Haam. Dirven et al., DETERMINATION OF 4 METABOLITES OF THE PLASTICIZER DI(2-ETHYLHEXYL)PHTHALATE IN HUMAN URINE SAMPLES, International archives of occupational and environmental health, 64(8), 1993, pp. 555-560
A method for biological monitoring of exposure to the plasticizer di(2
-ethylhexyl)phthalate (DEHP) is described. In this method the four mai
n metabolites of DEHP [i.e., mono(2-ethylhexyl)phthalate (MEHP), mono(
5-carboxy-2-ethylpentyl)phthalate, mono(2-ethyl-5-oxohexyl)phthalate,
and mono(2-ethyl-5-hydroxyhexyl)phthalate] are determined in urine sam
ples. The procedure includes enzymatic hydrolysis, ether extraction, a
nd derivatization with triethyloxonium tetrafluoroborate. Analysis is
performed by gas chromatography-electron impact mass spectrometry. The
detection limit for all four metabolites is less than 25 mug/l urine.
The coefficient of variation based on duplicate determinations of uri
ne samples of workers occupationally exposed to DEHP was 16% for MEHP
(mean concentration 0.157 mg/l) and 6%-9% for the other three metaboli
tes (mean concentrations 0.130-0.175 mg/l). The method described here
was used to study DEHP metabolism in man. Most persons excrete mono(2-
ethyl-5-oxohexyl)phthalate and mono(2-ethyl-5-hydroxyhexyl)phthalate a
s a (glucuronide) conjugate. Mono(5-carboxy-2-ethylpentyl)phthalate is
mainly excreted in free form, while for MEHP a large interindividual
variation in conjugation status was observed. Of the four metabolites
quantified, 52% are products of a (omega-1)-hydroxylation reaction of
MEHP [i.e., mono(2-ethyl-5-oxohexyl)phthalate and mono(2-ethyl-5-hydro
xyhexyl)phthalate], 22% is the product of a omega-hydroxylation reacti
on of MEHP [i.e., mono(5-carboxy-2-ethylpentyl)phthalate], and 26% is
not oxidized further (i.e., MEHP). A good correlation is obtained when
the amount of MEHP (omega-hydroxylation products is compared with the
amount of MEHP (omega-1)hydroxylation products in urine samples. When
the internal dose of DEHP has to be established we recommend that the
levels of all four metabolites of DEHP be studied in urine samples.