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2260. Methacrylate through the glove barrier
THE CHEMICAL ENVIRONMENT
915
boric acid. The situation was put more clearly in earlier surveys (ibm 1963, 1, 249; ibid 1965, 3, 99), which stated that in all reported cases of intoxication and deaths in infants arising from skin application, the preparation used was a boric acid solution or pure boric acid. Save for one suspected case (ibm 1967 5, 590), there is no evidence associating the use of borated talc with ill-health. Moreover, the inability of 5~o borated talc to penetrate intact skin or skin affected by nappy rash further testifies to the product's safety (ibid 1963, 1, 250). Even the British Medical Association's scathing attack on the unnecessary risk associated with therapeutically-used boric acid preparations could find no objection to the application of 5% borated talc to the skin of babies and infants provided the skin surface was unbroken (British Medical Journal 1966, ii, 233). The study by Nielsen (cited above) describes the importance of the vehicle and the size of the treated area in determining the extent of percutaneous absorption of three boric acid-containing preparations (pH 5.0--6.6) in rats. One preparation was a 2.5% aqueous boric acid jelly (BAJ) and the others were 2.8% boric acid/borate fatty ointments (BAFO), the boric acid in one case being complexed to polyvalent alcohols. When BAJ or either of the BAFO preparations was applied in 2-ml doses to intact skin (28 cm 2 in area) the urinary level of boron over 8 hr remained virtually unchanged, but when the preparations were applied to a similar area of severely damaged skin, urinary excretion of boron increased from 13 to 454 tzg/ml in the BAJ group and from 10 to 45 and 89/~g/ml in the two BAFO groups. Differences between the aqueous preparation and one fatty ointment were also seen following application of 1 ml to an enclosed area (4.3 cm 2) of severely-damaged skin. Urinary levels of boron rose from 4 to 173/~g/ml and from 5 to 11/zg/ml in the BAJ and BAFO groups, respectively. In the former group some 75% of the boric acid applied was absorbed but only one-third of that absorbed was excreted in the urine over 5 hr. In the latter group only 2% of the boric acid applied was absorbed and this was readily excreted. Thus the presence of the fatty ointment suppressed the absorption of boric acid through damaged skin, while with the aqueous preparation the rate of absorption apparently exceeded the capacity for immediate excretion in the urine. [This study in rats emphasizes the importance of the nature of the vehicle and condition of the skin in determining the extent of boric acid absorption, upon which the preparation's ultimate toxicity will depend.]
2260. Methacrylate through the glove barrier Pegum, J. S. & Medhurst, F. A. (1971). Contact dermatitis from penetration of rubber gloves by acrylic monomer. Br. reed. J. 2, 141. Methyl methacrylate monomer (I) has been shown in long-term animal experiments to have a relatively low level of oral toxicity (Cited in F.C.T. 1964, 2, 503). Besides being used in the preparation of polymers intended for food-contact applications, I has also been used extensively by orthopaedic surgeons in bone cements, which are prepared shortly before insertion into the bone by mixing a liquid consisting of I stabilized with ascorbic acid and containing dimethyl-p-toluidine as catalyst with a powder of polymethylmethacrylate granules and a benzoyl peroxide (II) activator. The paper cited above describes the case of a surgeon who on two occasions developed a rash on the palm of the left hand and the tips of the index and little fingers of the right hand after moulding the cement and introducing it into the bone cavity. Patch tests showed that he was sensitive to I and to II, but not to the other components of the cement. Experiments on fingers cut from rubber gloves demonstrated that I can diffuse through surgeons' gloves,
916
THE CHEMICAL ENVIRONMENT
possibly carrying solutes such as II with it. However, the diffusion of I apparently failed to damage the gloves sufficiently to make them permeable to bacteria, at least under laboratory conditions. The findings suggest that some cases of 'rubber glove dermatitis' may in fact have been attributable to some solvent able to penetrate the rubber and reach the skin. [Although the dermatitis in this instance was put down to the monomer, the possibility that benzoyl peroxide, a known sensitizer (Cited h7 F.C.T. 1971,9, 742), might in some cases be of more than marginal importance cannot be excluded.] 2261. More toxicity studies of organotin derivatives Pelikan, Z. & (~ern2~, E. (1970). The toxic effects of some di- and mono-N-octyl-tin compounds on white mice. Arch. Tox. 26, 196. Pelikan, Z. & (~ern2~, E. (1970). Toxic effects of some "mono-N-butyl-tin compounds" on white mice. Arch. Tox. 27, 79. Research into the toxicity of organotin derivatives has expanded with the recent extension of their industrial and agricultural applications. Triphenyltin has shown an immunosuppressive effect (Cited in F.C.T. 1970, 8, 709), and trialkyltin compounds are potent inhibitors of oxidative phosphorylation in mitochondria (ibid 1971, 9, 159). The authors of the papers cited above have described the effect of bis(tri-n-butyltin)oxide on the skin of rats and the eyes of rabbits (ibid 1969, 7, 694; ibid 1970, 8, 604), and they have also studied some dialkyltin compounds and have demonstrated fatty degeneration in the hepatocytes of mice given oral doses of di-n-octyltin derivatives (Pelikan et al. Fd Cosmet. Toxicol. 