Cashman J R, Traiger G J, Hanzlik R P
Toxicology. 1982;23(1):85-93. doi: 10.1016/0300-483x(82)90044-0.
Primary thiomides such as thiobenzamide (TB) are well known hepatotoxins in the rat. Among para-substituted TB derivatives relative hepatotoxicity varies in accordance with the electronic properties of the parasubstituent. In contrast, several N-substituted TBs have been found to be potent lung toxins in rats and mice. For N-methylthiobenzamide (NMTB) the LD50 was found to be 0.315 (95% confidence interval (CI) 0.228-0.436) mmol/kg in the rat and 0.224 (95% CI 0.191--0.264) mmol/kg in the mouse. The N-mono-substituted TBs produce alveolar and perivascular pulmonary edema, together with massive pleural effusions (hydrothorax). In this regard their toxicity resembles qualitatively that of the arylthioureas. Furthermore, pretreatment of rats with sub-lethal doses of NMTB was found to protect them against subsequent challenge with supra-lethal doses. N,N-Dimethylthiobenzamide (DMTB) also causes lung injury in the rat, but only at much higher doses than with the N-mono-substituted TBs. The similarity in toxic responses elicited by the N-mono-substituted TBs and the arylthioureas is paralleled by similarities in their chemical structures and their metabolic disposition which involves (among other things) S-oxygenation by the microsomal flavin-containing monooxygenase (EC 1.14.13.8). Thus, a possible role for S-oxidized metabolites in the lung toxicity of these compounds must be considered.
诸如硫代苯甲酰胺（TB）之类的一级硫代酰胺是大鼠中广为人知的肝毒素。在对位取代的TB衍生物中，相对肝毒性根据对位取代基的电子性质而变化。相比之下，已发现几种N-取代的TB在大鼠和小鼠中是强效的肺毒素。对于N-甲基硫代苯甲酰胺（NMTB），在大鼠中的半数致死剂量（LD50）为0.315（95％置信区间（CI）0.228 - 0.436）mmol/kg，在小鼠中为0.224（95％CI 0.191 - 0.264）mmol/kg。N-单取代的TB会导致肺泡和血管周围肺水肿，以及大量胸腔积液（胸腔积水）。在这方面，它们的毒性在性质上类似于芳基硫脲。此外，发现用亚致死剂量的NMTB预处理大鼠可保护它们免受随后超致死剂量的攻击。N，N-二甲基硫代苯甲酰胺（DMTB）也会在大鼠中引起肺损伤，但所需剂量比N-单取代的TB高得多。N-单取代的TB和芳基硫脲引发的毒性反应相似，这与它们的化学结构和代谢处置相似，其中包括（除其他外）通过微粒体含黄素单加氧酶（EC 1.14.13.8）进行S-氧化。因此，必须考虑S-氧化代谢物在这些化合物肺毒性中的可能作用。
