Short-chain, 2- and 3- carbon halogenated hydrocarbons were tested for mutagenicity for Salmonella typhimurium strain TA 100 both with and without the presence of S-9. Without exception, all brominated derivatives were more mutagenic than the chlorinated derivatives, usually by a substantial order of magnitude. 2-Fluoroethanol, the only fluorinated compound tested, showed little or no mutagenic activity up to 100 micromole per plate concentration. Two highly purified propane derivatives containing a halogen atom on each of the three carbons showed little or no direct mutagenic activity. A third trihalogenated compound with a halogen atom on each carbon atom showed some direct mutagenic activity, probably due to impurities. However, all three trihalogenated compounds were highly active mutagens following S-9 activation. The presence of a double bond in the case of 1, 2, 3-trichloropropene resulted in a higher level of direct mutagenic activity than 1, 2, 3-trichloropropane, but activation with S-9 resulted in a further increase in mutagenic activity with the former compound. On the other hand, S-9 caused a substantial decrease in mutagenic activity of most compounds containing a double bond. With the presence of an alcoholic group in a compound, the addition of S-9 caused variable responses, increasing the number of his+ revertant colonies due to 2, 3-dibromopropanol but had little or no effect with five other compounds containing an alcoholic group. Evidence is also presented that the position of a double bond in relation to the halogen atoms may influence mutagenic activity.

Four structurally related three-carbon compounds, known for their antifertility activity in the male, and the brominated derivatives of two of these compounds were tested for mutagenic activity by the Salmonella typhimurium test of Ames et al. In the presence of strain TA-100, a base-pair substituion detector strain, 1,2-dibromo-3-chloropropane (DBCP), was the most active compound tested but required enzymatic conversion by 59 microsomal preparation to an active mutagen. Three of these compounds containing an epoxide group-epichlorohydrin, epibromohydrin, and glycidol-were highly active direct mutagens, not requiring 59 for activation, alpha-Chlorohydrin was the least active compound tested; alpha-bromohydrin was 40 times more active than its chlorinated analog. Epibromohydrin was only slightly more active than epichlorohydrin, but both were highly active. With both of the halogenated epoxides, 59 preparation caused a substantial decrease in mutagenic activity at every concentration tested. All six compounds showed dose-related responsiveness for the base-pair substitution detector strains used. However, they were relatively inactive against the frameshift detector strain of S. typhimurium, TA-98. Glycerol, propylene glycol, and n-propanol, which are also three-carbon compounds containing one or more hydroxy groups, were inactive when trested at high concentrations with strain TA-100.

At five stages of gestation, mice were exposed dorsally to ultrasonic irradiation at 1 W/cm2 (spatial and temporal average), 2 MHz, and 34 and 37 degrees C (temperature at beginning of exposure). The results indicated that ultrasonic exposure up to at least 100 s is not hazardous to a pregnant mouse or its offspring in utero under the conditions of our experiment. Thresholds for both undesirable and lethal effects on the dam and its embryos or fetuses appeared between 100 and 200 s. Temperature rises in the uterus to more than 40 degrees C and similarity of results obtained with continuous-wave and burst modes of irradiation suggest a thermal mechanism as one cause of these effects. Preliminary conclusions are that thresholds for both tissue damage to the dam and deleterious effects on pregnancy were similar; however, they occurred at spatial average intensity and exposure levels far in excess of those used in clinical diagnostic medicine.

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The Nonhuman Primate Pregnancy Test may be useful for diagnosis of pregnancy in squirrel monkeys between 40 and 60 days in pregnancy. However, single determinations have an inherent 10% risk of false negative responses caused by low chorionic gonadotropin levels; thus, initial negative test responses should be followed within one week by an independent confirmatory test. Preliminary results with this hemagglutination inhibition test compare favorably with bioassay and may be useful, in conjunction with conventional uterine palpation, for diagnosis of pregnancy in squirrel monkeys.