Derivation of the critical effect size/benchmark response for the dose-response analysis of the uptake of radioactive iodine in the human thyroid.

Potential adverse effects of chemical substances on thyroid function are usually examined by measuring serum levels of thyroid-related hormones. Instead, recent risk assessments for thyroid-active chemicals have focussed on iodine uptake inhibition, an upstream event that by itself is not necessarily adverse. Establishing the extent of uptake inhibition that can be considered de minimis, the chosen benchmark response (BMR), is therefore critical. The BMR values selected by two international advisory bodies were 5% and 50%, a difference that had correspondingly large impacts on the estimated risks and health-based guidance values that were established. Potential treatment-related inhibition of thyroidal iodine uptake is usually determined by comparing thyroidal uptake of radioactive iodine (RAIU) during treatment with a single pre-treatment RAIU value. In the present study it is demonstrated that the physiological intra-individual variation in iodine uptake is much larger than 5%. Consequently, in-treatment RAIU values, expressed as a percentage of the pre-treatment value, have an inherent variation, that needs to be considered when conducting dose-response analyses. Based on statistical and biological considerations, a BMR of 20% is proposed for benchmark dose analysis of human thyroidal iodine uptake data, to take the inherent variation in relative RAIU data into account. Implications for the tolerated daily intakes for perchlorate and chlorate, recently established by the European Food Safety Authority (EFSA), are discussed.

Orange-Pigmented Sputum as a Manifestation of Smoke Grenade Inhalation Injury.

A 34-year-old man presented with scanty hemoptysis, orange-colored expectoration, and mild dyspnea. He was in an enclosed building taking part in a military training exercise inhaling an orange-colored smoke from a smoke grenade ignition. His symptoms developed immediately after the initial exposure but he sought medical assistance 20 hours later because of their persistence. Fiberoptic bronchoscopy was performed revealing diffuse inflammatory tracheobronchial tree with streaky orange-pigmented secretions in the trachea and both main-stem bronchi. Acute tracheobronchitis was diagnosed and the patient was treated with nebulized bronchodilators and intravenous corticosteroids showing complete recovery. To our knowledge, this is the first well-documented report of inhalation injury induced by a smoke bomb explosion including potassium chlorate oxidizer and Sudan I and presenting with orange-pigmented sputum production. Smoke inhalation injury is associated with significant morbidity and mortality. The heterogeneity of the smoke and the large variety of the resulting symptoms may be the reason why a definition, specific diagnostic criteria, and therapeutic guidelines are still lacking.

New considerations on hydrogen peroxide and related substances as food additives in view of carcinogenicity.

The use of hydrogen peroxide as a labile and safe food preservative in fish cake and boiled noodles has recently been restricted by the Japanese government, since hyperplasia has been found in the duodenum of mice after long-term peroral study. The action of compounds with resembling mode of action, potassium bromate as an improving agent in bread, and sodium chlorate as a weed killer are discussed in this paper in view of developmental and environmental pharmacology.

Potential health effects of chlorine dioxide as a disinfectant in potable water supplies.

Chlorination of potable water supplies high in organics may yield carcinogenic compounds such as trihalomethanes. Chlorine dioxide has been proposed as an alternative disinfectant to chlorine. However, chlorine dioxide is a strong oxidant that forms significant amounts of chlorite when added to potable water supplies, and chlorite is similar to nitrite in its molecular structure and may be similar in its mechanism of methemoglobin production. Nitrites and chlorites are thought to act synergistically to produce MetHb. Neonates and persons with G-*-PD deficiency are likely to be unusually susceptible to MetHb formation from these compounds because their red cells lack the metabolic machinery to adequately protect against oxidant stress. Since male blacks represent the largest population in the U.S. to be G-6PD deficient, Black male neonates may represent the group at highest risk to the use of chlorine dioxide as a disinfectant in the nations water supplies.