Acute and neurotoxicity of two structurally related acetylenic compounds: 5,7,11‐dodecatriyn‐1‐ol and 5,7,11,13‐octadecatetrayne‐1,18‐diol

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Abstract
Two structurally related acetylenic compounds, 5,7,11‐Dodecatriyn‐1‐ol, (Compound A), and 5,7,11,13‐Octadecatetrayne‐1,18‐Diol (Compound B), were evaluated in a tier I toxicology testing program as part of an ongoing research and development program. This battery of acute tests included acute oral, guinea pig maximization, photosensitization, dermal irritation, Ames and multiple genetic endpoint and a 2 week oral fetotoxicity study. Compound A was found to have an oral LD50 of 0.25 ml/kg, be an extreme dermal sensitizer, a mild dermal irritant (PDII of 1.7), and not mutagenic or fetotoxic in the tests employed. Compound B had an oral LD50 greater than 4 g/kg, was a moderate dermal sensitizer and mild dermal irritant (PDII of 1.4), was not mutagenic in the Ames test but weakly increased the incidence of SCEs and gene mutations in Chinese Hamster Ovary cells, and was not fetotoxic. Neither compound was found to be a photosensitizer, but during the course of the photosensitization study Compound A was found to cause neuromuscular signs (including hind limb paralysis) and a bilaterial necrosis of the medulla oblongata in female guinea pigs. A similar lesion was found in female rats receiving a single oral dose of 0.25 ml/kg and in nonpregnant females dosed daily for two weeks at 0.03 ml/kg. Compound B was not found to produce any of these neurologic effects.