[Study on hepatoxicity and nephrotoxicity of cinnabar in rats].
OBJECTIVE
To investigate hepatoxicity and nephrotoxicity of cinnabar to provide the scientific basis for safe uses in clinic.


METHODS
Maximally tolerated dose of cinnabar (MTD) was tested by single oral administration. Chronic toxicity of cinnabar at different dose level (0.025, 0.05, 0.1, 0.4, 0.8 g x kg(-1) x d(-1)) corresponding to 1/2, 1, 2, 8, 16 times of clinic doses of cinnabar was investigated. The rats were treated with the cinnabar through oral administration once a day for successive 90 days. Urinary qualitative test, blood routine examination, serum chemistry measurement and histomorphologic observation were conducted at day 30, 60 and 90. Toxic changes related to the treatment of cinnabar and no-observed adverse effect level (NOAEL) were evaluated.


RESULTS
For the content of 98.1% total Hg and 21.5 microg x g(-1) absoluble Hg, MTD of cinnabar with oral administration was 24 g x kg(-1) (corresponding to 516 microg x kg(-1) absoluble Hg), equivalent to 3,000 times of clinical daily dose for an adult, and no obvious adverse effect was showed at this dose. Cinnabar can cause kidney and liver pathological changes when it is repeatedly administrated for over 30 days. The kidney was more sensitive to cinnabar than liver. Based on repeated dose toxicity study, NOAELs were 0.1, 0.05 g x kg(-1) x d(-1)) respectively for 30 day and 90 day treatment, and those were approximately accumulative intake of absoluble Hg 64.5 microg x kg(-1) and 96.76 microg x kg(-1). Thus, for safe use of cinnabar, the acceptable daily intake (ADI) of cinnabar was 0.0009-0.0017 g x kg(-1) x d(-1), namely daily dose 0.05-0.1 g for an adult with body weight about 60 kg. Considering the difference of drug sensitivity and lifecircle between human and rats, we suggest that cinnabar which contains absoluble Hg < or = 21 microg x g(-1) should be used for no longer than 2 weeks at daily dose 0.05-0.1 g.


CONCLUSIONS
Long term use of cinnabar can cause kidney and liver pathological change, so the dose and administration duration should be limited. The suggestion is as follows: cinnabar which contains absoluble Hg < or = 21 microg x g(-1) should be used less than 2 weeks at the daily dose below 0.05-0.1 g.
Liang
Aihua
A
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China. liangaihua@sina.com
Wang
Jinhua
J
Xue
Baoyun
B
Li
Chunying
C
Liu
Ting
T
Zhao
Yong
Y
Cao
Chunyu
C
Yi
Yan
Y
D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017669:Mercury Compounds / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D017669:Mercury Compounds; C034211:cinnabar