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CF1 female mice were time mated and the embryos at each gestation day from 0.0 to 18.0 were x-rayed to l O O r and the young carried to four months at which time a skeletal study was made. With this exposure the litters were reduced in size, following irradiation at certain gestation ages, and there was neo-natal mor. tality so that this skeletal study is based upon the survivors to four months and represents the maximum development under the conditions of irradiation. The sex ratio was not altered by this irradiation. Male mice of this strain are always heavier than the females of the same age, and this exposure reduced the over-all average of either sex by 2.5 grams. The skeletal measurements were taken from 1,005 radiographs of the living animals, and the averages calculated for each gestation day. There were sex differences in stunting, even when x-irradiation occurred before day 9.0. When the differences were pronounced the female was the more adversely affected. The highest statistical significance in skeletal effects of seven measurements was between 11 and 13 days, when the embryo shows the earliest skeletal differentia. tion. Such mice were topographically well developed.

An exposure of 100 r X-rays to the mouse embryo or fetus at certain stages of develop ment results in a statistically significant increase in the ultimate appearance of cataracts. In fact, 97% of those X-irradiated during the first few hours after conception developed cataracts by 18 months, thus demonstrating that an exposure of this level (100 r) is permanently damaging ( 1 ) .A parallel study was made on the weight changes at various ages and the incidence of palpable tumors in surviving mice, the results of which are reported here. It has already been suggested that weight changes following whole body X-irradiation of adult mice constitute a reliable biological dosimeter equal to the LDJ50/30 data(2-5).Materials and method. The CF1 mice used in this study previously had normal litters, close to the average size of 9.2 per female. They were mated with normal males of the same strain for a 2-hour period in the early morning, and the mated mice (with vaginal plugs) were subsequently X-rayed a t various intervals from immediately after conception to 18 days. The exposures thereafter were at daily intervals to different pregnant females until 18 days gestation, shortly before the time of expected delivery at 19 days. The newborn mice were given in equal numbers of 8 to foster mothers which were substituted for natural mothers to eliminate any indirect influence of X-irradiation ( 6 ) , and were weaned at the proper time, sexed and segregated at 1 month of age. There were then selected at random from among the irradiated survivors 25 males and 25 females from each gestation age and simultaneously 50 control males and 50 control females kept under identical conditions.

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CF1 mice were exposed to x-rays during development at various intervals from 0.5 day after conception to 18 days. The levels of x-irradiation were previously established for each gestation day so that half of the exposed fetuses would survive for at least 30 days after birth. Those that survived to two months were radiographed (1,174 mice including 150 controls of the two sexes) and seven bone measurements were taken from each mouse. From conception through gestation day 10 there appeared to be no significant reduction in bone measurements as a result of embryonic or fetal x-irradiation even though the exposures ranged from 100 R to 400 R. The greatest decrements followed exposure of the fetuses at days 15 and 16, although there was some reduction on days 13 and 14 also. The spine measurements were first reduced when x-irradiation was done on day 11. In both the controls and those x-rayed the average bone measurements were slightly greater for the males than for the females. Embryologically those days most radiosensitive with respect to skeletal growth were those when osteogenesis was the most active. There is no evidence that ionizing radiations prior to chondrogenesis has any effect on later skeletal development.A prior study (Rugh et al., '64) showed that mouse embryos exposed to a uniform dose of 100 R x-rays a t various gestation stages were permanently stunted to various degrees depending specifically upon the gestation age at the time of x-irradiation. It was found that days 11 and 12 were the most radiosensitive as determined by skeletal deficiencies among the seven measurements taken and that whenever there was an effect, it was more pronounced in the female than in the male.A uniform radiation exposure at different gestation ages does reveal the variations in radiosensitivity of skeletal development, probably related to the presence of metamorphosing osteoblasts. It has been established that there are reliable LD/50 (lethal doses to 50% of exposed embryos) data for each gestation day (Rugh and Wohlfromm, '62) and more recently the same investigators ('65) established the LD/50/30 dose of x-rays to the embryo at various gestational ages which will allow 50% to survive for the first 30 days after birth. Curiously, it was found that the exposure level after day 9 which would kill half of those delivered within their first 30 days of life, was even lower than that which killed half in utero. This pointed up the importance of trying to determine how normal were those mice that did survive during their first 30 days of life. Thus, for this study each gestation day had a different x-ray exposure level as shown by these independent LD/50 and LD/50/30 studies so that analysis of the seven selected bone measurements reflects the permanent effect on the skeleton of those that were able to survive a considerable level of exposure to x-rays while in utero. In a prior study (Rugh et al., '64), a uniform exposure of x-rays was used, but here the base line was 50% survival and this, of necessity, required diff...