Studies on Acute Iron Poisoning

Abstract

The widespread use of hematinics has increased the hazard of iron poisoning of infants and children. The symptoms are similar in humans and in some animal species, thus making it possible to duplicate the events of accidental poisoning in the laboratory and to evaluate antidotal procedures. Materials and MethodsTwelve mongrel dogs in good health were used.The animals were maintained on a standard diet but were fasted for 24 hours before experimentation. To avoid vomiting and to simulate the delay in treatment that might be expected in poisoned children, solutions of ferrous sulfate were introduced directly into the jejunum of the dogs by syringe and needle after a midline exposure of the abdominal cavity. In this way the dose of iron was known with certainty.The experiments were performed under light pentobarbital anesthesia (30 mg/kg. intravenously). In some instances small supplementary doses were necessary. In each dog an endotracheal tube was inserted to prevent aspiration of saliva and gastric contents, though this was not uniformly successful.To determine the most effective mode of treat¬ ment with the antidotes selected, a variety of schedules were used. Two doses of ferrous sulfate in 25% solution were administered, giving 200 and 300 mg. per kilogram of elemental iron. Both of these doses were considered to be lethal and certainly would have represented extreme danger to an infant ingesting such amounts. By administering large quantities of iron that would be over¬ whelmingly toxic, there could be little question of individual resistance.The antidotes used were as follows : 1. NaaHPO, · 2 H20 in 20% solution (disodium orthophosphate dihydrate) 2. Edathamil calcium-disodium in 2.0% solu¬ tion (calcium disodium ethylenediaminetetraacetate) 3. Dog plasma, freshly drawn 4. Dextrans of molecular weight about 38,000 and about 8,000 Serum iron concentrations were determined by the method of Burch, Lowry, and Bessey,1 and the latent iron-binding capacity of the sera by the method of Rath and Finch.2 Microhematocrit values were obtained serially with the use of an International Hematocrit centrifuge. Blood pH de¬ terminations were made with a Beckman pH meter.Dogs that died were examined shortly after death for gross pathological changes. Microscopic studies were made on selected tissues using hematoxylin-eosin and Gomori iron stains.Samples of venous blood were removed for laboratory study before administration of the ferrous sulfate and at 30-, 60-, or 120-minute in¬ tervals thereafter during the treatment of the animals.The serum iron concentrations recorded for each dog are illustrated in the Figure. ResultsControls.-Three dogs served as control subjects. The dosage schedule and labora¬ tory results are listed in Table 1. Dog 1-a was given a dose of ferrous sul¬ fate equal to 200 mg/kg. of elemental iron. Dog 1-b and Dog 1-c received an equivalent of 300 mg/kg. of elemental iron. Death in shock was rapid. The packed-cell volumes increased within 30-60 minutes as did the concentrations of serum iron. The very ...

Scientific Opinion on the safety and efficacy of iron compounds (E1) as feed additives for all species: ferrous sulphate heptahydrate based on a dossier submitted by Kronos International, Inc.

“…Dogs ingesting between 20 and 60 mg elemental iron/kg bw can develop mild clinical signs. In mongrels, intrajejunal doses of 200300 mg Fe/kg bw were lethal in 56 h (Bronson and Sisson, 1960). When the amount of elemental iron ingested is greater than 60 mg/kg bw, serious clinical signs can develop.…”

Scientific Opinion on the safety and efficacy of iron compounds (E1) as feed additives for all species: Ferrous sulphate monohydrate based on a dossier submitted by Kronos International, Inc.

“…Higher doses of ferrous sulphate (600 mg Fe/kg bw) caused death, but 1500 mg iron from ferrous carbonate/kg bw had no effect in dogs (D'Arcy and Howard, 1962). In mongrels, intrajejunal doses of 200300 mg/kg bw were lethal in 56 h (Bronson and Sisson, 1960). The median lethal dose (LD 50 ) of ferrous sulphate heptahydrate in cats was estimated to be 800 mg/kg bw (Hoppe et al, 1955).…”

Synthetic Chelating Agents in Iron Metabolism*

“…There have been reports on the use of EDTA in this connection, both in animal experiments and also in accidental iron poisoning in children (24,25 (7) indicate that tissue iron becomes available to chelates only when an excess is present. The rate of plasma iron turnover did not correlate with the amount of iron excreted after administration of chelate.…”