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Sensitization to epoxy resin components
Occupational health-Fd
206
Cosmrr.
mutagenicity in the Salmo~lla typhirnuriurn TA 1535 method, with and without S-9 activation. The technical-grade sample produced a weak dose-related increase in the number of revertant cells at concentrations from 50 to 1600 pg/agar plate. Levels above 1600 pg/plate were toxic. The pure grade showed only a very slight sporadic increase in the numbers of revertants; it too was toxic at levels above 16OOpg/ plate. Distillation of technical-grade DBCP yielded an initial fraction rich in epichlorhydrin, and even at levels as low as 100 pg/plate this fraction produced more than twice the number of revertants produced by the highest concentration of technical DBCP tested. The response of the technical-grade DBCP in the dose-response tests correlated with the response that would be expected from the equivalent amount of pure epichlorhydrin. Activation of both grades of DBCP with S-9 derived from Aroclor-pretreated rats, however. resulted in similar strong dose-related mutagenic responses in the range 20--2OO/lg/plate. It is clear that epichlorhydrin contributes very significantly to the direct mutagenic activity of commercial samples of DBCP, but that DBCP itself is also potently mutagenic after metabolic activation in the liver. The slight direct activity of the ‘pure’ DBCP may be attributable to the compound itself or to traces of impurities. Sensitization
to epoxy
resin
components
Thorgeirsson. A. (1978). Sensitization capacity of epoxy reactive diluents in the guinea pig. Acra dermclever.,
Stock/z.
58, 329.
Thorgeirsson, A. (1978). Sensitization capacity of epoxy resin hardeners in the guinea pig. Acta derrnuener.,
Stockh.
58. 332.
Epoxy resins and their hardeners are commonly responsible for contact allergy (Cired iri F.C.T. 1974. 12, 582). There is evidence that sensitizing capacity may reside only in compounds of lowest molecular weight (ibid 1978, 16. 503) and diluents and hardeners may also play a part in sensitizing industrial handlers. In the first study cited above, five reactive diluents containing epoxide groups and with molecular weights between 175 and 360, and a sixth, an aliphatic polyglycidyl ether of molecular weight 1700, were tested in a guinea-pig maximization test. 1,2-Epoxydodecane elicited reactions in 407; of the animals, the monoglycidyl ester of synthetic fatty acids in 87’4, the monoglycidyl ether of isomeric alcohols in 80%, the diglycidyl ether of butanediol in 60%. and the diglycidyl ether of neopentylglycol in 87%. The highmolecular-weight polyglycidyl ether produced no reactions. In the second paper cited, the results of a guineapig maximization test on a number of epoxy resin hardeners are described. The hardeners included seven aliphatic polyamines, three cycloaliphatic polyamines, two polyaminoamides, an aromatic amine and adducts of phenol-accelerated triethylenetetramine (TETA). of TETA and propylene oxide, of isophoronediamine and low-molecular-weight epoxy resin, and of diethylenetriamine and epoxy resin. Reactivity to the aliphatic polyamines ranged from 55 to 93% and diaminodiphenyh-nethane elicited
‘Fo.vicol.
Vol. 18. no. 2
reactions in 2090. There was no reaction to one of the cycloaliphatic polyamines. 3,3’-dimethyl-4,4’diaminodicyclohexylmethane. but 100°,0 of the tested animals reacted to the other two. isophoronediamine and N-aminoethylpiperazine. A polyaminoamide based on tetraethylenepentamine elicited reactions in 673, of the animals but that based on TETA in only 20?*. The adduct of phenol-accelerated TETA produced reactions in 47:);. but there was no reaction to the other triethylenetetramine adducts. The adduct of isophoronediamine and a low-molecular-weight epoxy resin gave reactions in 737: of the animals. The results indicated that amine-free polyaminoamides are probably not sensitizers and that certain adducts, also, are not sensitizers unless they contain some free amine. In view of the sensitizing capacity of many of the diluents and hardeners tested in these studies, there is a need for further tests on these and other substances used in epoxy resins in order to identify. or if necessary develop. additional non-sensitizing compounds.
