Comparative Toxicology of Iron Compounds

“…Studies from our group and others show that intestinal iron absorption is elevated in pre-weanling animals [ 29 , 37 , 49 , 50 ], likely increasing susceptibility to iron toxicity. The LD50 for ferrous sulfate in adult rats is estimated to be 780–1100 mg iron/kg BW [ 51 , 52 ], where reduced body weight was observed in surviving rats [ 52 ]. In comparison, few studies have investigated the growth response upon excess iron provision in pre-weanling animals.…”

Section: Discussionmentioning

confidence: 99%

Trace Element Interactions, Inflammatory Signaling, and Male Sex Implicated in Reduced Growth Following Excess Oral Iron Supplementation in Pre-Weanling Rats

2022

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Iron supplements are frequently provided to infants in high-income countries despite low incidence of iron deficiency. There is growing concern regarding adverse health and development outcomes of excess iron provision in early life. Excess iron may directly damage developing organs through the formation of reactive oxygen species, alter systemic inflammatory signaling, and/or dysregulate trace mineral metabolism. To better characterize the in vivo effects of excess iron on development, we utilized a pre-weanling rat pup model. Lewis rat litters were culled to eight pups (four males and four females) and randomly assigned to daily supplementation groups receiving either vehicle control (CON; 10% w/v sucrose solution) or ferrous sulfate (FS) iron at one of the following doses: 10, 30, or 90 mg iron/kg body weight—FS-10, FS-30, and FS-90, respectively—from postnatal day (PD) 2 through 9. FS-90 litters, but not FS-30 or FS-10, failed to thrive compared to CON litters and had smaller brains on PD 10. Among the groups, FS-90 liver iron levels were highest, as were white blood cell counts. Compared to CON, circulating MCP-1 and liver zinc were increased in FS-90 pups, whereas liver copper was decreased. Growth defects due to excess FS provision in pre-weanling rats may be related to liver injury, inflammation, and altered trace mineral metabolism.

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“…7 In animal studies, higher doses are required for lethal toxicity with iron complex preparations than with other oral iron preparations. 7,8 Although iron accounts for a substantial proportion of deaths from accidental ingestions in children, there were no major effects or deaths in 810 potentially toxic expos-ures to polysaccharide-iron complex reported to American poison control centres. 9 This reduced toxicity with polysaccharideiron complex products suggests they may be less effectively absorbed than other preparations.…”

Section: Iron Complexesmentioning

confidence: 99%