Acute Oral and Dermal Toxicity of Quadricyclane

Abstract

Quadricyclane CASR 278-06-8 Compound Tested: Oral -Neat and as 70/30 mixture with kerosene Dermal -Neat Dose Preparation: Test and Results:Oral Lethalitv Protocol: Male Fischer 344 rats were fasted for approximately 16 hours prior t o administration of the oral dose. Each rat was weighed prior to dosing and the test compound was administered on a g/kg basis. Five rats received a dose of 3.5 g quadricyclane/kg; five rats received a dose of 1.7 g/kg of a quadricyclane/kerosene mixture (70% to 30%); five rats received a dose of 4.3 g kerosenelkg; and five rats received 5 g salinefkg to serve as controls. Surviving animals were held 14-days posttreatment. Results: All were prostrate immediately following dosing and remained so until death. 1.1 g/kg mixture resulted in prostration in all rats through 24 hours posttreatment; returned to normal appearance and activity by 4 8 hours and survived the 14-day posttreatment period. Tissues examined from animals following death were equivocal. Tissues from animals that survived the 14-day posttreatment period appeared normal. These data indicate an LD, between 1.2 and 3.5 g/kg.Dermal Lethality Protocol: Five male albino New Zealand White rabbits were used. The saddle area was clipped and the neat compound was applied at the EPA limit level of 2 g/kg body weight. The area was covered with gauze bandage and dental dam. The entire midsection was then wrapped in elastoplast tape. After 24 hours, the covering was removed and excess compound was wiped from the rabbit. The rabbits were observed 14-days posttreatment. Results: One of the five rabbits died of accidental injury during the treatment period. The four remaining rabbits survived the 14-day posttreatment period and appeared normal upon gross examination.3.5 g/kg neat compound resulted in total mortality within 24 hours.

Synthetic Chemistry of Quadricyclane

“…As it was shown latter, the reaction of Q with maleic (3) and monochloromaleic (4) anhydrides, dimethylmaleate (5), dimethylfumarate (6), fumaro-(7) and maleo - (8) nitriles is regio-and stereospecific and leads to exclusive formation of exo-tricyclo [4.2.1.0 2,5 ]non-7-enes 9-14 [27,28].…”

“…The reaction at elevated temperature leads to the mixture of 5 isomeric C 21 trimers [136]. Si(OBu-t) 3 8.7 -- [107] a cycloadduct of p-terafluoroquinone and Q; b cycloadduct of p-tetrachloroquinone and Q; c cycloadduct of p-tetrabromoquinone and Q; * structure confirmed by single crystal X-ray diffraction.…”

“…The geometry of two isomeric cycloadduct of CF 3 C(O)F and Q (ratio isomers 75 : 25) was established in 2D 1 H-19 F HOESY (2D Heteronuclear Proton-Fluorine NOE) experiment. In major isomer syn-orientation of F-4 relative to CH 2 -bridge was established based on observed large NOE between F-4/H-9' and CF 3 -4/H-5 along with a smaller NOE for CF 3 The observed qualitative order of reactivity of fluorinated carbonyl compounds toward quadricyclane indeed increases with the electron deficiency of the carbonyl group [75]:…”

“…Tetrakis(triphenylphosphine)palladium, after being exposed to air for 1-2 h, becomes highly active catalyst for codimerization of Q and endo, exo-h e x a c y c l o [9.2.1.0 2,10 .0 3,8 .0 4.6 .0 5,9 ]tetradec-12-ene. The reaction at elevated temperature leads to the mixture of 5 isomeric C 21 trimers [136].…”

“…It was reported to produce100% mortality in male Fischer 344 rats within 24 h following gavages at 3.5 g/kg [3]. Combined data of oral and dermal toxicity studies indicated an LD 50 for Q being between 1.2 and 3.5 g/kg [3].…”