Siblings with pediatric sodium chlorite toxicity causing methemoglobinemia, renal failure and hemolytic anemia.

INTRODUCTION: Over the past decade, Miracle Mineral Solution (sodium chlorite) has been promoted as a cure-all for many conditions. CASE REPORT: A 9-year-old boy presented with his brother after they accidentally ingested a small amount of undiluted 22.4% sodium chlorite. Symptoms included nausea, vomiting, diarrhea, and dyspnea. Oxygen saturation remained 71% despite supplemental oxygen (15L/min). The patient was noted to have dark chocolate-appearing blood, minimal urine output, diffuse pallor and cyanosis. He developed methemoglobinemia, renal failure requiring renal replacement therapy and hemolysis requiring blood transfusion. DISCUSSION: These are the 7th and 8th reported cases of sodium chlorite toxicity by ingestion and the second and third in children. Takeaway for Physicians: Miracle Mineral Solution is a commonly purchased potentially lethal compound that can cause methemoglobinemia with respiratory failure, hemolytic anemia requiring transfusion and renal failure requiring dialysis.

Cyanosis Due to Methemoglobinemia as the Presenting Sign of Glucose-6-Phosphate Dehydrogenase Deficiency in a Child: Diagnostic and Clinical Implications.

A previously healthy 3-year-old boy presented with pallor, jaundice, cyanosis, and a 24-hour history of vomiting and anorexia following fava bean ingestion. Clinical examination and laboratory findings were consistent with severe nonimmune hemolytic anemia with methemoglobinemia. Given the patient's history, a previously unrecognized glucose-6-phosphate dehydrogenase deficiency was suspected and diagnosed. The aim of this article is to delineate the possible coexistence of methemoglobinemia and glucose-6-phosphate dehydrogenase deficiency in children presented with acute hemolysis and discuss its management while reviewing the existing literature.

Fatal Methemoglobinemia Due to Acute Inhalation of Methyl Nitrite in an Industrial Accident.

Methyl nitrite is suggested to cause methemoglobinemia by generating methemoglobin, which may be lethal when the methemoglobin concentration exceeds 70%. However, intoxication with methyl nitrite is seldom reported compared with that with other nitrites. Here, we present an industrial accident involving methyl nitrite inhalation during its synthesis process that resulted in three fatalities and one survivor. The autopsy revealed conspicuous blue-gray discoloration in various parts of the body, including the skin, airway mucosa, vessels, brain, heart, and among other areas. The toxicological tests on the deceased showed methemoglobin concentrations in the blood over the lethal level and increased nitrite ion levels in the blood, gastric contents, liver, and lung tissue compared with those in control samples. The cause of death was determined to be methemoglobinemia-induced hypoxia due to methyl nitrite inhalation. This report provides evidence that in methyl nitrite intoxication, exposure duration has a significant influence on the postmortem changes and likelihood of a fatal outcome may be related to the age of the victim. More attention is required regarding the industrial hazards of this substance.

Congenital methemoglobinaemia due to Hb F-M-Fort Ripley in a preterm newborn.

Methemoglobinaemia is a rare cause of cyanosis in newborns. Congenital methemoglobinaemias due to M haemoglobin or deficiency of cytochrome b5 reductase are even rarer. We present a case of congenital methemoglobinaemia presenting at birth in a preterm infant. A baby boy born at 29 weeks and 3 days of gestation had persistent central cyanosis immediately after delivery, not attributable to a respiratory or cardiac pathology. Laboratory methemoglobin levels were not diagnostic. Cytochrome b5 reductase levels were normal and a newborn screen was unable to pick up any abnormal variants of fetal haemoglobin. Genetic testing showed a γ globin gene mutation resulting in the M haemoglobin, called Hb F-M-Fort Ripley. The baby had no apparent cyanosis at a corrected gestational age of 42 weeks. Although rare, congenital methaemoglobin aemia should be considered in the differential in a preterm with central cyanosis and investigated with genetic testing for γ globin chain mutations if other laboratory tests are non-conclusive.

