Khera K S
Teratology. 1984 Jun;29(3):411-6. doi: 10.1002/tera.1420290312.
The assumption that major fetal malformations are indicative of a chemical's teratogenic potential was not supported by a literature review of teratology studies conducted in mice. In these studies, dose levels of test agents that manifested maternal toxicity as suggested by reduction in dam's body weight, clinical signs of toxicity, or deaths, also invariably caused reduction in fetal body weight, increased resorptions, and rarely fetal deaths. In several such studies, conducted with maternotoxic doses of structurally unrelated test agents, a consistent pattern of fetal defects was discovered. These defects included exencephaly, open eyes, hemivertebrae, fused arches or centra of lumbar or thoracic vertebrae, fused, missing or supernumerary ribs, and fused or scrambled sternebrae. These defects were absent at drug dosages that were distinctly nontoxic for the mother. In a few studies conducted at two or more maternally toxic doses, the degree and severity of maternal toxicity showed a positive correlation with the incidence and severity of above fetal defects. It is hypothesized that maternal toxicity, on its own, may have an etiologic role in these fetal defects.
主要胎儿畸形表明一种化学物质具有致畸潜力。在这些研究中，受试物的剂量水平若表现出母体毒性，如母鼠体重减轻、毒性临床体征或死亡，也总会导致胎儿体重减轻、吸收增加，且很少导致胎儿死亡。在几项使用对母体有毒剂量的结构不相关受试物进行的此类研究中，发现了一致的胎儿缺陷模式。这些缺陷包括无脑儿、睁眼、半椎体、腰椎或胸椎弓或椎体融合、肋骨融合、缺失或多余、胸骨融合或紊乱。在对母亲明显无毒的药物剂量下不存在这些缺陷。在少数以两种或更多对母体有毒剂量进行的研究中，母体毒性的程度和严重性与上述胎儿缺陷的发生率和严重性呈正相关。据推测，母体毒性本身可能在这些胎儿缺陷中起病因作用。
