[Single and 2-week repeated intravenous dose toxicity studies of disodium mercaptoundecahydro-closo-dodecaborate in rats].
Disodium mercaptoundecahydro-closo-dodecaborate (BSH) is a boron compound used in Boron Neutron Capture Therapy for malignant brain tumors. Intravenous single and 2-week repeated dose toxicity studies of BSH were performed in Sprague-Dawley rats. In the single-dose study, BSH was administered at doses of 100, 300 or 600 mg/kg. Death occurred within 10 min (acute type) or from 5 hr to 2 days (delayed type) after dosing in the 600 mg/kg group. No differences in mortality by sex and dosing speed were observed. Major causes of death were considered to be circulatory disorder in acute death and renal injury in delayed death. The renal injury was observed in the 300 and 600 mg/kg groups. In the 2-week repeated dose study, BSH was administered at doses of 30, 100 or 300 mg/kg/day for 14 days. Body weight gain was suppressed in the 100 and 300 mg/kg groups. One male in the 300 mg/kg group died due to renal and pulmonary lesions at day 8. Slight anemia was observed in the 300 mg/kg group. Pathologically, the kidney showed tubular regeneration with increase of weight in the 300 mg/kg. From these results, the NOAEL of BSH is 30 mg/kg/day.
Itoh
F
F
Developmental Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Yabuuchi
K
K
Ohno
K
K
Ikeuchi
I
I
Muraoka
Y
Y
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001894:Borohydrides / Q000633:toxicity*; D001895:Boron / Q000097:blood; D001896:Boron Compounds / Q000633:toxicity*; D005260:Female; D007275:Injections, Intravenous; D007674:Kidney Diseases / Q000139:chemically induced; D008099:Liver / Q000737:chemistry; D008297:Male; D011041:Poisoning / Q000097:blood / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013438:Sulfhydryl Compounds / Q000633:toxicity*
D001894:Borohydrides; D001896:Boron Compounds; D013438:Sulfhydryl Compounds; C014651:mercaptoundecahydrododecaborate; D001895:Boron