Combined
solvents+ffects
in rats
Vainio. H.. Savolainen, H. JL Pfaffli. P. (1978). Biochemical and toxicological effects of combined exposure to I.l.l-trichloroethane and trichloroethylene on rat liver and brain. .Yerlohiotica 8. 191. Trichloroethylene is a potentially toxic solvent, its harmful effects being attributed largely to its metabolite trichloroethanol (Cited in F.C.7: 1974. 12, 163); among the toxic effects produced are liver lesions (ibid 1978, 16, 491). Although I.l,l-trichloroethane is relatively innocuous (ibid 1975. 13, 402), it is apparently able to bind to cytochrome P-450 and so affect liver function (Pelkonen & Vainio, FEB.9 Letf. 1975, 51. I I). Industrial exposure to such solvents rarely involves a single compound, and the results of an investigation into the combined toxicity of these two chlorinated hydrocarbons are therefore of interest. Male rats were exposed to 500 ppm I, I.l-trichloroethane and 200 ppm trichloroethylene together in the atmosphere of a I m3 exposure chamber for 6 hr daily for 4 days. On day 5, two animals were killed immediately and two groups of four each were further exposed to the solvents for 2 hr or 6 hr before they were killed. Brain, liver, lung and perirenal fat samples were taken for estimation of the compounds. After 4 days, marked accumulation of trichloroethane was found in perirenal fat, but no trichloroethylene appeared there until the exposure on day 5. Brain retention of the two compounds was in the ratio 8:1 (l.I,I-trichloroethane:trichloroethylene), and a similar relative distribution occurred in lung tissue. In liver, the trichloroethylene concentration decreased towards the end of the experiment on the fifth day. The brain-protein content was not significantly altered by combined exposure, but in rats re-exposed on day 5 for 6 hr there was a reduction in brain RNA. Acid-proteinase activity was increased in rats after the 2-hr exposure on day 5 but was normal after the 6-hr exposure. Brain glutathione was not affected by the exposure. Microsomal drug-metabolizing activity in
206
Cosmrr.
mutagenicity in the Salmo~lla typhirnuriurn TA 1535 method, with and without S-9 activation. The technical-grade sample produced a weak dose-related increase in the number of revertant cells at concentrations from 50 to 1600 pg/agar plate. Levels above 1600 pg/plate were toxic. The pure grade showed only a very slight sporadic increase in the numbers of revertants; it too was toxic at levels above 16OOpg/ plate. Distillation of technical-grade DBCP yielded an initial fraction rich in epichlorhydrin, and even at levels as low as 100 pg/plate this fraction produced more than twice the number of revertants produced by the highest concentration of technical DBCP tested. The response of the technical-grade DBCP in the dose-response tests correlated with the response that would be expected from the equivalent amount of pure epichlorhydrin. Activation of both grades of DBCP with S-9 derived from Aroclor-pretreated rats, however. resulted in similar strong dose-related mutagenic responses in the range 20--2OO/lg/plate. It is clear that epichlorhydrin contributes very significantly to the direct mutagenic activity of commercial samples of DBCP, but that DBCP itself is also potently mutagenic after metabolic activation in the liver. The slight direct activity of the ‘pure’ DBCP may be attributable to the compound itself or to traces of impurities. Sensitization
to epoxy
resin
components
Thorgeirsson. A. (1978). Sensitization capacity of epoxy reactive diluents in the guinea pig. Acra dermclever.,
Stock/z.
58, 329.
Thorgeirsson, A. (1978). Sensitization capacity of epoxy resin hardeners in the guinea pig. Acta derrnuener.,
Stockh.
58. 332.
