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Objective: To explore the correlation between urinary arsenic and health effects through the determination and analysis of urinary arsenic levels in occupational arsenic exposed workers. Methods: In November 2021, 95 workers exposed to arsenic and its inorganic compounds and 31 administrative personnel from a non-ferrous metal smelter in Yunnan Province were selected as the contact group and control group, respectively. Urine forms of arsenic, blood tumor markers, liver function were detected, and micronucleus test was used to analyze the chromosome damage. The correlation between urine forms of arsenic and health effects were analyzed. Results: Compared with the control group, the concentrations of urinary trivalent inorganic arsenic (iAs(3+)) , pentavalent inorganic arsenic (iAs(5+)) , inorganic arsenic (iAs=ΣiAs(3+)+iAs(5+)) , monomethyl arsenic (MMA) , dimethyl arsenic (DMA) and urinary arsenic (ΣiAs+MMA+DMA) at the end of class in contact group were higher ( P <0.05) . There was no statistically significant difference in blood tumor markers and liver function indicators between the two groups ( P >0.05) . Compared with the control group, the peripheral blood micronucleus rate and cell micronucleus rate in the contact group were significantly increased ( P <0.05) . The urinary arsenic, iAs(5+), inorganic arsenic and DMA were positively correlated with peripheral blood micronucleus rate in contact group ( r (s)=0.48, 0.34, 0.37, 0.23, P <0.05) , and the urinary arsenic, iAs(5+), DMA were positively correlated with peripheral blood micronucleus rate ( r (s)=0.48, 0.34, 0.26, P <0.05) . Conclusion: There is a significant correlation between different valence states of arsenic in the urine and abnormal health effects of occupational arsenic exposed workers. It is necessary to strengthen the detection of arsenic species in the urine of occupational arsenic exposed workers to better protect their health.

A pregnant female taken realgar because of superstition, which caused the baby congenital deafness. Auditory test indicated that bilateral auditory brainstem response (ABR) hearing threshold level was greater than 90 dB nHL and auditory steady state response (ASSR) hearing level ranging from 0.5 kHz to 4 kHz was beyond 110 dB HL. Temporal bone CT showed that bilateral cochlear and semicircular canal malformations, with internal auditory canal broadened.

Realgar-containing Niuhuang Jiedu tablet (NHJD) has been applied in clinic for more than 800 years. However, because realgar contains arsenic (As), it has aroused wide concerns and controversies both at home and abroad. Currently, there are two misunderstandings about realgar-containing Chinese patent medicines. First, some people exaggerated realgar's toxicity as that of arsenic. Second, they recommended to remove realgar from traditional Chinese medicine compounds. In this paper, the authors summarized the advance in studies on NHJD, and proposed different opinions: (1) It is inappropriate to take total As as the index in safety evaluation of NHJD. (2) The toxicity of NHJD is dependent on the dose and duration of administration. (3) Realgar is an active ingredient of NHJD, and shall be deeply studied. Classic realgar-containing traditional Chinese medicine prescriptions, such as Niuhuang Jiedu tablet, shall be evaluated with rigorous modern scientific basis, with the aim to guide rational and safe application.

Realgar (90% of AS4S4) and cinnabar (96% of HgS) have been used in traditional Chinese medicines for thousands of years. Both arsenic and mercury are well-known for toxic effects and the safety of realgar-and cinnabar-containing traditional Chinese medicines is of concern. It is considered that any intentional use of known toxic metals in medicine is an unacceptable risk, while an opposing opinion presumes that realgar and cinnabar have clear pharmacological action with tolerable side effects. This review summarized the progress of toxicological study on realgar-and cinnbar-containing traditional Chinese medicines.

Objective: To evaluate the effect and adverse effects of arsenic trioxide (As2O3) in the treatment of primary hepatocarcinoma patients, and conduct the pharmacokinetics study., Methods: A total of one hundred and eleven advanced primary hepatocarcinoma patients in five centers were treated with As2O3 injection 7 - 8 mg/m(2) i.v. qd for 14 days and was repeated after 7 - 14 days. Evaluation of the clinical response and adverse effects was conducted after two cycles of treatment. The patient who had reached partial PR and SD was treated continuously until disease progression or intolerance., Results: Among the 102 patients evaluable for clinical efficacy analysis, there were 7 PR, 71 SD and 24 PD, the response rate was 6.9% and the clinical benefit rate was 76.5%. The quality of life was improved in 22.5% of patients. The pain relief rate was 71.7%, time to progress (TTP) was 97 days, and the median survival time (MST) was 195 days. The major adverse effects were reversible WHO I-II grade gastrointestinal reactions and bone marrow suppression. The results of pharmacokinetic study showed that the distribution and elimination characteristics in vivo was found to be a two-compartment model. The plasma elimination half-life was (23.94 ± 18.39) h., Conclusions: As2O3 is effective in the management of primary hepatocarcinoma, with a significant analgesic effect. To some extent, it can extend TTP and MST in advanced liver cancer patients, while the treatment is well tolerated in the majority of patients.

