Biomonitoring Summary

Phthalates Overview

Di-isobutyl Phthalate

CAS No. 84-69-5

General Information

Dibutyl phthalates (both di-n-butyl and di-isobutyl phthalates, referred to as DBP) are industrial solvents or additives used in many personal care products such as nail polish and cosmetics, and also in some printing inks, pharmaceutical coatings, and insecticides. People exposed to dibutyl phthalates will excrete mono-n-butyl phthalate (MnBP) and mono-isobutyl phthalate (MiBP) in their urine. When total DBP metabolites have been measured, they have been referred to as monobutyl phthalate (MBP). Small amounts of mono-3-carboxypropyl phthalate are also produced from di-n-butyl phthalate. In addition, exposure to benzylbutyl phthalate (BzBP) will also result in small amounts of mono-n-butyl phthalate appearing in the urine. Following oral administration of DBP to humans, about 65% to 80% of a dose is eliminated in urine within 24 hours, mostly as MnBP (Anderson et al., 2001). DBP can produce reproductive toxicity in male rodents (McKee et al., 2004; NTP-CERHR, 2000). OSHA has established a workplace air standard for external exposure to DBP; NIOSH and ACGIH have established guidelines for workplace air exposure to di-n-butyl phthalate. Neither IARC nor NTP has evaluated dibutyl phthalates with respect to human carcinogenicity.

Biomonitoring Information

Median concentrations reported in the NHANES 1999-2000, 2001-2002 and 2003-2004 subsamples were similar to MBP levels reported in U.S. residents (Blount et al., 2000), in men attending a Boston infertility clinic (Duty et al., 2004; Hauser et al., 2007), in a small sample of pregnant women in New York City (Adibi et al., 2003), and in a small sample of Japanese adults (Itoh et al., 2005). Median MBP levels in two European studies were about two to six times higher than median levels in the National Report on Human Exposure to Environmental Chemicals (CDC, 2013; Jonsson et al., 2005; Koch et al., 2003). Studies of children found age-related differences in urine MBP levels. Compared with the median for 6 to 11 year olds in NHANES 1999-2004 (CDC, 2013), the median for neonates was lower (by about half) and the median for toddlers was higher (by about sixfold) (Brock et al., 2002; Weuve et al., 2006). In an analysis of NHANES 1999-2000, the adjusted geometric mean levels of urinary MBP were significantly higher in children aged 6 to 11 years than in either adolescents or adults (Silva et al., 2004). Differences in urinary MBP population estimates by gender have also been shown (Silva et al., 2004). An analysis of NHANES 2001-2002 showed similar age- and gender- related differences in the adjusted geometric mean levels of urinary MiBP and MnBP (CDC, 2013).

Studies measuring urinary MnBP have reported variable median values compared to the NHANES 2001-2002 and 2003-2004 subsamples, ranging from more than one-tenth the NHANES median (Itoh et al, 2005), to about two to fourfold higher (Fromme et al., 2007). Between 1998 and 2003, samples from German university students had consistently higher median urine levels of MnBP and MiBP, up to four and 13 fold, respectively, than adults in NHANES subsamples during the same time period (CDC, 2012). Over this time, the students’ median values for MiBP levels remained relatively unchanged, while MnBP declined (Wittassek et al., 2007).

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


Adibi JJ, Perera FP, Jedrychowski W, Camann DE, Barr D, Jacek R, et al. Prenatal exposures to phthalates among women in New York City and Krakow, Poland. Environ Health Perspect 2003;111(14):1719-1722.

Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological profile for di-n-butyl phthalate update [online]. September 2001. Available at URL: 6/21/13

Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological profile for di(2-ethylhexyl)phthalate update [online]. September 2002. Available at URL: 6/21/13

Albro PW, Corbett JT, Schroeder JL, Jordan S, Matthews HB. Pharmacokinetics, interactions with macromolecules and species differences in metabolism of DEHP. Environ Health Perspect 1982;45:19-25.

Albro PW and Lavenhar SR. Metabolism of di(2-ethylhexyl) phthalate. Drug Metab Rev 1989;21:13-34.

Anderson WA, Castle L, Scotter MJ, Massey RC, Springall C. A biomarker approach to measuring human dietary exposure to certain phthalate diesters. Food Addit Contam 2001;18(12):1068-1074.

Blount BC, Silva MJ, Caudill SP, Needham LL, Pirkle JL, Sampson EJ, et al. Levels of seven urinary phthalate metabolites in a human reference population. Environ Health Perspect 2000;108(10)979-982.

