1141 Mangafodipir Mangafodipir is a contrast agent delivered intravenously to enhance contrast in magnetic resonance imaging (MRI) of the liver. It has two parts, paramagnetic manganese (II) ions and the chelating agent fodipir (dipyridoxyl diphosphate, DPDP). Normal liver tissue absorbs the manganese more than abnormal or cancerous tissue. The manganese shortens the longitudinal relaxation time (called T1), making the normal tissue appear brighter in MRIs. This enhanced contrast allows lesions to be more easily identified. Acute toxicity studies in mice, rats and dogs using IV administration showed mangafodipir to have low to moderate toxicity. Repeat dose toxicity studies were conducted in rats, cynomologous monkeys and dogs. The liver and to a lesser extent the kidney were target organs of toxicity. 140678-14-4 160036 C22H27MnN4Na3O14P2 757.007260 Liquid Oral (L228) ; inhalation (L228) Manganese is a cellular toxicant that can impair transport systems, enzyme activities, and receptor functions. It primarily targets the central nervous system, particularily the globus pallidus of the basal ganglia. It is believed that the manganese ion, Mn(II), enhances the autoxidation or turnover of various intracellular catecholamines, leading to increased production of free radicals, reactive oxygen species, and other cytotoxic metabolites, along with a depletion of cellular antioxidant defense mechanisms, leading to oxidative damage and selective destruction of dopaminergic neurons. In addition to dopamine, manganese is thought to perturbations other neurotransmitters, such as GABA and glutamate. In order to produce oxidative damage, manganese must first overwhelm the antioxidant enzyme manganese superoxide dismutase. The neurotoxicity of Mn(II) has also been linked to its ability to substitute for Ca(II) under physiological conditions. It can enter mitochondria via the calcium uniporter and inhibit mitochondrial oxidative phosphorylation. It may also inhibit the efflux of Ca(II), which can result in a loss of mitochondrial membrane integrity. Mn(II) has been shown to inhibit mitochondrial aconitase activity to a significant level, altering amino acid metabolism and cellular iron homeostasis. (L228) Metabolism of organophosphates occurs principally by oxidation, by hydrolysis via esterases and by reaction with glutathione. Demethylation and glucuronidation may also occur. Oxidation of organophosphorus pesticides may result in moderately toxic products. In general, phosphorothioates are not directly toxic but require oxidative metabolism to the proximal toxin. The glutathione transferase reactions produce products that are, in most cases, of low toxicity. Paraoxonase (PON1) is a key enzyme in the metabolism of organophosphates. PON1 can inactivate some organophosphates through hydrolysis. PON1 hydrolyzes the active metabolites in several organophosphates insecticides as well as, nerve agents such as soman, sarin, and VX. The presence of PON1 polymorphisms causes there to be different enzyme levels and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effect of organophosphate exposure. No indication of carcinogenicity to humans (not listed by IARC). Mangafodipir is a contrast agent delivered intravenously to enhance contrast in magnetic resonance imaging (MRI) of the liver. (L231) Chronic Inhalation: 0.0003 mg/m3 (L134) Manganese mainly affects the nervous system and may cause behavioral changes and other nervous system effects, which include movements that may become slow and clumsy. This combination of symptoms when sufficiently severe is referred to as “manganism”. (L228) Manganese mainly affects the nervous system and may cause behavioral changes and other nervous system effects, which include movements that may become slow and clumsy. This combination of symptoms when sufficiently severe is referred to as “manganism”. (L228) 2009-06-19T21:58:21Z 2014-12-24T20:23:12Z Alpha-2-macroglobulin (P01023) Serum albumin (P02768) Serotransferrin (P02787) Superoxide dismutase [Mn], mitochondrial (P04179) (L228) Mangafodipir true Alpha-2-macroglobulin (P01023) Serum albumin (P02768) Serotransferrin (P02787) (L228) [Na+].[Na+].[Na+].[Mn++].CC1=C([O-])C(CN(CCN(CC([O-])=O)CC2=C(COP(O)([O-])=O)C=NC(C)=C2[O-])CC([O-])=O)=C(COP(O)(O)=O)C=N1 C22H27MnN4Na3O14P2 InChI=1S/C22H32N4O14P2.Mn.3Na/c1-13-21(31)17(15(5-23-13)11-39-41(33,34)35)7-25(9-19(27)28)3-4-26(10-20(29)30)8-18-16(12-40-42(36,37)38)6-24-14(2)22(18)32;;;;/h5-6,31-32H,3-4,7-12H2,1-2H3,(H,27,28)(H,29,30)(H2,33,34,35)(H2,36,37,38);;;;/q;+2;3*+1/p-5 InChIKey=BENFPBJLMUIGGD-UHFFFAOYSA-I 757.3231 757.007258277 Exogenous Liquid 140690