Parabens possess estrogenic effects (10). And the longer paraben

Parabens Parabens, the alkyl esters of p- hydroxybenzoic
acids (PHBA) (68), are a group of non- persistent chemicals (74) used
individually or in mixtures to reach preferred antimicrobial- and preservative
effects. They are especially effective against molds and yeasts, and are widely
(18) used because of their antimicrobial-, and relatively non- irritating- and
non- sensitizing properties. Parabens have low acute toxicity (9, 68, 77), but
have been associated with allergy. They also have low cost, (9) and are
pH-stable (i.e. they help in preventing too rapid product degradation) (68,
77). Short chained parabens are more hydrophilic and the long chained are more
lipophilic (figure 5). When the chain length of the paraben increases, the
resistance to hydrolysis and antimicrobial activity increase (9), but water
solubility decrease. As a consequence, methylparaben (MP) and propylparaben
(PP), which have shorter chains, are the ones most used in cosmetics (9). MP
and PP are however also preferred for use in foods (68, 77). MP, PP,
butylparaben (BP), ethylparaben (EP), heptyl- (HP) and benzylparaben (BzP), isopropyl-
and isobutylparaben are homologous (30, 68, 77). The use of parabens have
caused concern due to their possession of estrogenic- (9) and antiandrogenic
properties (65, 66) (i.e. they can act as ER agonists and AR antagonists).
Parabens may affect health at lower concentrations and more precise than non-
receptor mediated mechanisms, because of their capability binding to ERs (69).
Several studies, both in vitro and in vivo, have demonstrated parabens
disruptive effects in physiologically important mechanisms. The disruptive
effect most described in research, is the parabens ability to bind to human
ERs, and 28 thereafter regulate gene expression and cell growth in estrogen-
responsive cells through ER mediated mechanisms (figure 6). But parabens do
also have the potential to antagonize AR– mediated effects in androgen-
responsive cells, and to behave as sulfotransferase enzyme (SULTs) inhibitors
(10) and act on the regulation of steroids (61). In fact, both in vitro and in
vivo assays show all common native parabens possess estrogenic effects (10).
And the longer paraben chain, from MP to n- BP, the larger are these effects
(9, 78). A higher estrogenic effect is also associated with branching in the
alkyl chain, from n- PP to isopropylparaben (79), and n- BP to isobutylparaben
(80). However, the estrogenic effects have been detected to be 10 000 to 100
000- fold weaker than natural 17?- estradiol, after subcutaneous administration
to rats (78). According to Darbre et al. (80), isobutylparaben has the strongest
estrogenic effect. PHBA, parabens main metabolite, have a weaker estrogenic
effect than native parabens (10). Despite unclear estrogenicity of glycine-,
sulfate- and glucuronide conjugates, the Scientific Committee on Consumer
Safety (SCCS) (81) has concluded that they are most likely not estrogenic. This
conclusion was mainly based on the fact that steroid conjugates themselves
cause no effect at the receptor (81). In theory, as a consequence of parabens
estrogenic- and antiandrogenic effects, parabens may cause diseases related to
the endocrine system. Reproductive diseases and endocrine cancers have been of
special concern. For instance, parabens have been detected in larger
concentrations in the axilla area compared to the lateral, mid and medial side
of the breast, and a link between parabens in underarm cosmetics and breast
cancer has been suggested (82). No association, however, has been made between
single parabens and breast cancer. A recent study by Charles and Darbre (83) on
the other hand, showed that combinations of parabens in human breast tissues
are large enough to stimulate proliferation of MCF- 7 breast cancer cells. In
some tissue samples, all single parabens measured were detected at
concentrations below “no- observedeffect- concentration” (NOEC) (83). This
shows the importance to also consider mixtures of EDCs

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