Hb M-Iwate in an Indian family.

BACKGROUND: High performance liquid chromatography in a newborn girl with congenital cyanosis and a unilateral cleft palate revealed a variant hemoglobin with retention time of 4.8 min, similar to hemoglobin Q-India. Since hemoglobin Q-India did not explain the cyanosis, further investigations were initiated. METHODS: Sequencing of α-globin genes revealed hemoglobin M-Iwate ([α87 (F8) His → Tyr]) that was confirmed on restriction enzyme analysis. RESULTS: Hemoglobin M-Iwate is a rare methemoglobinemic variant formed due to a point mutation in the α-globin gene. Primarily reported from the Iwate prefecture of Japan, there have been occasional case reports from other regions as well. Inherited methemoglobinemia finds only rare mention in Indian literature while hemoglobin M-Iwate has not been reported from India. CONCLUSIONS: This case illustrates the step-wise logical diagnostic approaches necessary to elucidate the cause of methemoglobinemia in an otherwise healthy child with cyanosis.

Antagonism of Acute Sulfide Poisoning in Mice by Nitrite Anion without Methemoglobinemia.

There are currently no FDA-approved antidotes for H2S/sulfide intoxication. Sodium nitrite, if given prophylactically to Swiss Webster mice, was shown to be highly protective against the acute toxic effects of sodium hydrosulfide (∼LD40 dose) with both agents administered by intraperitoneal injections. However, sodium nitrite administered after the toxicant dose did not detectably ameliorate sulfide toxicity in this fast-delivery, single-shot experimental paradigm. Nitrite anion was shown to rapidly produce NO in the bloodstream, as judged by the appearance of EPR signals attributable to nitrosylhemoglobin and methemoglobin, together amounting to less than 5% of the total hemoglobin present. Sulfide-intoxicated mice were neither helped by the supplemental administration of 100% oxygen nor were there any detrimental effects. Compared to cyanide-intoxicated mice, animals surviving sulfide intoxication exhibited very short knockdown times (if any) and full recovery was extremely fast (∼15 min) irrespective of whether sodium nitrite was administered. Behavioral experiments testing the ability of mice to maintain balance on a rotating cylinder showed no motor impairment up to 24 h post sulfide exposure. It is argued that antagonism of sulfide inhibition of cytochrome c oxidase by NO is the crucial antidotal activity of nitrite rather than formation of methemoglobin.

Sodium nitrite potentiates renal oxidative stress and injury in hemoglobin exposed guinea pigs.

Methemoglobin-forming drugs, such as sodium nitrite (NaNO2), may exacerbate oxidative toxicity under certain chronic or acute hemolytic settings. In this study, we evaluated markers of renal oxidative stress and injury in guinea pigs exposed to extracellular hemoglobin (Hb) followed by NaNO2 at doses sufficient to simulate clinically relevant acute methemoglobinemia. NaNO2 induced rapid and extensive oxidation of plasma Hb in this model. This was accompanied by increased renal expression of the oxidative response effectors nuclear factor erythroid 2-derived-factor 2 (Nrf-2) and heme oxygenase-1 (HO-1), elevated non-heme iron deposition, lipid peroxidation, interstitial inflammatory cell activation, increased expression of tubular injury markers kidney injury-1 marker (KIM-1) and liver-fatty acid binding protein (L-FABP), podocyte injury, and cell death. Importantly, these indicators of renal oxidative stress and injury were minimal or absent following infusion of Hb or NaNO2 alone. Together, these results suggest that the exposure to NaNO2 in settings associated with increased extracellular Hb may potentiate acute renal toxicity via processes that are independent of NaNO2 induced erythrocyte methemoglobinemia.

Clinical spectrum and molecular basis of recessive congenital methemoglobinemia in India.

