U.S.EPA). Reregistration Eligibility Decision (RED) for 2-phenylphenol and salts (Orthophenylphenol or OPP). July 28, 2006. EPA 739 R-06-004. Available at URL: https://www.epa.gov/oppsrrd1/REDs/phenylphenol_red.pdf. 1/10/13

Zhao S, Narang A, Gierthy J, Eadon G. Detection and characterization of DNA adducts formed from metabolites of the fungicide ortho-phenylphenol. J Agric Food Chem 2002;50(11):3351-8.