Brock JW, Caudill SP, Silva MJ, Needham LL, Hilborn ED. Phthalate monoesters levels in the urine of young children. Bull Environ Contam Toxicol 2002;68:309-314.

Calafat AM, Slakman AR, Silva MJ, Herbert AR, Needham LL. Automated solid phase extraction and quantitative analysis of human milk for 13 phthalate metabolites. J Chromatogr B 2004;805:49-56.

Centers for Disease Control and Prevention (CDC). Fourth National Report on Human Exposure to Environmental Chemicals. Updated Tables, 2013. [online] Available at URL: 6/21/13

Clark K, Cousins IT, Mackay D. Assessment of critical exposure pathways. In Staples CA (ed), The Handbook of Environmental Chemistry, Vol, 3, Part Q: Phthalate Esters. 2003;New York, Springer, pp. 227-262.

Coldham NG, Dave M, Silvapathasundaram S, McDonnell DP, Connor C, Sauer MJ. Evaluation of a recombinant yeast cell estrogen screening assay. Environ Health Perspect 1997; 105:734-742.

Dirven HA, van der Broek PH, Jongeneelen FJ. Determination of four metabolites of the plasticizer di (2-ethylhexyl) phthalate in human urine samples. Int Arch Occup Environ Health 1993;64(8):555-560.

Duty SM, Calafat AM, Silva MJ, Brock JW, Ryan L, Chen Z, et al. The relationship between environmental exposure to phthalates and computer-aided sperm analysis motion parameters. J Androl 2004;25(2):293-302.

Fromme H, Bolte G, Koch HM, Angerer J, Boehmer S, Drexler H, et al. Occurrence and daily variation of phthalate metabolites in the urine of an adult population. Int J Hyg Environ Health 2007;210:21-33.

Harris CA, Henttu P, Park MG, Sumpter JP. The estrogenic activity of phthalate esters in vitro. Environ Health Perspect 1997;105:802-811.

Hauser R, Meeker JD, Park S, Silva MJ, Calafat AM. Temporal variability of urinary phthalate metabolite levels in men of reproductive age [published erratum appears in Environ Health Perspect 2004;112(17):1740]. Environ Health Perspect 2004;112(17):1734-1740.

Hauser R, Meeker JD, Singh NP, Silva MJ, Ryan L, Duty S, et al. DNA damage in human sperm is related to urinary levels of phthalate monoester and oxidative metabolites. Hum Reprod 2007;22(3):688-695.

Hoppin JA, Brock JW, Davis BJ, Baird DD. Reproducibility of urinary phthalate metabolites in first morning urine samples. Environ Health Perspect 2002;110(5):515-518.

Itoh H, Yoshida K, Masunaga S. Evaluation of the effect of governmental control of human exposure to two phthalates in Japan using a urinary biomarker approach. Int J Hyg Environ Health 2005;208:237-245.

Jarfelt K, Dalgaard M, Hass U, Borch J, Jacobsen H, Ladefoged O. Antiandrogenic effects in male rats perinatally exposed to a mixture of di(2-ethylhexyl) phthalate and di(2-ethylhexyl) adipate. Reprod Toxicol 2005;19(4):505-515.

Jobling S, Reynolds T, White R, Parker MG, Sumpter JP. A variety of environmentally persistent chemicals including some phthalate plasticizers are weakly estrogenic. Environ Health Perspect 1995;103:582-587.

Jonsson BAG, Richthoff J, Rylander L, Giwercman A, Hagmar L. Urinary phthalate metabolites and biomarkers of reproductive function in young men. Epidemiol 2005;16(4):487-493.

Kessler W, Numtip W, Grote K, Csanády G, Chahoud I, Filser J. Blood burden of di(2-ethylhexylphthalate (DEHP) and its primary metabolite mono(2-ethylhexyl) phthalate (MEHP) in pregnant and non-pregnant rats and marmosets. Toxicol Appl Pharmacol 2004;195:142-153.

Koch HM, Rossbach B, Drexler H, Angerer J. Internal exposure of the general population to DEHP and other phthalates – determination of secondary and primary phthalate monoester metabolites in urine. Environ Res 2003;93:177-185.

Liss GM, Albro PW, Hartle RW, Stringer WT. Urine phthalate determinations as an index of occupational exposure to phthalic anhydride and di (2-ethylhexyl) phthalate. Scand J Work Environ Health 1985;11(5):381-387.

Lovekamp-Swan T, Davis BJ. Mechanisms of phthalate ester toxicity in the female reproductive system. Environ Health Perspect 2003;111(2):139-145.