We report the clinical features and molecular characterization of 23 patients with cyanosis due to NADH-cytochrome b5 reductase (NADH-CYB5R) deficiency from India. The patients with type I recessive congenital methemoglobinemia (RCM) presented with mild to severe cyanosis only whereas patients with type II RCM had cyanosis associated with severe neurological impairment. Thirteen mutations were identified which included 11 missense mutations causing single amino acid changes (p.Arg49Trp, p.Arg58Gln, p.Pro145Ser, p.Gly155Glu, p.Arg160Pro, p.Met177Ile, p.Met177Val, p.Ile178Thr, p.Ala179Thr, p.Thr238Met, and p.Val253Met), one stop codon mutation (p.Trp236X) and one splice-site mutation (p.Gly76Ser). Seven of these mutations (p.Arg50Trp, p.Gly155Glu, p.Arg160Pro, p.Met177Ile, p.Met177Val, p.Ile178Thr, and p.Thr238Met) were novel. Two mutations (p.Gly76Ser and p.Trp236X) were identified for the first time in the homozygous state globally causing type II RCM. We used the three-dimensional (3D) structure of human erythrocyte NADH-CYB5R to evaluate the protein structural context of the affected residues. Our data provides a rationale for the observed enzyme deficiency and contributes to a better understanding of the genotype-phenotype correlation in NADH-CYB5R deficiency.

Identification of N-Hydroxy-para-aminobenzoic acid in a cyanotic child after benzocaine exposure.

CONTEXT: Methemoglobinemia (MetHb) after exposure to benzocaine (BZC) has been reported for more than 50 years, however the pathophysiologic mechanism has not been previously established. Direct administration of BZC to blood does not produce MetHb. After topical use, due to the lipophilicity and rapid acetylation in the tissue, little BZC reaches the liver for hepatic biotransformation. However, isolated human livers have been shown to produce MetHb forming N-hydroxyl metabolites from BZC. We report a case of BZC-induced MetHb with the first identification and quantification of the reactive metabolite responsible for the oxidative stress: N-Hydroxy-Para-amino benzoic acid (N-OH-PABA). CASE DETAILS: An 8 year old male was admitted to a hospital for an appendectomy. Several applications of BZC spray were used during multiple attempts at nasogastric tube placement. In various attempts to achieve local anesthesia, benzocaine spray was used in both nares and through the mouth aimed at the posterior oropharynx. The patient subsequently became cyanotic with an initial MetHb level of 32.9 %. Methylene blue was administered and the patient promptly responded with resolution of cyanosis. Blood taken within 20 min of the initial symptoms contained benzocaine (5.2ug/mL), bupivacaine (740ng/mL), lidocaine (530ng/mL), acetaminophen (12ug/mL), midazolam (60ng/mL), PABA and N-OH-PABA (35ng/mL). Serum was analyzed using Liquid Chromatography- Quadrupole Time-of-Flight Mass Spectrometry. Mass spectrometry was done using an electrospray ionization source run in negative and positive polarities. A reference standard for N-OH-PABA was synthesized for confirmation and quantification. DISCUSSION: The rare and idiopathic nature of methemoglobinemia after benzocaine use has made study of the pathophysiologic mechanism in humans difficult. Lack of understanding has brought calls for restriction of use of the widely used medication that may not be based on evidence. Our case presents several unique features: 1) benzocaine absorption after topical administration was documented with serum concentrations 2) confirmation of an in vivo formation of MetHb-forming n-hydroxyl-metabolite after benzocaine use and 3) the documentation of N-OH-PABA in humans within 20 min of MetHb post-benzocaine administration.

A 26-Week Toxicity Assessment of AIR001 (Sodium Nitrite) by Inhalation Exposure in Rats and by Intravenous Administration in Dogs.

