Low doses of dietary lead are associated with a profound reduction in the time to the onset of puberty in female mice

Iavicoli, Ivo; Carelli, G; Stanek, Edward J.; Castellino, N; Li, Z.; Calabrese, E.J.

doi:10.1016/j.reprotox.2006.03.016

Cited by 27 publications

(20 citation statements)

References 12 publications

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“…However, our observations are consistent with analyses of the data of the Third National Health and Nutrition Examination Survey showing that environmental lead exposure was related to retarded pubic hair development in girls (Selevan et al, 2003;Wu et al, 2003). Studies in rats have shown an inhibiting effect of lead on pubertal development in the female (Dearth et al, 2002;Iavicoli et al, 2006;Pine et al, 2006). Possible underlying mechanisms might include the inhibition by lead of the binding of estradiol to estrogen receptor-a, observed in human cells in vitro (Martin et al, 2003), and decreased serum concentrations of insulin-like growth factor-1, LH and estradiol, which in turn may delay the onset or progression of puberty.…”

Section: Discussionsupporting

confidence: 91%

Internal exposure to pollutants and sexual maturation in Flemish adolescents

Hond

Dhooge

Bruckers

et al. 2010

J Expo Sci Environ Epidemiol

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Flanders is densely populated with much industry and intensive farming. Sexual maturation of adolescents (aged 14-15 years) was studied in relation to internal exposure to pollutants. Serum levels of pollutants and sex hormones were measured in 1679 participants selected as a random sample of the adolescents residing in the study areas. Data on sexual development were obtained from the medical school examination files. Self-assessment questionnaires provided information on health, use of medication and lifestyle factors. In boys, serum levels of hexachlorobenzene (HCB), p,p 0 -DDE and polychlorinated biphenyls (sum of marker PCB138, 153 and 180) were significantly and positively associated with pubertal staging (pubic hair and genital development). Higher levels of serum HCB and blood lead were associated with, respectively, a lower and a higher risk of gynecomastia. In girls, significant and negative associations were detected between blood lead and pubic hair development; higher exposure to PCBs was significantly associated with a delay in timing of menarche. Environmental exposures to pollutants at levels actually present in the Flemish population are associated with measurable effects on pubertal development. However, further understanding of toxic mode of action and sensitive windows of exposure is needed to explain the current findings.

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Section: Discussionsupporting

confidence: 91%

Internal exposure to pollutants and sexual maturation in Flemish adolescents

Hond

Dhooge

Bruckers

et al. 2010

J Expo Sci Environ Epidemiol

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“…While the fish kept in the ponds and exposed to lead did not show any statistically significant differences in the GSI value after 12 and after 24 months of the exposure (Table 3), Prussian carps kept in aquariums showed statistically significant differences in the values of the GSI after 12 months of the exposure (LuszczekTrojnar et al 2014). The influence of lead on the endocrinological changes in mammals (Iavicoli et al 2006) and fish (Spieler et al 1995;Rademacher et al 2003;Sloman et al 2005) was analyzed on many occasions. In the present research, after 12 months of the exposure spontaneous secretion of LH ranged from 15 ± 6.8 to 45 ± 5.4 ng/ml, and after 24 months the secretion ranged from 23 ± 5.3 to 45 ± 7.7 ng/ml.…”

Section: Monthsmentioning

confidence: 99%

“…Other observed effects of lead contamination in animals include neurological, gastrointestinal, reproductive, circulatory, immunological, histopathological, and histochemical disorders (Iavicoli et al 2006;Mobarak and Sharaf 2011;Sharma et al 2011;Steuerwald et al 2014). The negative influence of lead on organisms is observed not only in the case of the use of large doi: 10.17221/8526-CJAS doses of this metal, but also very frequently in the case of chronic exposure to its small doses.…”

Section: Introductionmentioning

confidence: 99%

“…Lead can easily penetrate cell membranes and cross the blood-brain barrier (Steuerwald et al 2014). It is a known endocrine-disrupting chemical in mammals and is believed to produce this effect through the hypothalamic-pituitary axis (Lucchi et al 1981;Iavicoli et al 2006). Weber (1993) observed that multiple effects on reproductive behaviour and overall reproductive success in adult fathead minnows, where lead suppressed spermatocyte production and retarded ovarian development, decreased the number of eggs oviposited, increased interspawn periods, and suppressed embryo development.…”

Section: Introductionmentioning

confidence: 99%

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Influence of long-term exposure to lead on its accumulation and elimination from tissues and on selected reproductive parameters in the Prussian carp (Carassius gibelio B.) in pond environment

Łuszczek‐Trojnar¹,

Drąg‐Kozak²,

Socha³

et al. 2015

Czech J. Anim. Sci.

