Why Male Gender Bias? 131population to an increasingly diverse set of synthetic chemicals may provide
the basis for this alarming 10‐fold increase in autism in recent years. Many
of these synthetic chemicals, including fragrances, have steroidogenic (male
and female hormone‐like chemicals) activity (reviewed in Ref. [68]).
According to published laboratory and epidemiological studies, undisclosed
chemicals in fragrances, such as those that provide different scents, increase
shelf life, control release of fragrance and improve stability, and have endo-
crine‐disrupting properties [33,44,63–66]. Such endocrine disruptors and
brain network modulators have been associated with increased risk for can-
cer [33,44,63–66,68], adverse effects on developing fetuses [33,44,63–66,68],
and metabolic diseases. For example, chemicals that have been shown to
increase human estrogen receptor expression include octinoxate, oxyben-
zone, benzophenone‐1, benzophenone‐2, benzyl salicylate, benzyl benzoate,
butylphenyl methylpropional, and synthetic musks (galaxolide, tonalide,
and musk ketone). Of these, oxybenzone, benzophenone‐1, galaxolide, and
tonalide also affect androgens, while butylated hydroxytoluene, benzophe-
none‐2, and octinoxate have been linked to thyroid hormone disruption
[33]. Even at very low concentrations, fragrances that contain these chemi-
cals can be mutagenic and carcinogenic [33,44]. Of note, one of the fra-
grance ingredients, acetyl ethyl tetramethyl tetraline (AETT) was used for
22 years in fragrances, colognes, soaps, detergents and cosmetics [53].
However, it was voluntarily discontinued in 1978 after it was linked to
behavioral changes and degeneration of the white matter of the brain includ-
ing “widespread demyelination and scattered axonal degeneration in the
central peripheral nervous systems.” Along with this, the fragrance ingredi-
ent musk ambrette (a fixative recently banned in the European Union but
still allowed in the USA) also has been found to cause degeneration of the
myelin sheath and distal axons. Even if one seriously considers high testos-
terone levels during the early stages of gestation, these data do not explain
why the incidence of ASD is steadily going up, except that synthetic chemi-
cals, behaving like hormones, can reach the fetal blood circulation [68]. We
believe that many synthetic fragrances contain testosterone‐like hormones
(see Chapter 7).
Why Male Gender Bias?
A question that remains is why are female neuronal cells relatively more pro-
tected than their male counterparts? Some investigators propose that the male
bias for ASD may be partially due to under diagnosis of autism in females or
the human female’s ability to mask some of the symptoms of ASD [1,2,66].
Even so, these investigators agree that male bias is observed in ASD and it is
3 times more common than the 4–5 times that is reported in many other studies.
Several hypotheses have been advanced including: (1) epigenetic mechanisms