Historically, nitrogen oxides (NOx) in food, drinking water, as well as in the atmosphere have been believed to be associated with adverse health consequences. More recently, NOx have been implicated in normal homeostatic regulation, and exogenous administration has been associated with health benefits. One such potential health benefit is the prospect that inhaled nitrite will lower pulmonary blood pressure (BP) in patients with pulmonary arterial hypertension (PAH), a disease with poor prognosis due to the lack of effective treatment. To characterize potential chronic toxicity associated with inhaled AIR001 (sodium nitrite) for use in the treatment of PAH, 26-week exposures to AIR001 were carried out by inhalation administration in rats and by intravenous infusion in dogs. The studies revealed that methemoglobinemia was the primary adverse effect in both species. Methemoglobin levels less than 40% were well tolerated in both species, while levels greater than 50% methemoglobin caused death in some rats. Additionally, a decrease in systemic BP was also observed with inhaled AIR001 exposure in dogs. These acute secondary and exaggerated pharmacological effects occurred daily throughout the 26-week treatment period. Chronic exposure did not alter the magnitude of either methemoglobinemia or hypotension or result in additional toxicity or compensatory responses. Based on the exposure levels that produced these pharmacodynamic responses in animals, relative to those measured in early clinical studies, it appears that an adequate margin of safety exists to support the continued clinical development of inhaled AIR001.

Clinical manifestations of food protein-induced enterocolitis syndrome.

PURPOSE OF REVIEW: To raise awareness among healthcare providers about the clinical and laboratory findings in acute and chronic food protein-induced enterocolitis syndrome (FPIES). RECENT FINDINGS: FPIES can be caused by trivial exposure or rare foods. SUMMARY: FPIES is a non-IgE-mediated reaction that usually presents with acute severe repetitive vomiting and diarrhea associated with lethargy, pallor, dehydration, and even hypovolemic shock. Manifestations resolve usually within 24-48 h of elimination of the causative food. In chronic cases, symptoms may include persistent diarrhea, poor weight gain, failure to thrive, and improvement may take several days after the food elimination. In the acute cases, laboratory evaluation may reveal thrombocytosis and neutrophilia, peaking about 6 h postingestion. Depending on the severity, metabolic acidosis and methemoglobinemia may occur. In chronic cases, anemia, hypoalbuminemia and eosinophilia may be seen. Radiologic evaluation or other procedures, such as endoscopy and gastric juice analysis may show nonspecific abnormal findings. The diagnosis is based on clinical manifestations. Further studies looking at the phenotypes of FPIES are needed to identify clinical subtypes, and to understand the predisposing factors for developing FPIES compared with immediate-type, IgE-mediated gastroenteropathies.

Neurometabolic disorder with microcephaly, dystonia, and central cyanosis masquerading as cerebral palsy.

Many neurodegenerative diseases can be misdiagnosed as cerebral palsy. The correct diagnosis is reached when the condition recurs in families or when there are specific clinical signs. The clinical and imaging features of 3 children, from 2 unrelated families, presenting with global developmental delay and dystonia are described, in whom the presence of cyanosis and methemoglobinemia confirmed the diagnosis of recessive hereditary methemoglobinemia type 2. Magnetic resonance imaging showed significant cerebellar atrophy in 2 of the 3 babies. In dark-skinned children, this condition is underdiagnosed, as mild cyanosis is difficult to detect. Screening for methemoglobinemia in children with dystonia, microcephaly, and progressive cerebellar atrophy can be helpful in identifying more cases. As there is no curative treatment for this autosomal recessive condition, the exact diagnosis offers the best chance for prenatal screening, by detecting deficient NADH--cytochrome b5 reductase enzyme activity or by identifying the specific mutation in cultured amniotic fluid cells.

A case of sodium chlorite toxicity managed with concurrent renal replacement therapy and red cell exchange.

