Liang Aihua, Li Chunying, Wang Jinhua, Xue Baoyun, Li Hua, Yang Bing, Wang Jingyu, Xie Qing, Nilsen Odd Georg
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Zhongguo Zhong Yao Za Zhi. 2011 Jul;36(14):1889-94.
To investigate the toxicity of realgar and provide the scientific basis for safety use of realgar in clinic.
Acute toxicity was tested by single oral administration. Chronic toxicity of realgar was tested at different dose levels (5, 10, 20, 80, 160 mg x kg(-1) x d(-1)) which correspond to 1/2, 1, 2, 8, 16 times of human dose levels. The rats were treated with the test substances through oral administration once daily for successively 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 realgar and no-observed adverse effect level (NOAEL) was evaluated.
With the content of 90% total arsenic and 1.696 mg x g(-1) soluble asenic, LD50 of Realgar with oral administration was 20.5 g x kg(-1) (corresponding to 34.8 mg x kg(-1) soluble arsenic), equivalent to 12 812 times of clinical daily dose for an adult. Realgar can cause kidney toxicity or/and liver toxicity after administration for over 30, 60 or 90 days respectively. The kidney was more sensitive to realgar than liver. Based on repeated dose toxicity study, NOAELs were 160 mg x kg(-1) x d(-1) for 30 day's administration, 20 mg x kg(-1) x d(-1) for 60 day's administration, 10 mg x kg(-1) x d(-1) mg x kg(-1) x d(-1) for 90 day's administration respectively. Thus, for safety use of realgar, it is recommended that the daily doses of realgar (with soluble arsenic < or = 1.7 mg x g(-1)) for an adult of the body weight about 60 kg could be 10-160 mg depending on the variation of the treatment duration.
Long term use of realgar can cause kidney and liver pathological change, so the doses and administration duration should be limited. The suggestion is as follows: realgar which contains soluble arsenic < or = 1.7 mg x g(-1) should be used less than 2 weeks at daily dose 160 mg, less than 4 weeks at the dose of 20 mg and less than 6 weeks at the dose of 10 mg.
研究雄黄的毒性，为其临床安全应用提供科学依据。
采用单次灌胃给药法测定急性毒性。以相当于人体剂量水平的1/2、1、2、8、16倍（5、10、20、80、160mg·kg⁻¹·d⁻¹）的不同剂量水平对雄黄进行慢性毒性试验。大鼠连续90天每天经口给予受试物。在第30、60和90天进行尿液定性试验、血常规检查、血清生化测定及组织形态学观察。评估与雄黄治疗相关的毒性变化及未观察到不良反应水平（NOAEL）。
含总砷量90%、可溶性砷1.696mg·g⁻¹的雄黄，灌胃给药的LD50为20.5g·kg⁻¹（相当于可溶性砷34.8mg·kg⁻¹），相当于成人临床日剂量的12812倍。雄黄分别给药超过30、60或90天后可导致肾脏毒性或/和肝脏毒性。肾脏对雄黄比肝脏更敏感。基于重复给药毒性研究，30天给药的NOAEL为160mg·kg⁻¹·d⁻¹，60天给药的为20mg·kg⁻¹·d⁻¹，90天给药的为10mg·kg⁻¹·d⁻¹。因此，为安全使用雄黄，建议体重约60kg的成年人，根据治疗持续时间的不同，雄黄（可溶性砷≤1.7mg·g⁻¹）的日剂量可为10 - 160mg。
长期使用雄黄可引起肾脏和肝脏病理改变，故应限制剂量和用药时间。建议如下：可溶性砷≤1.7mg·g⁻¹的雄黄，日剂量160mg时使用时间应少于2周，20mg时应少于4周，10mg时应少于6周。
