Tissue Manganese Concentrations in Lactating Rats and Their Offspring Following Combined in Utero and Lactation Exposure to Inhaled Manganese Sulfate

Abstract

There is little information regarding the tissue distribution of manganese in neonates following inhalation. This study determined tissue manganese concentrations in lactating CD rats and their offspring following manganese sulfate (MnSO4) aerosol inhalation. Except for the period of parturition, dams and their offspring were exposed to air or MnSO4 (0.05, 0.5, or 1 mg Mn/m3) for 6 h/day, 7 days/week starting 28 days prior to breeding through postnatal day (PND) 18. Despite increased manganese concentrations in several maternal tissues, MnSO4 inhalation exposure did not affect body weight gain, terminal (PND 18) body weight, or organ weights in the dams. Exposure to MnSO4 at 1 mg Mn/m3 resulted in decreased pup body weights on PND 19 and decreased brain weights in some PND 14 to PND 45 pups. Exposure to MnSO4 at > or =0.05 mg Mn/m3 was associated with increased stomach content, blood, liver, and skull cap manganese concentrations in PND 1 pups, increased brain, lung, and femur manganese concentrations in PND 14 pups, and elevated olfactory bulb, cerebellum, and striatum manganese concentrations in PND 19 pups. When compared to controls, MnSO4 exposure to > or =0.5 mg Mn/m3 increased liver and blood manganese concentrations in PND 14 pups and increased liver, pancreas, and femur manganese concentrations in PND 19 pups. Manganese concentrations returned to control values in all offspring tissues by PND 45 +/- 1. Our data demonstrate that neonatal tissue manganese concentrations observed following MnSO4 inhalation are dependent on the MnSO4 exposure concentration and the age of the animal.

Association between Manganese Exposure through Drinking Water and Infant Mortality in Bangladesh

“…First, human studies have not looked at the association between manganese and infant mortality. As noted in the introduction, manganese might affect weight gain of neonates, as seen in several animal studies (Dorman et al 2000, 2005; Pappas et al 1997; Rehnberg et al 1980); this would affect infant mortality, but not birth weight or stillbirths. Second, these studies do not have highly exposed participants.…”

“…Specifically, subcutaneous and intravenous exposure to manganese was associated with both increased resorptions of fetuses and decreased birth weight (Colomina et al 1996; Sanchez et al 1993). Although oral and inhalation exposures did not have embryotoxic or fetotoxic effects, high doses through both of these mediums reduced weight gain (Dorman et al 2000, 2005; Pappas et al 1997) and decreased survival (Rehnberg et al 1980) in neonatal rats.…”

Adequacy and Consistency of Animal Studies to Evaluate the Neurotoxicity of Chronic Low-Level Manganese Exposure in Humans

“…Thus, the extent to which these animal studies may be of utility to understand the risk for adverse effects in humans suffering chronic low-level environmental exposures is not clear. Some recent animal studies have started to address the potential effects of low-level environmental exposures by administering environmentally relevant doses via exposure routes important in humans, though these studies are relatively few in number (Dorman et al 2005;Normandin et al 2002Normandin et al , 2004Salehi et al 2003;Tapin et al 2005).…”

Update on a Pharmacokinetic-Centric Alternative Tier II Program for MMT—Part I: Program Implementation and Lessons Learned

“…To further assess this concern, the Hamner exposed rat dams and their offspring to air or MnSO 4 (0.05, 0.5, or 1 mg Mn/m 3 ) for 6 hr/day, 7 days/week starting 28 days prior to breeding and from PND 1 through 18. The experimentally determined manganese concentration in neonatal striatum and the model-predicted AUC for this brain region did not imply significantly higher exposures in the pups when compared to those in adults up to the inhaled dose of 1 mg/m 3 [55, 56]. Despite the virtual absence of basal biliary excretion in neonatal rats, they appear to induce their biliary excretion when challenged with excess manganese through the oral route [57].…”