INTRODUCTION: Sodium chlorite is a powerful oxidizing agent with multiple commercial applications. We report the presentation and management of a single case of human toxicity of sodium chlorite. CASE REPORT: A 65-year-old man presented to hospital after accidentally ingesting a small amount of a sodium chlorite solution. His principal manifestations were mild methemoglobinemia, severe oxidative hemolysis, disseminated intravascular coagulation, and anuric acute kidney injury. He was managed with intermittent hemodialysis, followed by continuous venovenous hemofiltration for management of acute kidney injury and in an effort to remove free plasma chlorite. Concurrently, he underwent two red cell exchanges, as well as a plasma exchange, to reduce the burden of red cells affected by chlorite. These interventions resulted in the cessation of hemolysis with stabilization of serum hemoglobin and platelets. The patient survived and subsequently recovered normal renal function. DISCUSSION: This is only the second case of sodium chlorite intoxication reported in the medical literature and the first to report the use of renal replacement therapy in combination with red cell exchange in its management.

Methemoglobinemia and ascorbate deficiency in hemoglobin E ß thalassemia: metabolic and clinical implications.

During investigations of the phenotypic diversity of hemoglobin (Hb) E ß thalassemia, a patient was encountered with persistently high levels of methemoglobin associated with a left-shift in the oxygen dissociation curve, profound ascorbate deficiency, and clinical features of scurvy; these abnormalities were corrected by treatment with vitamin C. Studies of erythropoietin production before and after treatment suggested that, as in an ascorbate-deficient murine model, the human hypoxia induction factor pathway is not totally dependent on ascorbate levels. A follow-up study of 45 patients with HbE ß thalassemia showed that methemoglobin levels were significantly increased and that there was also a significant reduction in plasma ascorbate levels. Haptoglobin levels were significantly reduced, and the high frequency of the 2.2 haptoglobin genotype may place an additional pressure on ascorbate as a free-radical scavenger in this population. There was, in addition, a highly significant correlation between methemoglobin levels, splenectomy, and factors that modify the degree of globin-chain imbalance. Because methemoglobin levels are modified by several mechanisms and may play a role in both adaptation to anemia and vascular damage, there is a strong case for its further study in other forms of thalassemia and sickle-cell anemia, particularly when splenic function is defective.

Toxicology and carcinogenesis studies of methylene blue trihydrate (Cas No. 7220-79-3) in F344/N rats and B6C3F1 mice (gavage studies).