1970, 8, 655). The two papers cited above describe further studies on the dialkyltins, together with some effects of monoalkyltin derivatives under comparable conditions. The first deals with the effects of a single dose of di-n-octyltin-bis-(2-ethylhexyl mercaptoacetate) (I), di-noctyltin-bis(dodecylmercaptide) (II), di-n-octyltin-bis(butyl mercaptoacetate) (III) or monon-octyltin-tris-(2-ethylhexyl mercaptoacetate) (IV) on white mice. In a dose of 4 g/kg, none of these compounds had any effect after 4 hr. After 12 hr some mice, especially those receiving I or III or to a lesser extent IV, became weak and exhausted, with laboured respiration. Reactions to light, sound and mechanical stimuli remained normal. Only those animals given II showed no effects at this stage. After 24 hr, most mice given I, III or IV clearly showed toxic signs, notably inactivity, anorexia and an ability to respond only to strong mechanical stimuli. Breathing was shallow and periodic. A few mice given III had tonic-clonic convulsions. Those given II showed similar but less marked reactions. Mice given III or IV generally died between 24 and 26 hr after treatment. Autopsy findings after treatment with I were ischaemia of the stomach walls, with minor haemorrhages, distension of the stomach with gas, and hyperaemia of the intestinal walls. The liver was light red, enlarged and soft. The gall-bladder was swollen. The kidneys were red but not swollen. Compound IV had similar effects, and the effects of III were qualitatively similar but more intense. Compound II caused considerable engorgement of the stomach with liquid and gas, with hyperaemia of both stomach and intestinal walls. The liver was reddish, soft and slightly enlarged, the spleen hyperaemic and enlarged. No change appeared in the kidneys. All the compounds tested produced fatty degeneration in the hepatocytes, most obviously in the peripheral zones of the liver. The second paper cited deals with the effects on white mice of mono-n-butyltin trichloride (V), mono-n-butyltin acid (VI), mono-n-butylthiotin acid (VII) or mono-n-butyltin tris(2-ethylhexyl mercaptoacetate) (VIII) in a dose of 4 g/kg in each case. After 4 hr there were
915
boric acid. The situation was put more clearly in earlier surveys (ibm 1963, 1, 249; ibid 1965, 3, 99), which stated that in all reported cases of intoxication and deaths in infants arising from skin application, the preparation used was a boric acid solution or pure boric acid. Save for one suspected case (ibm 1967 5, 590), there is no evidence associating the use of borated talc with ill-health. Moreover, the inability of 5~o borated talc to penetrate intact skin or skin affected by nappy rash further testifies to the product's safety (ibid 1963, 1, 250). Even the British Medical Association's scathing attack on the unnecessary risk associated with therapeutically-used boric acid preparations could find no objection to the application of 5% borated talc to the skin of babies and infants provided the skin surface was unbroken (British Medical Journal 1966, ii, 233). The study by Nielsen (cited above) describes the importance of the vehicle and the size of the treated area in determining the extent of percutaneous absorption of three boric acid-containing preparations (pH 5.0--6.6) in rats. One preparation was a 2.5% aqueous boric acid jelly (BAJ) and the others were 2.8% boric acid/borate fatty ointments (BAFO), the boric acid in one case being complexed to polyvalent alcohols. When BAJ or either of the BAFO preparations was applied in 2-ml doses to intact skin (28 cm 2 in area) the urinary level of boron over 8 hr remained virtually unchanged, but when the preparations were applied to a similar area of severely damaged skin, urinary excretion of boron increased from 13 to 454 tzg/ml in the BAJ group and from 10 to 45 and 89/~g/ml in the two BAFO groups. Differences between the aqueous preparation and one fatty ointment were also seen following application of 1 ml to an enclosed area (4.3 cm 2) of severely-damaged skin. Urinary levels of boron rose from 4 to 173/~g/ml and from 5 to 11/zg/ml in the BAJ and BAFO groups, respectively. In the former group some 75% of the boric acid applied was absorbed but only one-third of that absorbed was excreted in the urine over 5 hr. In the latter group only 2% of the boric acid applied was absorbed and this was readily excreted. Thus the presence of the fatty ointment suppressed the absorption of boric acid through damaged skin, while with the aqueous preparation the rate of absorption apparently exceeded the capacity for immediate excretion in the urine. [This study in rats emphasizes the importance of the nature of the vehicle and condition of the skin in determining the extent of boric acid absorption, upon which the preparation's ultimate toxicity will depend.]