Objective: To explore arsenic accumulation and toxicity mechanism following long-term use of realgar and provide scientific basis for safety use of realgar in clinic., Method: The realgar which was used in the study contains 90% insoluble asenic sulfide (As2S2) and 1.696 mg x kg(-1) soluble arsenic. Two separate experiments were performed: 1) Twenty-eight fasting SD rats were orally given a single dose of realgar at the dose of 0.8 g x kg(-1) and the other four rats were given ultra-filtrated water served as control group. Blood, hearts, livers, kidneys, lungs and brains of four rats were taken out at 0.5, 1, 2, 4, 8, 16, 36 h respectively after treatment. Asenic quantity of each organ or blood sample was measured. 2) Forty SD rats were randomly divided into four groups: control group and realgar 0.02, 0.08, 0.16 g x kg(-1) groups, each group containing 5 females and 5 males. The rats were intra-gastrically treated with realgar once a day for successively 90 days, while the control group was given ultra-filtrated water. Asenic amount in blood, liver, kidney and brain of each rat was measured in fasting rats at 16 h after last dosing., Result: Asenic amount of blood, liver, kidney, heart, lung and brain increased after single dosing of realgar at dose of 0.16 g x kg(-1), with the order from high to low blood > kidney > lung > liver > heart > brain. Asenic amount was much higher in blood than that in other organs. The feature of asenic distribution in blood following realgar administration may be the basis for its use for leukemia Ninety-day oral treatment of realgar led to significant accumulation of asenic in blood, kidney, liver and brain. The highest asenic accumulation times was found in kidney followed by liver, which was assumed to be associated with nephrotoxicity and hepatotoxicity of realgar. The highest amount of asenic was observed in blood after 90 day's administration of realgar, and the amount of asenic in organs was in the order of blood > kidney > liver > brain., Conclusion: Asenic can be absorbed and extensively distributed in various organs or tissesses after realgar administration in rats. Long-term use of realgar caused high asenic accumulation in various tissueses, including blood, kidney, liver, and brain. The nephrotoxicity and hepatotoxicity of realgar could be associated with the asenic accumulation in relative organs. Blood is the target of the most highest distribution and accamulation of asenic after realgar treatment, that could be associated with the efficacy of realgar on the treatment of leakemia.

Objective: To compare the efficacy and adverse effects between arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) in patients with acute promyelocytic leukemia (APL)., Methods: The clinical data of 71 patients with newly diagnosed APL were retrospectively analyzed. Two groups were classified according to the induction regimens, namely ATO group (n = 41) and ATRA group (n = 30). The complete remission (CR) rate and the time to CR were compared between these two groups., Results: The CR rate was 97.5% in ATO group and 93.3% in ATRA group (P > 0.05). The median time to CR was 29 days (21-45 days) in ATO group, which was significantly shorter than 38.5 days (24-63 days) in ATRA group (P < 0.001). Retinoic acid syndrome occurred in 52.9% of patients treated with ATRA, which affected the further use of ATRA., Conclusions: Both ATO and ATRA have high response rates for newly diagnosed patients with APL. Compared with ATRA, ATO induction therapy has shorter time to achieve CR and less adverse effects, and therefore may be the first-line therapy for APL.

The most serious complication of arsenic trioxide devitalization of dental pulp is alveolar bone chemical necrosis because of iatrogenic perforation of pulp chamber and arsenic trioxide leakage. Arsenic trioxide is protoplasmic poison.When it contacts periodontal tissues, alveolar bone degeneration, necrosis and loss of bone will occur. When the dental of pulp chamber is open, the operator must pay attention to the length and orientation of the bur, with guidance of the dental X-ray film to avoid pulp chamber perforation.

By comprehensively reviewing the origin and history of Niuhuang Jiedu Wan and its "derivatives", we studied the clinical records of realgar, investigated its clinical usage, dosage, efficacy, and toxicity in the literatures. We pinpointed the factors that might be associated with safety problems of Niuhuang Jiedu Pian (Wan) and other traditional Chinese medicine (TCM) preparations containing arsenic substances. In this article we also put forward suggestions for strengthening the surveillance and administration of similar TCM preparations.

