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The present study suggests that, while the neurotoxic effects of MDMA on 5-HT neurons in the human cortex may be reversible, the effects of MDMA on memory function may be long-lasting.

The combination of alcohol and cocaine is popular among drug users, perhaps because of more intense feelings of 'high' beyond that perceived with either drug alone, less intense feelings of alcohol-induced inebriation and tempering of discomfort when coming down from a cocaine 'high'. A review is presented of the medical literature on psychological and somatic effects and consequences of combined use of alcohol and cocaine in man. The search was carried out with Medline, the Science Citation Index/Web of Science and Toxline. Exclusion and inclusion criteria for this search are identified. There is generally no evidence that the combination of the two drugs does more than enhance additively the already strong tendency of each drug to induce a variety of physical and psychological disorders. A few exceptions must be noted. Cocaine consistently antagonizes the learning deficits, psychomotor performance deficits and driving deficits induced by alcohol. The combination of alcohol and cocaine tends to have greater-than-additive effects on heart rate, concomitant with up to 30% increased blood cocaine levels. Both prospective and retrospective data further reveal that co-use leads to the formation of cocaethylene, which may potentiate the cardiotoxic effects of cocaine or alcohol alone. More importantly, retrospective data suggest that the combination can potentiate the tendency towards violent thoughts and threats, which may lead to an increase of violent behaviours.

Objectives-To estimate dermal absorption of vaporous and liquid 2-methoxyethanol (ME) and in volunteers. Methods-Five volunteers (two men and three women) were dermally exposed to vaporised and liquid ME and EE. Dermal exposure on an area of about 1000 cm2 (forearm and hand) to vapours ofME and EE (4000 mglm' ME and 3700 mglm' EE) lasted for 45 minutes. Duration of exposure to liquid ME and EE on an area of 27 cm2 (forearm) was 15 minutes. Dermal uptake was assessed by measurement of the main metabolites in urinary methoxyacetic acid (MAA) and ethoxyacetic acid (EAA). For each volunteer, excretion of metabolites was compared with a reference inhalatory exposure. Results-Mean (SD) absorption rates of ME and EE vapour were 36 (11) and 19 (6) cmlh respectively. The mean (SD) absorption rates of the liquid ME and EE amounted to 2-9 (2.0) and 0-7 (0.3) mglcm'.h. Conclusions-Vaporised and liquid ME and EE are readily absorbed through the skin. In the combined inhalatory and dermal exposure when whole body surface is exposed to vapour, the uptake through the skin is estimated to be 55% of the total uptake of ME and 42% of EE. Dermal uptake resulting from skin contact ofboth hands and forearms (about 2000 cm?) with liquid ME and EE for 60 minutes would exceed inhalatory uptake ofthe eight hour occupational exposure limit by 100 times at 16 mg/iM3 of ME and 20 times at 19 mg/mi of EE. The substantial skin uptake of ME and EE indicates that in assessing the health risks biological monitoring and use of biological exposure indices are preferable to environmental monitoring. (Occup Environ Med 1997;54:38-43) Keywords: 2-methoxyethanol; 2-ethoxyethanol, dermal exposure Although often comprising < 10% of the final product, 2-methoxyethanol (ME) and (4 7) hours.3The main concern for human exposure is the occupational environment. The occupational exposure limits (OEL) of ME and EE are set in The Netherlands5 and United States6 at 5 ppm (16 and 19 mg/M3, respectively). A skin notation assigned to ME and EE in these OEL documents implies that skin absorption might be an important route of entry.Despite hard evidence that both glycol ethers as liquids are readily absorbed through human skin in vitro7 there are few human data on skin absorption of ME and EE in the liquid as well as in the vapour phase. Human data for skin uptake of another glycol ether 2-butoxyethanol have been published,8 9 reporting that dermal exposure to 2-butoxyethanol, both liquid and vapour, was even more important than respiratory uptake. The purpose of this study was, therefore, to estimate the percutaneous absorption of ME and EE in volunteers under controlled experimental conditions. Subjects and methods SUBJECTSThe volunteers (two men and three women) ranged in age from 22 to 25. All were without a history of serious diseases and their skins appeared normal. None of them took medicines or alcohol from at least 12 hours before exposure until the end of collection of urine. The experimental protocol was submitted to and approved by the med...

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