Hemosiderosis

Female rats exposed acutely to 100 ppm 1,2-dibromoethane for up to seven exposures (see Section 2.2.1.1) had splenic congestion and hemosiderosis no changes in hematopoietic or lymphoid elements were described (Rowe et al. 1952). 

Parenteral administration of Fe + salts is indicated only when adequate oral replacement is not possible. There is a risk of overdosage with iron deposition in tissues (hemosiderosis). The binding capacity of transferrin is limited and free Fe + is toxic. Therefore, Fe + complexes are employed that can donate Fe + directly to transferrin or can be phagocytosed by macrophages, enabling iron to be incorporated into ferritin stores. Possible adverse effects are, with i.m injection persistent pain at the injection site and skin discoloration with i.v. injection flushing, hypotension, anaphylactic shock. 

When rats were exposed to low doses (0.4-3.1 mg/kg/day) of 1,3-DNB for 16 weeks, no overt signs of acute toxicity were seen (Cody et al. 1981). There was, however, a moderate decrease in hemoglobin levels after weeks 5 and 10, but they returned to control levels by week 14 (Cody et al. 1981). Splenic hemosiderosis was observed in all groups of rats treated with 0.75-6 mg 1,3-DNB by gavage for 12 weeks, including controls (Linder et al. 1986). Splenic hemosiderosis, which was minimal in controls and moderate to moderately severe at the highest dose level, is consistent with hemolytic anemia. No chronic-duration studies were located. 

The intermediate oral MRL was based on a LOAEL for splenic hemosiderosis in male rats administered 0.75 mg/kg/day 1,3-DNB by gavage in acetone/corn oil solution 5 days/week for 12 weeks (Linder et al. 1986). This dose-related response was minimal in controls and moderate to moderately severe at the highest dose level tested, 6 mg/kg/day. Splenic enlargement was also reported at 1.5 mg/kg/day. Adverse testicular effects were observed with doses of 1,3-DNB >1.5 mg/kg/day. Altered spermatogenesis was noted at >3 mg 1,3- DNB/kg/day. The observed splenic effects are considered secondary to the hematoxicity of 1,3-DNB and are supported by increased erythropoietic activity in rats in a study by Blackburn et al. (1988) and hemosiderosis in rats in a study by Cody et al. (1981), and are consistent with hemolytic anemia. The hematological effects of... 

Continuous exposure of rats by inhalation to 0.0055 and 0.3mg/m for 100 days resulted in methemoglobinemia, lowered erythrocyte hemoglobin, leukopenia and reticulocytosis, and reduced muscle chronaxie. Doses up to 500mg/kg administered by gavage to rats and mice for 13 weeks caused cyanosis and decreased motor activity, as well as hemosiderosis in the spleen liver, kidney, and testes. Bone marrow hyperplasia was observed in rats, and mice had increased hematopoiesis in the liver. In general, all toxic effects could be attributed to chronic methemoglobinemia, erythrocyte destruction, and erythrophagocytosis. 

In inhalation studies conducted by the National Toxicology Program, acute, subchronic, and chronic effects of ethyl bromide were examined in mice and rats. All mice and three of five female rats died before the end of a 4-hour exposure to 5000 ppm rats and mice exposed to 2 000 ppm 6 hours/day died before the end of 14-day studies. In 14-week studies, 1600 ppm was lethal to some animals and caused compound-related lesions including muscle atrophy and atrophy of the testis and uterus thought to be secondary to body weight loss rats also had minimal to moderate multifocal mineralization in the cerebellum and minimal-to-severe hemosiderosis of the spleen. 

Hemochromatosis hemosiderosis hemolytic anemias known hypersensitivity to any ingredients. 

Iron overload Unwarranted therapy with parenteral iron will cause excess storage of iron with the consequent possibility of exogenous hemosiderosis. 

Contraindications Hemochromatosis, hemosiderosis, hemolytic anemias, peptic ulcer disease, regional enteritis, ulcerative colitis... 

An intake of 25—75 mg Fe d may be safe. Long term iron overload has been noted in South Africa (Bantu siderosis). Ingestion of up to 200 mg Fe d-1 may be the result of eating food cooked in iron pots or drinking Kaffir beer containing 15-120 mg Fe 1 1. Ethiopians have a high iron intake (up to 500 mg d-1), but as siderosis is not common, much of this iron must be unavailable.33 This type of hemosiderosis should be treated by preventative measures to restrict the amount of iron in the diet.48... 

Serum Total Iron and Total Iron Binding Capacity The results for the determination of serum total iron and total iron-binding capacity of rats fed treatment diets for 18 months are also listed in Table VI. A significant increase in serum total iron was detected in rats fed the Maillard browned egg albumin over their control group. Increased serum total iron with normal total iron binding capacity is associated with hemolytic anemia, hemochromatosis, hemosiderosis, and hepatitis (30 ). On the basis of other clinical and histopathological data, however, none of these causes are likely. 

However, hemosiderosis and congestion of the spleen were observed at 25 mg/kg/day. In another intermediate-duration study, hemoglobin, hematocrit, and the ratio of mean corpuscular volume to mean corpuscular hemoglobin (MCV/MCH) were increased in rats given 5, 10, or 20 mg/kg/day DNOC for 90 days (Den Tonkelaar et al. 1983). The highest dose also resulted in increased erythrocyte count and decreased total leukocyte and lymphocyte counts. The reason for the different results in these studies is not known. 

Beeching, JJ., Hart, H.H., Synek, B.J., Bremner, DA. A patient with hemosiderosis and multiple hver abscesses due to Yersinia enterocoli-tica. Pathology 1985 17 530-532... 

Sallie, R.W., Reed, W.D., Shilkin, K.B. Confirmation of the efficacy of hepatic tissue iron index in differentiating genetic hemochromatosis from alcoholic liver disease complicated by alcoholic hemosiderosis. Gut 1991 32 207-210... 

Yoshida, K., Furihata, K., Takeda, S., Nakamura, A., Yamamoto, K., Morita, H., TUyamuta, S., Ikeda, S., Shimizu, N., Yanagisawa, N. A mutation in the ceruloplasmin gene is associated with systemic hemosiderosis in humans. Nature Genet. 1995 9 267-272... 

Unilateral sensorineural hearing loss occurred in a 7-year-old girl with idiopathic pulmonary hemosiderosis after she had taken hydroxychloroquine 100 mg bd for 2 years (17). 

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