Exploring the endocrine disrupting potential of lead through benchmark modelling – Study in humans

Javorac, Dragana; Baralić, Katarina; Marić, Đurđica; Mandić‐Rajčević, Stefan; Đukić-Ćosić, Danijela; Bulat, Zorica; Djordjevic, Aleksandra Buha

doi:10.1016/j.envpol.2022.120428

Cited by 15 publications

(4 citation statements)

References 41 publications

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“…In the study, performed in China, that included lead-acid battery workers, the authors derived a BMDL of 13.5 µg Pb/dL for a decrease in red blood cells’ concentration, 10.5 µg Pb/dL for a decrease in hemoglobin levels, based on hematological toxicity, and an even tougher threshold of 6.6 µg Pb/dL for micronuclei or 3.5 µg Pb/dL for telomere length, based on genotoxicity [ 53 ]. Our research group’s recent publication demonstrated a connection between lead and hormones’ action, indicating a positive association between BLLs and serum insulin levels, with derived BMDs 1.49 and 0.74 µg Pb/dL in males and females, respectively [ 54 ]. In our study, the observed internal BMDs (blood lead levels) are lower than the values from epidemiological studies; this strengthens the notion that the blood Pb threshold level might be very low.…”

Section: Discussionmentioning

confidence: 99%

Subacute Exposure to Low Pb Doses Promotes Oxidative Stress in the Kidneys and Copper Disturbances in the Liver of Male Rats

Javorac

Djordjevic

Anđelković

et al. 2023

Toxics

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Recent data indicate that lead (Pb) can induce adverse effects even at low exposure levels. Moreover, the corresponding mechanisms of low Pb toxicity have not been well identified. In the liver and the kidneys, Pb was found to induce various toxic mechanisms leading to organ physiological disruption. Therefore, the purpose of the study was to simulate low-dose Pb exposure in an animal model with the aim of assessing oxidative status and essential element levels as the main mechanism of Pb toxicity in the liver and kidneys. Furthermore, dose–response modelling was performed in order to determine the benchmark dose (BMD). Forty-two male Wistar rats were divided into seven groups: one control group, and six groups treated for 28 days with 0.1, 0.5, 1, 3, 7, and 15 mg Pb/kg b.w./day, respectively. Oxidative status parameters (superoxide dismutase activity (SOD), superoxide anion radical (O2−), malondialdehyde (MDA), total sulfhydryl groups (SHG), and advanced oxidation protein products (AOPP)) and Pb, copper (Cu), zinc (Zn), manganese (Mn), and iron (Fe) levels were measured. Lowering Cu levels (BMD: 2.7 ng/kg b.w./day), raising AOPP levels (BMD: 0.25 µg/kg b.w./day) in the liver, and inhibiting SOD (BMD: 1.3 ng/kg b.w./day) in the kidneys appear to be the main mechanisms of Pb toxicity. The lowest BMD was derived for a decrease in Cu levels in liver, indicating that this effect is the most sensitive.

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Section: Discussionmentioning

confidence: 99%

Subacute Exposure to Low Pb Doses Promotes Oxidative Stress in the Kidneys and Copper Disturbances in the Liver of Male Rats

Javorac

Djordjevic

Anđelković

et al. 2023

Toxics

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“…In a study that examined the dose-response relationship between Cd, arsenic (As), Hg, Ni, and chromium (Cr) in the blood and testosterone, luteinizing, and follicle-stimulating hormones in the serum of men, a dose-response relationship was established for all metal-hormone pairs ( 19 ), and also for metal and testosterone in women, and estradiol and progesterone in men ( 22 ). In a study where the relationship between the exposure to Pb and endocrine function of the organism was monitored, the narrowest BMDI was obtained for the Pb-insulin pair ( 20 ). These studies point to two important conclusions.…”

Section: Discussionmentioning

confidence: 99%

Nickel as a potential disruptor of thyroid function: benchmark modelling of human data

Maric,

Baralic,

Javorac

et al. 2023

Front. Endocrinol.

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IntroductionNickel (Ni) is one of the well-known toxic metals found in the environment. However, its influence on thyroid function is not explored enough. Hence, the aim of this study was to analyse the potential of Ni to disrupt thyroid function by exploring the relationship between blood Ni concentration and serum hormone levels (TSH, T4, T3, fT4 and fT3), as well as the parameters of thyroid homeostasis (SPINA-GT and SPINA-GD) by using correlation analysis and Benchmark (BMD) concept.MethodsNi concentration was measured by ICP-MS method, while CLIA was used for serum hormone determination. SPINA Thyr software was used to calculate SPINA-GT and SPINA-GD parameters. BMD analysis was performed by PROAST software (70.1). The limitations of this study are the small sample size and the uneven distribution of healthy and unhealthy subjects, limited confounding factors, as well as the age of the subjects that could have influenced the obtained results.Results and discussionThe highest median value for blood Ni concentration was observed for the male population and amounted 8,278 µg/L. Accordingly, the statistically significant correlation was observed only in the male population, for Ni-fT4 and Ni-SPINA-GT pairs. The existence of a dose-response relationship was established between Ni and all the measured parameters of thyroid functions in entire population and in both sexes. However, the narrowest BMD intervals were obtained only in men, for Ni - SPINA-GT pair (1.36-60.9 µg/L) and Ni - fT3 pair (0.397-66.8 µg/L), indicating that even 78.68 and 83.25% of men in our study might be in 10% higher risk of Ni-induced SPINA-GT and fT3 alterations, respectively. Due to the relationship established between Ni and the SPINA-GT parameter, it can be concluded that Ni has an influence on the secretory function of the thyroid gland in men. Although the further research is required, these findings suggest possible role of Ni in thyroid function disturbances.

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“…Therefore, the endocrine toxicity of Pb still exists and needs more attention and investigation. Previous studies have primarily investigated the impact of Pb on the endocrine (thyroid hormones and sex hormones), nervous (neurotransmitters/neuropeptides), and immune systems (inflammatory cytokines) [22][23][24][25][26]. Specifically, there are inconsistent epidemiological results in the association between Pb and thyroid hormones [27][28][29].…”

Section: Lead (Pb)mentioning

confidence: 99%

Effects of Endocrine-Disrupting Heavy Metals on Human Health

Liu

Shi

Liu

et al. 2023

Toxics

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Heavy metals play an important endocrine-disrupting role in the health consequences. However, the endocrine-disrupting mechanism of heavy metals is unclear. There are long-term and low-level metal/element exposure scenes for the human body in real life. Therefore, animal models exposed to high doses of heavy metals may not provide key information to elucidate the underlying pathogeny of human diseases. This review collects current knowledge regarding the endocrine-disrupting roles of heavy metals such as lead (Pb), cadmium (Cd), arsenic (As), mercury (Hg), nickel (Ni), copper (Cu), zinc (Zn), and manganese (Mn), summarizes the possible molecular mechanisms of these endocrine-disrupting chemicals (EDCs), and briefly evaluates their endocrine toxicity on animals and humans.

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Exploring the endocrine disrupting potential of lead through benchmark modelling – Study in humans

Cited by 15 publications

References 41 publications

Subacute Exposure to Low Pb Doses Promotes Oxidative Stress in the Kidneys and Copper Disturbances in the Liver of Male Rats

Subacute Exposure to Low Pb Doses Promotes Oxidative Stress in the Kidneys and Copper Disturbances in the Liver of Male Rats

Nickel as a potential disruptor of thyroid function: benchmark modelling of human data

Effects of Endocrine-Disrupting Heavy Metals on Human Health

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