Vol. 119, No. 5 PerspectivesOpen AccessRedefining Low Lead Levels Ivo Iavicoli Edward J. Calabrese Ivo Iavicoli Search for more papers by this author and Edward J. Calabrese Search for more papers by this author Published:1 May 2011https://doi.org/10.1289/ehp.1103489Cited by:1AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit In the January 2011 issue of EHP, Giddabasappa et al. (2011) reported that gestational lead exposure (GLE) of C57BL/6 mice produced selective nonmonotonic increases in the numbers of rods and cone bipolar cells (BCs) in the adult retina. Interestingly, this increase was characterized by an inverted U-shaped dose–response curve. Moreover, findings of this study showed that GLE increases and prolongs proliferation of retinal progenitor cells (RPCs) without decreasing apoptosis. Consequently, this phenomenon produced an adult retina with normal lamination and a selectively increased number of rods and BCs. These results should be considered to define a more adequate risk assessment at low levels of lead exposure. In fact, other published articles have indicated that lead induced a biphasic dose–response relationship (Calabrese and Baldwin 2003).In experiments in Swiss mice using low-level lead exposures similar to and lower than those used by Giddabasappa et al. (2011), we observed an increase in the number of red blood cells, in female gestational parameters, and in Th1 cytokine levels (Iavicoli et al. 2003, 2004, 2006a, 2006b). For this reason, it would be interesting if Giddabasappa et al. could verify this increase in the number of neurons in the rod-signaling pathway at even lower blood lead levels (< 10 μg/dL). The findings of our studies were also implicated over several generations.In any case, we agree with Giddabasappa et al. (2011) that their findings, as ours, raise complex issue for toxicologists, pediatricians, public health regulators, and risk assessors who need to incorporate the occurrence of such U-shaped dose responses in the hazard and risk assessment process. In this context, these findings could be explained by the hormesis phenomenon, which is a dose–response relationship characterized by low-dose stimulation and high-dose inhibition (Calabrese 2008, 2009).ReferencesCalabrese EJ. 2008. Hormesis: why it is important to toxicology and toxicologists. Environ Toxicol Chem 27:1451-147418275256. Crossref, Medline, Google ScholarCalabrese EJ. 2009. Getting the dose-response wrong: why hormesis became marginalized and the threshold model accepted. Arch Toxicol 83:227-24719234688. Crossref, Medline, Google ScholarCalabrese EJ, Baldwin LA. 2003. Inorganics and hormesis. Crit Rev Toxicol 33:215-30412809427. Crossref, Medline, Google ScholarGiddabasappa A, Hamilton WR, Chaney S, Xiao W, Johnson JE, Mukherjee Set al.. 2011. Low-level gestational lead exposure increases retinal progenitor cell proliferation and rod photoreceptor and bipolar cell neurogenesis in mice. Environ Health Perspect 119:71-7720840909. Link, Google ScholarIavicoli I, Carelli G, Stanek EJ, Castellino N, Calabrese EJ. 2003. Effects of low doses of dietary lead on red blood cell production in male and female mice. Toxicol Lett 137:193-19912523962. Crossref, Medline, Google ScholarIavicoli I, Carelli G, Stanek EJ, Castellino N, Calabrese EJ. 2006a. Below background levels of blood lead impact cytokine levels in male and female mice. Toxicol Appl Pharmacol 210:94-9916289177. Crossref, Medline, Google ScholarIavicoli I, Carelli G, Stanek EJ, Castellino N, Calabrese EJ. 2004. Effects of low doses of dietary lead on puberty onset in female mice. Reprod Toxicol 19:35-4115336710. Crossref, Medline, Google ScholarIavicoli I, Carelli G, Stanek EJ, Castellino N, Li Z, Calabrese EJ. 2006b. Low doses of dietary lead are associated with a profound reduction in the time to the onset of puberty in female mice. Reprod Toxicol 22:586-59016713174. Crossref, Medline, Google ScholarFiguresReferencesRelatedDetailsCited By Corsetti G, Romano C, Stacchiotti A, Pasini E and Dioguardi F (2016) Endoplasmic Reticulum Stress and Apoptosis Triggered by Sub-Chronic Lead Exposure in Mice Spleen: a Histopathological Study, Biological Trace Element Research, 10.1007/s12011-016-0912-z, 178:1, (86-97), Online publication date: 1-Jul-2017. Vol. 119, No. 5 May 2011Metrics About Article Metrics Publication History Originally published1 May 2011Published in print1 May 2011 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. 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