| Abstract |
The advancement and evolution of industry have been closely associated with widespread
pollution and the presence of various chemicals in both the environment and the food chain.
Several surveys have indicated that numerous chemicals possess the capability to disrupt the
endocrine system, and these substances are referred to as endocrine disruptors (EDCs). There
is an increasing body of evidence highlighting their adverse effects on living organisms, which
come into contact with EDCs primarily through the consumption of contaminated food and
fluids, inhalation or absorption through the skin.
Studies on human biomonitoring have revealed that the general population, including children,
is seldom exposed to a solitary compound. Instead, exposure predominantly occurs to chemical
combinations found in the environment (water, air, soil), as well as in food or consumer
products. Currently, there is limited data regarding potential adverse effects both in humans and
animals.
The aim of this PhD thesis was to simulate human exposure to endocrine disruptors in real life.
Specifically, we focused on assessing the synergistic or non-synergistic effects of glyphosate,
BPA, PBs, TCS and DEHP, on the rabbit organism after a 12-month combined exposure to
these compounds. In addition, a comparison was made of the effects following 12 months
exposure to the pure form of glyphosate versus its commercial form (Roundup® herbicide).
The toxicity of the above was assessed by examining redox biomarkers and biological markers
of DNA damage (micronuclei count and comet intensity), and also by measuring reproductive
hormones and estimating cytological damage.
Throughout the in vivo experiment, results from different samplings showed an increase in
micronuclei formation in a dose – and time – dependent manner. The same trend was also
observed for tail intensity, but this was exclusively dose – related, given the limited number of
samples (specifically, only the latter). The group receiving a high dose of a mixture of
substances (HD group) seemed to be more affected in terms of tail intensity, probably due to
the synergistic effect of the administered substances. In all exposure groups, there was a positive
correlation between the number of micronuclei and tail intensity. Administration of the EDCs mixture induced perturbations of blood redox homeostasis at 3
months, while at 6 and 12 months it triggered redox adaptations. In contrast, exposure to GLY
and Roundup®, individually, mainly induced perturbations of blood redox balance. At the
tissue level, especially in the liver, administration of both EDCs mixture and Roundup®
induced oxidative stress, whereas GLY did not. Furthermore, the administration of both EDCs
and Roundup® caused detrimental effects on the redox status of the liver, a critical tissue with
a valuable biological role in the detoxification of organisms from xenobiotics.
According to the results of the measurement of reproductive hormone levels, the female rabbits
did not show any particular differences, except for the case of T4 where both female and male
rabbits showed an increase from 3 months onwards in the HD and Roundup groups. Β-estradiol
remained almost unaffected throughout the experiment with no differences between males and
females. Regarding testosterone levels in male rabbits, they increased after 3 months of
exposure and decreased sharply at 12 months of exposure in the Glyphosate, HD and Roundup
groups. T3 concentration increased at 3 months of exposure onwards and decreased at 12
months of exposure in the Roundup group. In parallel, progesterone levels decreased at 12
months of exposure (compared to 0 months) in the LD, HD and Roundup groups, while they
increased in the Glyphosate group.
The cytological findings make clear the existence of extensive lesions in the HD, Glyphosate
and Roundup groups. Existence of ectasia, degeneration and carcinogenesis were recorded in
liver, kidney, testis, ovary and thyroid gland, while the heart did not show any cytological
lesions.
Our findings indicate that exposure to EDCs, individually and in combination, causes adverse
effects on the cytological scale, the DNA, the hormone levels and the redox status of the
organism. This underlines the potential risks associated with daily exposure to these substances
and highlights the urgent need for additional research in this area.
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