UNLABELLED: Methylene blue trihydrate has a variety of biomedical and biologically therapeutic applications. Methylene blue trihydrate was nominated by the National Cancer Institute (NCI) for carcinogenicity testing based on the numerous uses of this compound and the lack of long-term toxicity data, including epidemiological studies of methylene blue trihydrate, as well as the inadequate animal data on this compound. Male and female F344/N rats and B6C3F1 mice were administered methylene blue trihydrate in 0.5% aqueous methylcellulose by gavage for 1 month, 3 months, or 2 years. Genetic toxicology studies were conducted using Salmonella typhimurium, Escherichia coli, cultured Chinese hamster ovary cells, mouse bone marrow cells, and mouse peripheral blood erythrocytes. 1-MONTH STUDY IN RATS: Groups of 10 male and 10 female core study rats and groups of 10 male and 10 female clinical pathology study rats were administered methylene blue trihydrate in 0.5% aqueous methylcellulose solution by gavage at doses of 0, 125, 250, 500, 1,000, or 2,000 mg/kg, 5 days per week for 5 weeks. In the 500 mg/kg groups, one male died the first week of the study and one male and four females died the second week of the study. All rats in the 1,000 mg/kg group died by study day 10, and all rats in the 2,000 mg/kg group died by study day 6. Final mean body weights of male and female rats in the 250 and 500 mg/kg groups were significantly less than those of the vehicle controls. Dosed rats developed methemoglobinemia and a regenerative Heinz body anemia. Significant increases in spleen weights occurred in all surviving dosed groups. There were also significant decreases in the thymus weights of 250 and 500 mg/kg males and 125 and 250 mg/kg females. Spleen lesions associated with methylene blue trihydrate administration included hematopoietic cell proliferation, pigmentation, lymphoid depletion of the lymphoid follicles, and capsular fibrosis. Hyperplasia of the bone marrow occurred in all dosed groups of rats. Liver lesions associated with methylene blue exposure included centrilobular necrosis in rats dying early, hematopoietic cell proliferation, and Kupffer cell pigmentation with erythrophagocytosis. 1-MONTH STUDY IN MICE: Groups of 10 male and 10 female core study mice were administered methylene blue trihydrate in 0.5% aqueous methylcellulose solution by gavage at doses of 0, 125, 250, 500, 1,000, or 2,000 mg/kg, 5 days per week for 5 weeks. None of the mice in the 500, 1,000, and 2,000 mg/kg groups survived to the end of the study. In the 250 mg/kg groups, two females died on days 16 and 18 and two males died on days 6 and 13. Mean body weights of surviving dosed mice were similar to those of the vehicle controls. Thinness, abnormal respiration, hypothermia, lethargy, ataxia, and ruffled fur were observed in a few surviving animals in the 250 mg/kg groups. Hypothermia and abnormal posture were observed in mice in the 500, 1,000, and 2,000 mg/kg groups. Dosed mice developed methemoglobinemia and a regenerative Heinz body anemia. Significant increases in spleen weights occurred in all surviving dosed groups of mice compared to vehicle controls. Significant decreases occurred in the thymus weights of 250 mg/kg males and females. The heart weights of 125 and 250 mg/kg females were significantly increased. Lesions in the spleen associated with methylene blue trihydrate administration included hematopoietic cell proliferation, pigmentation, and congestion. Liver lesions associated with methylene blue trihydrate administration included periportal degeneration, hematopoietic cell proliferation, and Kupffer cell pigmentation with erythrophagocytosis. The incidences of bone marrow pigmentation were significantly increased in all dosed groups of mice. Forestomach lesions that were related to methylene blue trihydrate administration included focal ulcer, inflammation, and squamous hyperplasia. 3-MONTH STUDY IN RATS: Groups of 10 male and 10 female core study rats and groups of 20 male and 20 female clinical pathology study rats were administered methylene blue trihydrate in 0.5% aqueous methylcellulose solution by gavage at doses of 0, 25, 50, 100 or 200 mg/kg, 5 days per week for 14 weeks. Mean body weights of males in the 200 mg/kg group were significantly less than those of the vehicle controls. Dosed rats developed methemoglobinemia and a regenerative Heinz body anemia. Significant increases in spleen weights occurred in males and females administered 50 mg/kg or greater. Thymus and lung weights of 50, 100, and 200 mg/kg males (except relative lung weight at 100 mg/kg) were significantly less than those of the vehicle controls. Spleen lesions in dosed rats included hematopoietic cell proliferation, congestion, lymphoid depletion of the lymphoid follicles, and capsular fibrosis. The incidences of bone marrow hyperplasia were significantly increased in groups administered 50 mg/kg or greater. There were no consistent effects of methylene blue trihydrate administration on reproductive