Acute and neurotoxicity of two structurally related acetylenic compounds: 5,7,11-dodecatriyn-1-ol and 5,7,11,13-octadecatetrayne-1,18-diol.
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 bilateral 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.
Gad
S C
SC
Department of Toxicology, Allied Corporation, Morristown, NJ 07960.
Dunn
B J
BJ
Gavigan
F A
FA
Reilly
C
C
Peckham
J C
JC
D000480:Alkynes / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000473:pathology; D005233:Fatty Alcohols / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000187:drug effects; D006168:Guinea Pigs; D007509:Irritants; D007928:Lethal Dose 50; D008297:Male; D009153:Mutagens; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010787:Photosensitivity Disorders / Q000139:chemically induced; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D012871:Skin Diseases / Q000139:chemically induced
D000480:Alkynes; D005233:Fatty Alcohols; D007509:Irritants; D009153:Mutagens; C055567:5,7,11-dodecatriyn-1-ol; C055568:5,7,11,13-octadecatrayne-1,18-diol