Objective: To investigate the chronic hepatic damage in acute promyelocytic leukemia (APL) patients long-term treated with tetra-arsonic tetra-sulfide (As(4)S(4))., Methods: The periodical liver biochemical examinations and ultrasonography results and hepatic fibrosis indicators (P III NP and type IV collagen) of patients were analysed., Results: 106 APL patients treated with As(4)S(4), the median follow-up time was 36 months (6 - 72). The HCV(-) group includes 84 APL patients. During the first course the abnormal rate of the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was 16.7% and 14.5% (higher than the two times of the normal value), the ALT, AST, gamma-glyoxylate aminotransferase (GGT) levels during the first course were statistically higher than As4S4 treatment before (P < 0.05). There were no statistically differences between the ALT, AST, GGT levels after and before treating with As(4)S(4) in half a year, one year, two year, more than three years (P > 0.05). Other biochemical indicators such as ALP, LDH, TBIL, DBIL, TP, ALB, A/G, BUN, CRE, there were no significantly differences before and after As(4)S(4) treatment (P > 0.05). The HCV(+) group includes 22 APL patients, during the first course, the abnormal rate of the ALT, AST were 63.6% and 59.1%, but at the 2 year, more than 3 years there were no significantly differences compared with As(4)S(4) treatment before (P > 0.05). 42 APL patients were treated with As(4)S(4) more than 3 years, in 33 HCV(-) APL patients, two APL patients had splenomegaly, one APL patient's breadth of the portal vein was wider than 1.4 cm, 21 APL patients had fatty liver (63.6%). The hepatic fibrosis indicators of the 16 APL patients were all normal. In 9 HCV(+) APL patients, 4 APL patients had splenomegaly, 2 APL patients, breadth of portal vein were wider than 1.4 cm, 6 APL patients had fatty liver (66.7%). 6 patients were examined with the hepatic fibrosis indicators, 2 patients, were higher than the normal value., Conclusion: Long term As(4)S(4) treatment for APL patients had no obvious effects on hepatic function, no obvious hepatic fibrosis and portal hypertension signs at more than 3 years, excepting for the rate of fatty liver was high.

Objective: To study the main side effects of As(2)O(3) and the way of prevention., Methods: The changes of body weight and various systems of body were observed after treatment with As(2)O(3) injection. The arsenic content in blood, urine and hair was detected with atom absorbed-spectrum analysis., Results: Mild reactions were observed in 57.43% (147/256) of the patients and they could subside after cessation of arsenic treatment or allotherapy. Chronic mild poisoning manifestations including arsenic furuncle, liver dysfunction and peripheral nerve injury were found in 2.73% (7/256) of the patients and they subsided gradually after treatment. Chronic severe poisoning was found in 1.17% of the patients and all of them died of liver failure. As(2)O(3) might cause decrease of peripheral blood WBC in catabatic patients. There was no infection after allopathy without ceasing arsenic medication. The results showed that As(2)O(3) could distribute over and discharge from the plasma without accumulation in blood. The results also demonstrated the main route of excretion for As(2)O(3) is through urine and there is definite accumulation in the hair 50 days after treatment., Conclusion: Most of the side effects of As(2)O(3) are mild and recoverable. Allotherapy could be effective to relieve the complications without stopping arsenic medication. A few patients with complicating hepatitis may suffer from chronic poisoning. As(2)O(3) may cause increase of peripheral blood WBC in induced catabatic APL patients. The side effects must be prevented early.

Objective: To study the pharmacokinetics of multi-dose oral tetra-arsenic tetra-sulfide (As(4)S(4)) in acute promyelocytic leukemia (APL) patients and its major side effects., Methods: Clinical pharmacokinetic study of As(4)S(4) was carried out in 7 patients who had never used arsenic before. The total concentration of arsenic in blood, urine and hair was determined with hydride generation-atomic absorption spectrometry., Results: These patients were administrated oral As(4)S(4) complex capsule 20 mg/kg three times a day for 14 days. From day 10 and to day 14, the blood arsenic concentration and urinary arsenic excretion reached a steady state. The average minimal concentration (Cmin) and maximal concentration (Cmax) of blood arsenic was (53.3 +/- 9.0) microg/L and (70.7 +/- 10.8) microg/L. t 1/2 was prolonged to (70.7 +/- 31.7) hour, and area under curve (AUC) was (448.9 +/- 71.8) microg. h(-1).L(-1). Median time to peak concentration (Tmax) was 1 (range 0.5 - 8) hour. During As(4)S(4) therapy, 24-hour arsenic content in urine was (6170.8 +/- 3141.8) microg/L and it accounted for about (0.152 +/- 0.082)% of the total daily dosage. It decreased steadily over time after drug withdrawal, arsenic accumulated in hair and the concentration could be ten-fold higher than that before treatment., Conclusion: Multi-dose oral As(4)S(4) is safe and has been relatively well tolerated in APL patients in spite of the tendency of its retention in some tissues after long time administration.