2260. Methacrylate through the glove barrier Pegum, J. S. & Medhurst, F. A. (1971). Contact dermatitis from penetration of rubber gloves by acrylic monomer. Br. reed. J. 2, 141. Methyl methacrylate monomer (I) has been shown in long-term animal experiments to have a relatively low level of oral toxicity (Cited in F.C.T. 1964, 2, 503). Besides being used in the preparation of polymers intended for food-contact applications, I has also been used extensively by orthopaedic surgeons in bone cements, which are prepared shortly before insertion into the bone by mixing a liquid consisting of I stabilized with ascorbic acid and containing dimethyl-p-toluidine as catalyst with a powder of polymethylmethacrylate granules and a benzoyl peroxide (II) activator. The paper cited above describes the case of a surgeon who on two occasions developed a rash on the palm of the left hand and the tips of the index and little fingers of the right hand after moulding the cement and introducing it into the bone cavity. Patch tests showed that he was sensitive to I and to II, but not to the other components of the cement. Experiments on fingers cut from rubber gloves demonstrated that I can diffuse through surgeons' gloves,
916
THE CHEMICAL ENVIRONMENT
possibly carrying solutes such as II with it. However, the diffusion of I apparently failed to damage the gloves sufficiently to make them permeable to bacteria, at least under laboratory conditions. The findings suggest that some cases of 'rubber glove dermatitis' may in fact have been attributable to some solvent able to penetrate the rubber and reach the skin. [Although the dermatitis in this instance was put down to the monomer, the possibility that benzoyl peroxide, a known sensitizer (Cited h7 F.C.T. 1971,9, 742), might in some cases be of more than marginal importance cannot be excluded.] 2261. More toxicity studies of organotin derivatives Pelikan, Z. & (~ern2~, E. (1970). The toxic effects of some di- and mono-N-octyl-tin compounds on white mice. Arch. Tox. 26, 196. Pelikan, Z. & (~ern2~, E. (1970). Toxic effects of some "mono-N-butyl-tin compounds" on white mice. Arch. Tox. 27, 79. Research into the toxicity of organotin derivatives has expanded with the recent extension of their industrial and agricultural applications. Triphenyltin has shown an immunosuppressive effect (Cited in F.C.T. 1970, 8, 709), and trialkyltin compounds are potent inhibitors of oxidative phosphorylation in mitochondria (ibid 1971, 9, 159). The authors of the papers cited above have described the effect of bis(tri-n-butyltin)oxide on the skin of rats and the eyes of rabbits (ibid 1969, 7, 694; ibid 1970, 8, 604), and they have also studied some dialkyltin compounds and have demonstrated fatty degeneration in the hepatocytes of mice given oral doses of di-n-octyltin derivatives (Pelikan et al. Fd Cosmet. Toxicol. 1970, 8, 655). The two papers cited above describe further studies on the dialkyltins, together with some effects of monoalkyltin derivatives under comparable conditions. The first deals with the effects of a single dose of di-n-octyltin-bis-(2-ethylhexyl mercaptoacetate) (I), di-noctyltin-bis(dodecylmercaptide) (II), di-n-octyltin-bis(butyl mercaptoacetate) (III) or monon-octyltin-tris-(2-ethylhexyl mercaptoacetate) (IV) on white mice. In a dose of 4 g/kg, none of these compounds had any effect after 4 hr. After 12 hr some mice, especially those receiving I or III or to a lesser extent IV, became weak and exhausted, with laboured respiration. Reactions to light, sound and mechanical stimuli remained normal. Only those animals given II showed no effects at this stage. After 24 hr, most mice given I, III or IV clearly showed toxic signs, notably inactivity, anorexia and an ability to respond only to strong mechanical stimuli. Breathing was shallow and periodic. A few mice given III had tonic-clonic convulsions. Those given II showed similar but less marked reactions. Mice given III or IV generally died between 24 and 26 hr after treatment. Autopsy findings after treatment with I were ischaemia of the stomach walls, with minor haemorrhages, distension of the stomach with gas, and hyperaemia of the intestinal walls. The liver was light red, enlarged and soft. The gall-bladder was swollen. The kidneys were red but not swollen. Compound IV had similar effects, and the effects of III were qualitatively similar but more intense. Compound II caused considerable engorgement of the stomach with liquid and gas, with hyperaemia of both stomach and intestinal walls. The liver was reddish, soft and slightly enlarged, the spleen hyperaemic and enlarged. No change appeared in the kidneys. All the compounds tested produced fatty degeneration in the hepatocytes, most obviously in the peripheral zones of the liver. The second paper cited deals with the effects on white mice of mono-n-butyltin trichloride (V), mono-n-butyltin acid (VI), mono-n-butylthiotin acid (VII) or mono-n-butyltin tris(2-ethylhexyl mercaptoacetate) (VIII) in a dose of 4 g/kg in each case. After 4 hr there were