Environmental toxicology and health effects associated with dinitrotoluene exposure.

Dinitrotoluenes (DNTs) are nitroaromatic compounds appearing as pale yellow crystalline solids at room temperature. Dinitrotoluenes exist as a mixture of 2 to 6 isomers, with 2,4-DNT, and 2,6-DNT being the most significant. About 500 persons are estimated to be potentially exposed yearly to 2,4-DNT and 2,6-DNT during the production of munitions and explosives. The main route of human exposure at ammunition facilities is inhalation, but dermal contact and inadvertent ingestion can also be substantial. In factory workers, exposure to DNTs has been linked to many adverse health effects, including cyanosis, vertigo, headache, metallic taste, dyspnea, weakness and lassitude, loss of appetite, nausea, and vomiting. Other symptoms including pain or parasthesia in extremities, abdominal discomfort, tremors, paralysis, chest pain, and unconsciousness have also been reported. The primary targets of DNT toxicity are the hematopoietic system (pallor, cyanosis, anemia, and leukocytosis), the cardiovascular system (ischemic heart disease), the nervous system (muscular weakness, headache, dizziness, nausea, insomnia, and tingling pains in the extremities) and the reproductive system (reduction of sperm counts, alteration of sperm morphology, and aspermatogenesis). An association between DNT exposure and increased risk of hepatocellular carcinomas and subcutaneous tumors in rats, as well as renal tumors in mice, has been established. Epidemiologic studies of DNT toxicity have been limited to small groups of workers who had been occupationally exposed at various ammunitions production facilities. Clearly defining the health effects of DNTs with a high degree of confidence has therefore been difficult because of the multigenic nature of occupational exposure. In an attempt to update the toxicologic profile of the DNTs, we hereby provide a critical review of the environmental and toxicologic pathology of DNTs, with a special emphasis on their potential implications for public health.

Astrocyte-endothelial interaction: physiology and pathology.

The blood-brain barrier of higher vertebrates is formed by the layer of endothelial cells lining the brain microvessels. The close anatomical association between endothelial cells and perivascular astrocytic end feet suggests cooperation between these cell types in forming and maintaining the blood-brain barrier. This review considers evidence from grafting experiments, developmental studies and culture models of the brain endothelium, concerning the inductive influences acting on the endothelium, and from endothelial cells acting on perivascular astrocytes. Examples from pathology and neurotoxicology which may involve breakdown of induction are also considered.

Functional/metabolic modulation of the brain stem lesions caused by 1,3-dinitrobenzene in the rat.

To determine whether neuronal activity plays a role in the localisation of brain stem lesions in 1,3-dinitrobenzene intoxication we produced asymmetrical changes in auditory input by rupturing the left tympanic membrane in Fischer rats. This raised the auditory threshold on that side from 57-63 dB to 104-122 dB. It also decreased glucose utilisation in the ipsilateral cochlear nucleus and significantly increased utilisation in the contralateral nucleus, resulting in a relative deficit of 72 +/- 6%. Similarly, tympanic membrane rupture led to decreased glucose utilisation in the contralateral and increased utilisation in the ipsilateral inferior colliculus. Additional exposure to "white noise" prevented the decrease in glucose utilisation in the contralateral inferior colliculus. Dosing with dinitrobenzene (10 mg/kg in 4 doses over 48 hr) to otherwise normal rats produces symmetrical vasculonecrotic lesions in these regions, but in animals with left tympanic membrane rupture the severity of morphological changes in the ipsilateral cochlear nucleus and the contralateral inferior colliculus were substantially reduced. Additional exposure to "white noise" increased the degree of damage in the ipsilateral cochlear nucleus and contralateral inferior colliculus. These findings indicate that altered auditory function in rats, with its associated metabolic consequences exercises a significant role in the development of brain stem damage in auditory pathways following dinitrobenzene intoxication.

Airborne pigmented contact dermatitis due to musk ambrette in incense.

We reported 2 patients with pigmented contact dermatitis caused by occupational airborne contactants, whitening dyes in clothes and formaldehyde in packing adhesive tapes. A women developed airborne pigmented contact dermatitis due to musk ambrette in incense. Patch testing confirmed the diagnosis. Since olden times, people in Japan have burnt incense when they worshipped their ancestors. Recently, it has been in fashion to enjoy perfumes and people may burn incense all day long every day. Our patient burnt 2 kinds of incense every day for about 5 years. We assumed musk ambrette was volatilized when incense was burnt, and contact on her face being dissolved in sebum, thus inducing allergic pigmented contact dermatitis.

Urinary catecholamine excretion and blood sugar response during acute poisonings with dinitrobenzenes.

Rats were injected intraperitoneally with 0.015 mmol of p-dinitrobenzene/kg, 0.15 mmol of m-dinitrobenzene/kg and 0.45 mmol of o-dinitrobenzene/kg body wt. The dinitrobenzenes induced methaemoglobin concentrations of 86%, 60% and 49%, respectively, as well as increases of urinary catecholamine excretion and blood sugar concentration. Due to hyperglycaemia the glycolysis may be stimulated as mechanism for energy production in methaemoglobin-induced oxygen deficiency and as mechanism for reduction of methaemoglobin, that means as responses favouring survival after poisoning.