system measures in male or female rats. 3-MONTH STUDY IN MICE: Groups of 10 male and 10 female core study mice and groups of 20 male and 20 female clinical pathology study mice were administered methylene blue trihydrate in 0.5% aqueous methylcellulose solution by gavage at doses of 0, 25, 50, 100, or 200 mg/kg, 5 days per week for 14 weeks. Mean body weights of all dosed groups were similar to or only slightly less than those of the vehicle control groups. Dosed mice developed methemoglobinemia and a regenerative Heinz body anemia. Spleen weights of 100 and 200 mg/kg males and 50 mg/kg or greater females were significantly greater than those of the vehicle control groups. Heart weights were significantly increased in 200 mg/kg males. In females, there were significant decreases in thymus weights at 50 mg/kg or greater. Males had decreased sperm motility and increased epididymal sperm counts at 200 mg/kg. In all dosed groups, the incidences of hematopoietic cell proliferation and pigmentation in the spleen were significantly greater than those in the vehicle controls. In the liver, the incidences of hematopoietic cell proliferation were significantly increased in males and females in the 100 and 200 mg/kg groups, and the incidences of Kupffer cell pigmentation were significantly increased in groups administered 50 mg/kg or greater. The incidences of bone marrow pigmentation were significantly increased in all dosed groups of mice except 25 mg/kg females. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were administered methylene blue trihydrate in 0.5% aqueous methylcellulose solution by gavage at doses of 0, 5, 25, or 50 mg/kg, 5 days per week for 2 years. Additional groups of 10 male and 10 female rats were administered the same doses for up to 18 months and were evaluated at 2 weeks and 3, 12, and 18 months for hematology. Survival of all dosed groups of rats was similar to that of the vehicle controls. Mean body weights of 25 and 50 mg/kg male rats were less than those of the vehicle controls after weeks 29 and 21, respectively. In the 25 and 50 mg/kg females, mean body weights were less after weeks 73 and 53. Dosed male and female rats developed methemoglobinemia, and females developed a regenerative Heinz body anemia. The incidences of pancreatic islet cell adenoma and adenoma or carcinoma (combined) were increased in all dosed groups of males, were significantly increased in 25 mg/kg males, and exceeded the historical range in controls (all routes). The incidence of pancreatic islet cell hyperplasia was significantly increased in the 50 mg/kg males. In the spleen, the incidence of hematopoietic cell proliferation in 50 mg/kg males was significantly increased; the incidences of capsular fibrosis were significantly increased in all dosed groups of males and in 5 and 50 mg/kg females. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were administered methylene blue trihydrate in a 0.5% aqueous methylcellulose solution by gavage at doses of 0, 2.5, 12.5, or 25 mg/kg, 5 days per week for 2 years. Additional groups of 30 male and 30 female mice were administered the same doses for up to 18 months and were evaluated at 2 weeks and 3, 12, or 18 months for hematology. Survival of dosed male and female groups exceeded that of the vehicle controls in a generally dose-related manner. Mean body weights of dosed female mice began to increase after weeks 29, 61, and 85, reaching final values that were 113%, 111%, and 106% of vehicle controls for the 2.5, 12.5, and 25 mg/kg groups, respectively. Dosed mice developed methemoglobinemia and a regenerative Heinz body anemia. The incidences of carcinoma and of adenoma or carcinoma (combined) of the small intestine occurred with a positive trend in males. The incidences of malignant lymphoma occurred with a positive trend in females, and the incidence in 25 mg/kg males exceeded the historical control range. The incidences of hematopoietic cell proliferation of the spleen were significantly increased in 12.5 and 25 mg/kg males and in 25 mg/kg females. The incidences of inflammation of the nose were significantly increased in 12.5 and 25 mg/kg females. GENETIC TOXICOLOGY: Methylene blue trihydrate was mutagenic in Salmonella typhimurium strains TA98 and TA100 with and without rat or hamster liver S9 activation enzymes; mutagenicity was also observed in Escherichia coli strain WP2 uvrA/pKM101 with and without rat liver S9. In cytogenetic tests with cultured Chinese hamster ovary cells, methylene blue trihydrate induced sister chromatid exchanges and chromosomal aberrations with and without S9. (ABSTRACT TRUNCATED).

Methemoglobinemia due to malachite green ingestion in a child.

Malachite green is a commercially available dye used to treat parasitic and fungal disease in fish. No previous reports of human injury could be located from acute ingestion of malachite green. We report a case of methemoglobinemia of 51% in a 3 year old girl after acute ingestion of malachite green from a commercially available aquarium product.