Epoxy resins and their hardeners are commonly responsible for contact allergy (Cired iri F.C.T. 1974. 12, 582). There is evidence that sensitizing capacity may reside only in compounds of lowest molecular weight (ibid 1978, 16. 503) and diluents and hardeners may also play a part in sensitizing industrial handlers. In the first study cited above, five reactive diluents containing epoxide groups and with molecular weights between 175 and 360, and a sixth, an aliphatic polyglycidyl ether of molecular weight 1700, were tested in a guinea-pig maximization test. 1,2-Epoxydodecane elicited reactions in 407; of the animals, the monoglycidyl ester of synthetic fatty acids in 87’4, the monoglycidyl ether of isomeric alcohols in 80%, the diglycidyl ether of butanediol in 60%. and the diglycidyl ether of neopentylglycol in 87%. The highmolecular-weight polyglycidyl ether produced no reactions. In the second paper cited, the results of a guineapig maximization test on a number of epoxy resin hardeners are described. The hardeners included seven aliphatic polyamines, three cycloaliphatic polyamines, two polyaminoamides, an aromatic amine and adducts of phenol-accelerated triethylenetetramine (TETA). of TETA and propylene oxide, of isophoronediamine and low-molecular-weight epoxy resin, and of diethylenetriamine and epoxy resin. Reactivity to the aliphatic polyamines ranged from 55 to 93% and diaminodiphenyh-nethane elicited
‘Fo.vicol.
Vol. 18. no. 2
reactions in 2090. There was no reaction to one of the cycloaliphatic polyamines. 3,3’-dimethyl-4,4’diaminodicyclohexylmethane. but 100°,0 of the tested animals reacted to the other two. isophoronediamine and N-aminoethylpiperazine. A polyaminoamide based on tetraethylenepentamine elicited reactions in 673, of the animals but that based on TETA in only 20?*. The adduct of phenol-accelerated TETA produced reactions in 47:);. but there was no reaction to the other triethylenetetramine adducts. The adduct of isophoronediamine and a low-molecular-weight epoxy resin gave reactions in 737: of the animals. The results indicated that amine-free polyaminoamides are probably not sensitizers and that certain adducts, also, are not sensitizers unless they contain some free amine. In view of the sensitizing capacity of many of the diluents and hardeners tested in these studies, there is a need for further tests on these and other substances used in epoxy resins in order to identify. or if necessary develop. additional non-sensitizing compounds.
Combined
solvents+ffects
in rats
Vainio. H.. Savolainen, H. JL Pfaffli. P. (1978). Biochemical and toxicological effects of combined exposure to I.l.l-trichloroethane and trichloroethylene on rat liver and brain. .Yerlohiotica 8. 191. Trichloroethylene is a potentially toxic solvent, its harmful effects being attributed largely to its metabolite trichloroethanol (Cited in F.C.7: 1974. 12, 163); among the toxic effects produced are liver lesions (ibid 1978, 16, 491). Although I.l,l-trichloroethane is relatively innocuous (ibid 1975. 13, 402), it is apparently able to bind to cytochrome P-450 and so affect liver function (Pelkonen & Vainio, FEB.9 Letf. 1975, 51. I I). Industrial exposure to such solvents rarely involves a single compound, and the results of an investigation into the combined toxicity of these two chlorinated hydrocarbons are therefore of interest. Male rats were exposed to 500 ppm I, I.l-trichloroethane and 200 ppm trichloroethylene together in the atmosphere of a I m3 exposure chamber for 6 hr daily for 4 days. On day 5, two animals were killed immediately and two groups of four each were further exposed to the solvents for 2 hr or 6 hr before they were killed. Brain, liver, lung and perirenal fat samples were taken for estimation of the compounds. After 4 days, marked accumulation of trichloroethane was found in perirenal fat, but no trichloroethylene appeared there until the exposure on day 5. Brain retention of the two compounds was in the ratio 8:1 (l.I,I-trichloroethane:trichloroethylene), and a similar relative distribution occurred in lung tissue. In liver, the trichloroethylene concentration decreased towards the end of the experiment on the fifth day. The brain-protein content was not significantly altered by combined exposure, but in rats re-exposed on day 5 for 6 hr there was a reduction in brain RNA. Acid-proteinase activity was increased in rats after the 2-hr exposure on day 5 but was normal after the 6-hr exposure. Brain glutathione was not affected by the exposure. Microsomal drug-metabolizing activity in