Front Matter

192 Autism and Exposure to Environmental Chemicals

plastic and can readily leach into the environment. Furthermore, a large

number of consumer products use various phthalates, and in fact, phthalate

contamination has been found in a large variety of foods, including sports

drinks, fruit beverages, tea drinks, fruit jam or jelly, and health foods or supple­

ments in powder or tablet form, ice cream, frozen food, and cake mixes [77].

Phthalates are detectable in human urine, serum, and breast milk [78–80], and

the estimated daily exposure to one major phthalate, di(2‐ethylhexyl) phthalate

(DEHP), ranges from 3 to 30 μg/kg/day [81].

When metabolized by the liver, DEP is a phthalate ester and is a solvent

for many organic compounds. It is most commonly found in fragrance, cos­

metics, and perfumes. Numerous well‐documented studies suggest that

DEP can cause damage to the nervous system as well as to the reproductive

organs in males and females [82–84]. DEP is reduced and excreted in the

urine as monoethyl phthalate (MEP; Figure  7.6). DEP is hydrolyzed to the

monoester, monoethyl phthalate, and ethanol after oral administration in

the lumen of the gastrointestinal tract or in the intestinal mucosal cells.

Hydrolysis of DEP also takes place in the kidney and liver after systemic

absorption. After tissue distribution throughout the body, DEP accumulates

in the liver and kidney. The metabolites are excreted in the urine. DEP is

metabolized by carboxyl esterase, which is synthesized in the human liver.

In vitro studies show that DEP reduces the glucuronyl transferase activity. It

was also observed that the activity of peroxisomal enzyme carnitine acetyl

transferase is increased in cultures of rat liver cells [82–84]. Furthermore,

DEP induces the enzyme activity of catalase, which leads to hepatic peroxi­

some proliferation and possibly causes hyperplasia. Teratogenic effects of

DEP have also been reported [85].

O

OR

OR

O

O

OH

OR

O

O

OH

OR

O O

O

OH

OR

O OH

O

O

O OH

OH

OROH

O

Phase I

R group

hydroxylation

Biotransformation

Diester phthalate Monoester phthalate Phthalate glucuronide

COOH

Phase II

Phase II

Phase II

R group

oxylation

Biotransformation

Figure 7.6 Metabolic pathways of phthalates.