McKee RH, Butala JH, David RM, Gans G. NTP center for the evaluation of risks to human reproduction reports on phthalates: addressing the data gaps [review]. Reprod Toxicol 2004;18(1):1-22.

Milligan SR, Balasubramanian AV, Kalita JC. Relative potency of xenobiotic estrogens in an acute in vivo mammalian assay. Environ Health Perspect 1998;106(1):23-26.

Mortensen GK, Main KM, Andersson A-M, Leffers H, Skakkebaek NE. Determination of phthalate monoesters in human milk, consumer milk, and infant formula by tandem mass spectrometry (LC-MS-MS). Anal Bioanal Chem 2005;382:1084-1092.

Nielsen J, Akesson B, Skerfving S. Phthalate ester exposure—air levels and health of workers processing polyvinylchloride. Am Ind Hyg Assoc J 1985;46(11):643-647.

NTP-CERHR. National Toxicology Program-Health Assessment and Translation (formerly CERHR). Monograph on the Potential Human Reproductive and Developmental Effects of Butyl Benzyl Phthalate (BBP). Research Triangle Park (NC). 2003a [online]. Available at URL: iconexternal icon. 6/21/13

NTP-CERHR. National Toxicology Program-Health Assessment and Translation (formerly CERHR). Monograph on the Potential Human Reproductive and Developmental Effects of Di-n-Butyl Phthalate (DBP). Research Triangle Park (NC). 2003b [online]. Available at URL: iconexternal icon.6/21/13

NTP-CERHR. National Toxicology Program-Health Assessment and Translation (formerly CERHR). Monograph on the Potential Human Reproductive and Developmental Effects of Di(2-ethylhexyl) Phthalate (DEHP). Research Triangle Park (NC). 2006 [online]. Available at URL: iconexternal icon. 6/21/13

Okubo T, Suzuki T, Yokoyama Y, Kano K, Kano I. Estimation of estrogenic and anti-estrogenic activities of some phthalate diesters and monoesters by MCF-7 cell proliferation assay in vitro. Biol Pharm Bull 2003;26(8):1219-24.

Pan G, Hanaoka T, Yoshimura M, Zhang S, Wang P, Tsukino H, et al. Decreased serum free testosterone in workers exposed to high levels of di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP): a cross-sectional study in China. Environ Health Perspect 2006;114(11):1643-1648.

Parks LG, Ostby JS, Lambright CR, Abbott BD, Klinefelter GR, Barlow NJ, et al. The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal testosterone synthesis during sexual differentiation in the male rat. Toxicol Sci 2000;58:339-349.

Peck CC, Albro PW. Toxic potential of the plasticizer di (2-ethylhexyl) phthalate in the context of its disposition and metabolism in primates and man. Environ Health Perspect 1982;45:11-17.

Rhodes C, Orton TC, Pratt IA, Batten PL, Bratt H, Jackson SJ, et al. Comparative pharmacokinetics and subacute toxicity of di(2-ethylhexyl)phthalate (DEHP) in rats and marmosets: Extrapolation of effects in rodents to man. Environ Health Perspect 1986;65:299-308.

Rusyn I, Peters JM, Cunningham ML. Modes of action and species-specific effects of di-(2-ethylhexyl) phthalate in the liver. Crit Rev Toxicol 2006;36:459-479.

Silva MJ, Barr DB, Reidy JA, Malek NA, Hodge CC, Caudill SP, et al. Urinary levels of seven phthalate metabolites in the U.S. population from the National Health and Nutrition Examination Survey (NHANES) 1999-2000 [published erratum appears in Environ Health Perspect 2004; 112(5):A270]. Environ Health Perspect 2004;112(3):331-338.

Weuve J, Sanchez GN, Calafat AM, Schettler T, Green RA, Hu H, et al. Exposure to phthalates in neonatal intensive care unit infants: urinary concentrations of monoesters and oxidative metabolites. Environ Health Perspect 2006;114(9):1424-1431.

Wittassek M, Wiesmuller GA, Koch HM, Eckard R, Dobler L, Helm D, et al. Internal phthalate exposure over the last two decades—a retrospective human biomonitoring study. Int J Hyg Environ Health 2007;210(3-4):319-333.

Zacharewski TR, Meek MD, Clemons JH, Wu ZF, Fielden MR, Matthews JB. Examination of the in vitro and in vivo estrogenic activities of eight commercial phthalate esters. Toxicol Sci 1998;46:282-293.

Page last reviewed: April 7, 2017