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Advisory Committee on Health Effects of Endocrine Disruptors
The Supplement II to the Intermediary Report
1.3.2 |
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Effects on the protective immunity are still poorly understood,
as seen in Global Assessment. Studies of (1) in vivo33
effects of DES on adult mice34,
(2) effects of DES, estradiol, BPA, p-n-octylphenol, and
benzyl-n-butyl phthalate on the multiplication and
differentiation of T cells by fetal thymic organ culture 35,
and (3) effects of the same compounds on the multiplication of
splenic T cells, indicate that these compounds tend to retard
the early multiplication and differentiation of T cells.
Administering 2.5 or 10.0 Κg.ml BPA via feed water to pregnant
mice resulted seemingly in a delayed development of the immune
system36. Nonylphenol (NP),
BPA, butylbenzyl phthalate (BBP) and dibutyl phthalate (DBP)
were observed to affect, even at low doses, the production of
cytokines (IL-2, IL-10, IFN-Α, etc.) in B cells by mitogens. In
particular BPA led to increase in calcium ion concentration in
cells, concomitantly with tyrosine phosphorylation in proteins37.
Expression of ERΏ and ERΐ in the nerve system has been reported.
Their subsequent differentiation and self-replication capacity
was found to decrease after exposure to DES in an unpublished
work. Expression of orphan receptors RVR and TR4 was observed in
precursor cells, but the biological background of this
observation is not clear. Neuroendocrinologic studies of effects
on sex differentiation are in progress, but correlation with the
dose is not yet established38.
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33 Experiments on the
level of individual organisms.
34 Utsuyama M, Kanno J, Inoue T,
Hirokawa K. Age/sex dependent and non-monotonous dose-response
effect of diethylstilbestrol on the immune functions in mice.
Toxicol Lett. 135: 145-153, 2002.
35 As for the function of the T cell
system, the differentiation and multiplication of fetal thymic
cells (CD44+CD25-) to subpopulations (CD44+CD25-) was reportedly
retarded by DES or BPA at levels as low as 0.01-1 nM.
36 Unpublished new data.
37 Yamazaki T, Ezaki O. Effect of endocrine disruptors on
lymphocyte responses. Organohalogen Compounds. 56: 107-110,
2002. / Yamazaki T, Okada Y, Hisamatsu Y, Kubota S, Kayama F.
Effects of endocrine disrupting chemicals on lymphocyte
responses. Organohalogen Compounds. 49: 394-396, 2000.
38 Study of interactions of GnRH1
and GnRH3 with PXR and RXR using the total RNA obtained from
GnRH neurons identified by laser capture suggested that GnRH1
and GnRH3 are regulated by PXR, and sex differentiation of the
genital primordium and sexual behavior are controlled by GnRH1
and GnRH3, respectively. However, data on the dose needed for
the expression are not obtained (Palhar IS. Gonadotropin-releasing
hormone receptors: neuroendocrine regulators and neuromodulators.
Fish Physiol. Biochem. in press). |
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