The alkylating agent busulfan (1,4‐butanediol dimethanesulfonate) was given to mice on day 1 to 18 of pregnancy, each animal receiving a single 30 mg/kg ip dose. Growth and mortality rates from birth to the end of the 8th week were observed in 510 young. Starting from the gestation day 9 treatment caused significant growth retardation in 51.2% of offspring. The frequency was highest when injections were given on day 10, 15, or 16. Treatment on day 9, 10, 15, 16, or 17 was associated with an overall death rate of 37.6%. There was a direct relation between retarded growth and premature death, and both occurred chiefly in animals treated during fetogenesis. In 23.8% of the young from females treated on day 10, 11, or 12 extreme stunting, wasting, abnormal hair, skeletal muscle weakness, and, in two cases, necrotic foci in the liver were associated with hypoplasia of the thymus; 30% of the animals died before the end of the 1st month. Damage of some or all the thymus cell precursor lines was probably the origin of the hypoplasia of this organ, which, in turn, was the likely cause of the other features of the syndrome. These results emphasize the need for studying postnatal development when testing embryopathic effects of drugs, and point to the possibility of using busulfan as an experimental model in the study of the thymus ontogenesis and development of immune responsiveness.

The accidental finding of near-term mouse fetuses exhibiting limb positions that could have been interpreted as malformations but that were, in fact, spurious, led us to study the posture of the limbs in the offspring of 100 CD-1 mouse dams. A total of 1,015 fetuses (18 days-old, vaginal plug: day 0), was examined. Fifteen of these fetuses presented positions that deviated markedly from the norm and were therefore considered to be "unusual," although the usual position was recovered in 6 of the 15 by placing the affected limb in a standard position and eventually eliciting locomotion. A broad review of the literature was made in order to evaluate our results fully. This review included 43 reports published in Teratology that recorded abnormal limb positions in near-term mouse and rat fetuses, and another 9 reports where these were not referred to but that included photographs showing such abnormalities. The data obtained from our experimental study and review led us to conclude that for a correct record of abnormal positions in near-term mouse and rat fetuses, authors must follow appropriate, clearly described technical procedures, including maneuvers to rule out spurious displacements; give adequate information in the legends of the photographs; use unequivocal terminology; and carry out further research to determine accurately the range in variation of normal limb positions.

Due to the translucency of the skin and underlying soft tissues, the external examination of near-term mouse fetuses can be extended to parts of the skeletal, visceral and vascular systems which are not taken into account in the protocols of teratogenicity tests. The importance of such visualization for improving the accuracy of such tests is discussed.

In 1,015 CD-1 near-term mouse fetuses, removed by cesarean section after cervical dislocation of dams, skin color, motility, crying, and breathing were studied. Three categories of fetuses were considered: living and surviving (92.5%); living but non-surviving (6.9%), and stillborn (0.6%). Particular attention was paid to the following: 24 fetuses, still apneic after routine manipulation, started breathing by specific maneuvers; 5 of these 24 fetuses were apparently dead when apnea recovery was successfully tried, and the living but non-surviving category must be considered in developmental toxicity screening as prenatal injuries may be manifested by an increase in the incidence of the fetuses belonging to this category.

No abstract