V. Drugs and chemical substances 1) Thalidomide 2) Actinomycin D 3) Streptonigrin 4) Chlorambucil 5) Dextroamphetamine 6) Urethane and hydroxyurea 7) Aflatoxin B_1 8) Purine analogues 9) Methyl salicylate 10) Beta-amino- 11) Trypan blue 12) Others propionitril (BAPN) VI. Zinc deficiency and cadmium VII. Tissue antiserum VIII. Hormone The problems concerning the abnormal development of the heart were discussed and summarized according to the following items: 1. The role of the genome during cardiogenesis in the embryo 2. The patterns of cardiovascular anomalies produced by different agents 3. The relationship between embryonic stage at which agents are administered and frequency of heart anomalies manifested 4. Morphology of the abnormal cardiogenesis in early stages of embryos 5. The relationship between anomalies and chromosome changes in the embryo treated with various agents 6. The relationship between anomalies and lysosome formation in embryonic cells 7. The relationship between anomalies and LDH-isozyme differentiation in early states of embryos

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Teratogenic effects of excessive vitamin A on the rabbit were examined morphologically. The rabbits used were those of jw/NIBS strain, which have been bred as a closed colony at Nippon Institute for Biological Science, Tokyo for about twenty years. The females were given a single, intraperitoneal injection of water-miscible vitamin A palmitate at a dose of 300,000 IU/kg body weight on day 8, 9, 10, 11, 12, 13, 14 or 15 of pregnancy. The fetuses were removed from the mothers by cesarean section on day 28 of pregnancy, and were examined for gross and skeletal malformations. The skeletal checks were done after clearing the soft tissues with KOH and stainning the bones with alizarin red S. In the group treated on day 8, all embryos died. In the groups treated from day 9 today 15, various gross and skeletal malformations were observed. General retardation of growth was also evident. The gross malformations manifested were cranio-facial malformations, auricular malformations, cleft palate, pseudomacroglossia, open-eyelid, short-tailedness, club foot, micromelia, ectrodactylism, syndactylism and brachydactylism. In the groups treated on day 9, 10 or 11, the malformations were produced with high frequencies. Their incidences reduced as the developmental stage of treatment advanced. The cranial malformations in the groups treated in the early stages of organogenesis showed a hypoplasia of the skull bones ; while those in the groups treated in the later stages revealed fusions or protuberances of the parietal and frontal bones. These findings suggested that the types of cranial malformations would vary according to the developmental stages at which the embryos were being insulted. The facial malformations showed hypoplasias of the nasal bones, maxillas, premaxillas and mandibles. The micromelias showed a shortening and thickening of the long bones. Fusion of the humerus and radius the elbow joint was also found in some cases of micromelia.

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Wister rats were treated with a single intraperitoneal injection of 0.2mg/kg of vincristine of day 8 of pregnancy, and the fatuses were examined externally on day 20. Major malformations were as follows: Anophthalmos and microphthaomos were 44.10%, malformations of the CNS were 45.13%, and those of the face were 48.21%. On malformations of the eye, bilateral cases were 66.28% and unilateral ones were 33. 72%. Malformed eyes on the right side were 47.55%, and those on the left side were 52.45%. Incidence of anophthalmos was 53.85%, that of microphthalmos was 45.45%. Besides, there were open eyelids, 6.29%. When they were examined histologically, almost all cases grossly diagnosed as anophthalmos were proved to be microphthalmos which had some components of the eye cup. Under a microscope, there were found few complete anophthalmos, many microphthalmoses of extreme degree, "some with complicated retinal foldings, few with slight coloboma of the retina, etc. Another series of experiments were dynamic studies of the abnormal morphogenesis of the eye. Embryos were examined on day 10, i. e. , two days after the treatment; thereafter they were taken out every 24 hours until day 19. These were examined histologically. A11 cases examined on day 10 had the eye vesicle. Even those with intense cranioschisis also had the eye vesicle. However, on day 11 when the eye vesicle develops into the eye cup, the process of the development was arrested or involved in an abnormal condition. When embryos were examined on day 12, the eye cup was small in size suggesting sequential microphthalmos. Of those examined of day 13, there were cases suggesting initial involvement which would lead to anophthalmos. In such cases, only rudiments of the eye cup were detected. On the later stages of the development, i. E., after day 13, besides cases of the above mentioned abnormal conditions, absence of the optic nerve and sometimes malformations of the diencephalon were associated. In the above results, a spectrum of malformations of the eye was observed such as from a complete anophthalmos to a slight coloboma of the retina. However, these malformations of the eye induced by vincristine were generally similar to those produced by other extrinsic factors. All cases of anophthalmoses were degenerative anophthalmoses, and no cases of primary anoththalmos were found.

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