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THE CHEMICAL ENVIRONMENT
Methyl 2-cyanoacrylate (I) is used widely as an adhesive in the bonding of industrial materials and extensive experimentation has been carried out to investigate its potential • use as a biologically degradable adhesive in tissue repair and other surgical applications (Cited in F.C.T. 1969, 7, 75). This paper describes a method of analysis devised to correlate odour thresholds and sensory reactions to various concentrations of I. A simulated workbench exposure was created in which concentrations of 1-60 ppm were produced and the monomer or polymer vapour was collected in 0.5 N-sodium hydroxide, with subsequent liberation of formaldehyde. This was measured by a colorimetric method using chromotropic acid reagent• In the 14 subjects tested, the odour was first detectable at levels between 1 and 3 ppm, with initial nose irritation occurring at about 3 ppm and eye irritation at 5 ppm. Concentrations of 20 ppm or more caused lachrymation and rhinorrhoea, and at 60 ppm delayed but transient visual effects were seen in two subjects. It is suggested that atmospheric concentrations of I should be limited to 3 ppm to reduce he hazards from exposure.
1847. Dibutylaminoethanol--A small hazard Cornish, H. H., Dambrauskas, T. & Beatty, L. D. (1968)• Oral and inhalation toxicity of 2-N-dibutylaminoethanol. Am. ind. Hyg. Ass. J. 30, 46. The dibutylaminoethanol (DBAE) used in this study is one of a series of 2-N-alkylsubstituted aminoethanols which find possible application as curing and flotation agents, dispersants and emulsifiers in cosmetics, shampoos, waxes, polishes, lubricants and resins. Neutralized DBAE given to rats in the drinking water at concentrations resulting in an intake of 0.43 or 0.20 g/kg/day by males and 0-33 or 0.24 g/kg/day by females, caused an initial weight loss, which was never completely overcome, although subsequent growth rates were comparable in all groups. No such effect occurred in males ingesting 0.13 or females ingesting 0.14 g/kg/day. Changes found at necropsy included elevated kidney weights relative to body weight in the groups receiving the two higher dose levels, but there were no pathological changes in the kidney• Animals that died after acute oral doses of 4-8 g DBAE/ kg convulsed. Those that survived for a few hours, however, usually recovered• The oral LDso was 1.75 g/kg. Repeated doses were not cumulative• Inhalation exposure to 70 ppm DBAE for 6 hr daily for 5 days killed one out of five rats, while a concentration of 30 ppm reduced the growth rate but caused no deaths• Exposure to 22 ppm DBAE for 6 months produced no differences between test and control animals. At 70 ppm, DBAE caused eye and nose irritation, tremors and convulsions, but no signs of histological damage. The conclusion to be drawn from this study is that DBAE, with a boiling point of 225229°C and a low vapour pressure, is unlikely to be hazardous if handled in small amounts at room temperature. At higher temperatures, or with large surface areas exposed for volatilization, its nauseating odour should be a built-in safeguard•
1848. Citrate combats ethylene glycol poisoning Vaille, C., Debray, C., Souchard, M. & Roz~, C. (1968). Influence des citrates sur la lithiase r6nale b. l'6thyl6ne-glycol. Annls pharm, fr. 26, 593. In male rats ethylene glycol (I) is metabolized to calcium oxalate which is deposited as crystals in the kidneys (Cited in F.C.T. 1966, 4, 111) but such kidney stones are comparatively rare in females of the species. The effect is suppressed in males by ethanol, which is
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thought to compete as substrate for the oxidative enzymes responsible for the conversion of I to oxalate (ibid 1966, 4, 355). Phenacetin has also been shown to counteract some of the effects of I (ibid 1965, 3, 657). As citrate (II) plays an important part in calcium metabolism, and as the production and oxidation of II in the blood is increased by oestrogens, the effect of II on poisoning by I has been investigated. Two groups of ten male rats received I at a level of 1 ~o in their drinking water for 3 wk. The diet in one of these groups was supplemented with II at an estimated level of 2.5 g/rat/ day. A third group received II but not I. Either I or II given alone caused a loss of body weight, but the effect of II was the less severe and was attributed to a change in the calorie balance of the diet, since it eventually evened out. I and II given together did not have an additive effect, the weight loss being no greater than that with either compound given alone. The weights of spleen, adrenals and heart were not affected. Kidney weight was increased by I but unaffected by I and II or by I[ alone. Liver weight was decreased by I and also by I and II and by II alone. Blood urea was considerably increased by I, but with II alone or with I and II, normal values were obtained, confirming a strong interaction of I with II in the kidney. Serum proteins were unaltered. On histological examination of the kidneys, all rats treated with I alone were found to have lithiasis and tubular nephritis, while among the ten given I and II only four showed lithiasis, a much less severe incidence. In two of these four there was also slight tubular dilatation and epithelial atrophy. No other rats demonstrated changes in the kidneys and the other organs examined were normal in all the animals. The experiment clearly shows that II has a protective effect against the calcium oxalate precipitation and tubular nephritis induced by I. In a discussion of the possible mechanisms of this effect, it is suggested that II greatly increases the need for coenzymes in the Krebs cycle, either in the intestine or liver or both, so that I is largely eliminated without being converted to oxalate. On the basis of these findings the authors recommend the use of large oral doses of II in the treatment of acute poisoning by I. 1849. Go easy on paracetamol Boyd, E. M. & Hogan, Susan E. (1968). The chronic oral toxicity of paracetamol at the range of the LDso tloo dars~ in albino rats. Can. J. Physiol. Pharmac. 46, 239. Paracetamol (p-hydroxyacetanilide; I) in aqueous suspension was given to rats by intragastric intubation on 5 days/wk until 60 ~o of the animals had died or for 100 days, whichever occurred first. Daily doses ranged from 0.5 to 4 g/kg. The resultant LDso cloo days~was 0.77 g/kg/day. The maximal LDo t~oo a~rs) was estimated to be 0.4 g/kg/day and the minimal LDloo ~Ioo a~r~) 1"1 g/kg/day. Toxic signs produced by sublethal doses included hyperreflexia, aciduria, hypertrophy of the cardiac stomach and liver, atrophy of the testes, minor liver necrosis and nephritis and an increased susceptibility to infection. At the LDso level, I caused listlessness, pallor, inhibition of growth, diuresis, aciduria, testicular atrophy, hepatic necrosis, nephritis, dehydration and a capillary congestion of many organs. At and above the LD~oo level, anorexia, loss of body heat, weakening of reflexes, prostration and degenerative changes in several organs were additional effects of I. One interesting feature was the appearance of a minor abstinence syndrome when I was abruptly withdrawn from the 100-day survivors. Apart from the testicular atrophy, recovery occurred in 2 wk after withdrawal. By way of comment on the relevance of these results to human abuse of I, the authors