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Persistence of micronuclei in peripheral blood normochromatic erythrocytes of subchronically benzene-treated male mice.

The kinetics of micronucleus (MN) induction and decline in blood normochromatic erythrocytes (NCE) of mice subchronically exposed to benzene was investigated during and after exposure. Swiss (ICR) male mice (10/group) were given 0.0, 36.6, 73.2, and 146.4 mg/kg body weight benzene by gavage daily for 14 days, except for days 5 and 10. The frequency of MN increased significantly (P less than .001) during benzene treatment as a function of both concentration and time. Eleven days after exposure the levels of MN were higher than those observed at the end of exposure. After an initial rapid decline in the frequency of MN from 11 to 18 days postexposure, the decline became linear with time through 60 days postexposure. Using linear regression analysis, the MN level in each treatment group was predicted to reach control levels by approximately 85 days post-treatment. Dose-dependent suppression and recovery of erythropoiesis, estimated by polychromatic erythrocyte frequency, were observed in the 1st and 2nd weeks of exposure, respectively. Red blood cell (RBC) production was markedly increased in the first 3 weeks after benzene treatment. At later times the rate of production of the RBC returned to normal and may account for the linear decline observed in MN frequency. This research indicates that the frequency of MN is dose and duration dependent, while the decline in MN frequency after the end of benzene exposure can be related to changes in the kinetics of erythropoiesis.

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Responses of the l5178y tk<sup>+</sup>/tk<sup>−</sup> mouse lymphoma cell forward mutation assay: III. 72 Coded chemicals

Seventy-two chemicals were tested for their mutagenic potential in the L5178Y tk+/- mouse lymphoma cell forward mutation assay, using procedures based upon those described by Clive and Spector (Mutat Res 44:269-278, 1975) and Clive et al. (Mutat Res 59:61-108, 1979). Cultures were exposed to the chemicals for 4 hr, then cultured for 2 days before plating in soft agar with or without trifluorothymidine (TFT), 3 micrograms/ml. The chemicals were tested at least twice. Significant responses were obtained with allyl isothiocyanate, p-benzoquinone dioxime, benzyl acetate, 2-biphenylamine HCl, bis(2-chloro-1-methylethyl)ether, cadmium chloride, chlordane, chlorobenzene, chlorobenzilate, 2-chloroethanol, chlorothalonil, cytarabine.HCl, p,p'-DDE, diazinon, 2,6-dichloro-p-phenylenediamine, N,N-diethylthiourea, diglycidylresorcinol ether, 2,4-dimethoxy aniline.HCl, disperse yellow 3, endosulfan, 1,2-epoxyhexadecane, ethyl acrylate, ethyl benzene, ethylene thiourea, F D and C yellow Number 6, furan, heptachlor, isophorone, mercuric chloride, 4,4'-methylenedianiline.2 HCl, methyl viologen, nickel sulfate.6H2O, 4,4'-oxydianiline, pentachloroethane, piperonyl butoxide, propyl gallate, quinoline, rotenone, 2,4,5,6-tetrachloro-4-nitro-anisole, 1,1,1,2-tetrachloroethane, trichlorfon, 2,4,6-trichlorophenol, 2,4,5-trimethoxybenzaldehyde, 1,1,3-trimethyl-2-thiourea, 1-vinyl-3-cyclopetene dioxide, vinyl toluene, and ziram. Apart from 2-biphenylamine.HCl, 2-chloroethanol, disperse yellow 3, ethylene thiourea, FD and C yellow number 6, phenol, and 1,1,2-tetrachloroethane, rat liver S9 mix was not a requirement for these compounds. Chemicals not identified as mutagens were acid red, 11-aminoudecanoic acid, boric acid, 5-chloro-o-toluidine, coumaphos, cyclohexanone, decabromodiphenyl oxide, di(2-ethylhexyl)adipate, ferric chloride, fluometuron, melamine, monuron, phenesterin, phthalimide, reserpine, sodium dodecyl sulfate, 4,4-sulfonyldianiline, tetrachloroethylene, and zearalenone. The assay was incapable of providing a clear indication of whether some chemicals were mutagens; these were benzyl alcohol, 1,4-dichlorobenzene, phenol, succinic acid-2,2-dimethyl hydrazide, and toluene.

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