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ABSTRACT:The bioaccumulation of lead in selected tissues of Prussian carp kept in pond condition during 12 and 24 months of exposure to different doses (8, 13, 24, and 49 mg/kg) of this metal in feed and its elimination from tissues during the following 12-month depuration period was studied. Additionally gonadosomatic index and luteinizing hormone (LH) secretion, as the effect of exposure to Pb, were examined. The concentration of lead in all the studied tissues, except for the gonads, correlated positively with the metal concentration in the diet, and the maximum level was usually achieved after 3 months of the exposure. The highest levels of lead, i.e. 2.1 ± 0.14 mg/kg, were found in the posterior intestine in the 15 th month of the exposure, followed by bones, scales and kidneys, in which the level of lead amounted to 1.8 ± 0.20, 1.22 ± 0.07, and 1.17 ± 0.17 mg/kg, respectively. The negative effect of chronic exposure to lead was manifested by a significantly higher spontaneous LH secretion in groups exposed to 24 and 49 mg/kg of lead and a higher LH secretion level 6 h after the stimulating secretion. After 12 months of exposure and 12 months of depuration, as well as after 24 months of exposure, the effects of lead on LH secretion were not observed. Environmental lead can be a potent endocrine disruptor, which may have an adverse impact on fish reproduction. Prussian carps become resistant to the negative effects of lead with age and their organisms cope by reaching a state of homeostasis.

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“…For example, this suggests that the EPA would consider possible harm related to an hormetic/ biphasic dose-response, but not if benefits occurred. The U.S. EPA could accept data showing a low dose hormetic stimulation leading to adverse health effects (e.g., increased prostate gland size [120] or significant acceleration in a developmental process such as the onset of puberty [133,134]). In contrast, the U.S. EPA would ignore the hormetic response when it resulted in a reduction in a population-based risk (reduction in tumor incidence).…”

Section: The Default Model In Risk Assessmentmentioning

confidence: 99%

Toxicology rewrites its history and rethinks its future: Giving equal focus to both harmful and beneficial effects

Calabrese

2011

Enviro Toxic and Chemistry

120

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Abstract-This paper assesses how medicine adopted the threshold dose-response to evaluate health effects of drugs and chemicals throughout the 20th century to the present. Homeopathy first adopted the biphasic dose-response, making it an explanatory principle. Medicine used its influence to discredit the biphasic dose-response model to harm homeopathy and to promote its alternative, the threshold dose-response. However, it failed to validate the capacity of its model to make accurate predictions in the low-dose zone. Recent attempts to validate the threshold dose-response indicate that it poorly predicts responses below the threshold. The long marginalized biphasic/hormetic dose-response model made accurate predictions in these validation studies. The failure to accept the possibility of the hormetic-biphasic dose-response during toxicology's dose-response concept formative period, while adopting the threshold model, and later the linear no-threshold model for carcinogens, led toxicology to adopt a hazard assessment process that involved testing only a few very high doses. This created the framework that toxicology was a discipline that only studied harmful responses, ignoring the possibility of benefit at low doses by the induction of adaptive mechanisms. Toxicology needs to assess the entire dose-response continuum, incorporating both harmful and beneficial effects into the risk assessment process. Environ. Toxicol. Chem.

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Low doses of dietary lead are associated with a profound reduction in the time to the onset of puberty in female mice

Cited by 27 publications

References 12 publications

Internal exposure to pollutants and sexual maturation in Flemish adolescents

Internal exposure to pollutants and sexual maturation in Flemish adolescents

Influence of long-term exposure to lead on its accumulation and elimination from tissues and on selected reproductive parameters in the Prussian carp (Carassius gibelio B.) in pond environment

Toxicology rewrites its history and rethinks its future: Giving equal focus to both harmful and beneficial effects

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