Objective: To investigate cardiac effects of arsenic trioxide (As(2)O(3)) at conventional dosage in acute promyelocytic leukemia (APL) patients., Methods: The basical heart rate, electrocardiograph, plasma As(2)O(3) concentration of APL patients were dynamically monitored. The action potential duration and current of I(Ca-L) in guinea pig cardiac ventricular myocytes were assayed by patch clamp technique, and the elevated cytosolic [Ca(2+)]i of guinea pig ventricular myocytes induced by As(2)O(3) by laser confocal microscopy., Results: Approximately 52.5% - 35% of 40 APL patients manifested poor cardiac effects of different degree when As(2)O(3) intravenous infused at conventional doses in the initial 1 or 2 weeks with fast heart rate or prolonged QT interval. As(2)O(3) at concentration of 1, 2, 5 micro mol/L prolonged action potential duration from (563.0 +/- 55.8) ms to (737.7 +/- 131.7), (842.4 +/- 115.6) and (1103.2 +/- 96.3) ms respectively (P < 0.05, P < 0.01, P < 0.01), and increased I(Ca-L) of guinea pig cardiac ventricular myocytes as well as the respectively cytosolic [Ca(2+)]i. Calcium channel blocking agent can cut-out the effect., Conclusion: As(2)O(3) intravenous infusion at conventional doses can cause tachycardia and prolong QT interval. The probable mechanism might be that As(2)O(3) affects the ion channels and cytosolic calcium.

Objective: To study the cardiac toxicity of arsenic trioxide (As(2)O(3))., Methods: To investigate and analyze the probable mechanisms of cardiac toxicity of As(2)O(3) by dynamic monitoring of clinical manifestations, basal cardiac rate and electrocardiographic data of acute promyelocyte leukemia (APL) patients during As(2)O(3) therapy. The instant change of the action potential, the I(Ca-L) and I(k) of single cardiac myocyte of guinea pig was also observed with patch clamp dynamically., Results: Approximately 71.4% of the 28 cases of APL showed cardiac toxic reaction in different degree in the first week after As(2)O(3) intravenous infusion in general dose, mainly expressing rapid heart rate or prolonged QT interval. As(2)O(3) could prolong the action potential duration from (563.0 +/- 55.8) ms to (737.7 +/- 131.7) ms (P < 0.05) and increased the I(Ca-L) and I(k) of single cardiac myocyte of guinea pig in vitro., Conclusion: As(2)O(3) intravenous infusion in general therapeutic dose can cause tachycardia and prolong QT interval in some of the APL patients. The probable mechanism of these side-effects may be due to instant involvement of ionic channel of cardiac myocyte.

Objective: To study whether all-trans retinoic acid (ATRA) combined with arsenic trioxide (As(2)O(3)) in acute promyelocytic leukemia (APL) treatment could further improve the clinical and molecular remission rate., Method: Thirty one newly-diagnosed APL patients of whom 15 were males, 16 females and median age 35.4 years entered into the study. They were treated with ATRA 25 mg x m(-2) x d(-1) combined with As(2)O(3) 0.16 mg x kg(-1) x d(-1) until complete remission (CR). The doses were adjusted according to white blood cell (WBC) counts, occurrence of RA syndrome and the status of liver function. CR rate, time of reaching clinical and molecular remission and side effects were observed., Result: Two patients died 2 approximately 3 days after the treatment due to intracranial hemorrhage, and 29 (93.5%) achieved CR. The average time for achieving CR was 25.1 +/- 3.9 days. Hyperleukocytosis emerged in 66.5% and hepatic damages in 65.5% of the patients, they were ameliorated within one week after reduction of the As(2)O(3) dose or its suspension. The PML/RAR alpha fusion gene that was positive in all 29 patients before treatment turned negative only in 3 cases (10.3%) after obtaining CR (CR1) and in 10/13 cases (77%) after consolidation treatment. Up to now (1-8 months follow-up), all 29 patients remain in CR1., Conclusion: ATRA combined with As(2)O(3) in de novo APL treatment can yield a high CR rate without intolerable side effects. Long term effect needs further observation.

Objective: To observe the efficacy and side effect of the all-trans retinoic acid (ATRA) and arsenic trioxide (As(2)O(3)) combination in acute promyelocytic leukemia (APL)., Methods: Twenty APL patients were treated with the ATRA and As(2)O(3) combination, and 18 of them could be evaluated. The treatment protocol was as following: 10 mg As(2)O(3) (0.1% solution) in 500 ml 50 g/L glucose solution for intravenous drip over 4 to 6 hours once a day, ATRA was given 25 mg/m(2) every day., Results: Seventeen of the 18 patients achieved complete remission (CR), the CR rate was 94.4%. All 14 newly diagnosed patients and 3 of 4 relapsed patients achieved CR. No significant side effect was observed., Conclusion: The As(2)O(3) and ATRA in the treatment of APL can obtain a higher CR rate and a shorter duration for achieving CR.

In order to investigate the toxicity of organic arsenic as well as the mechanism of arsenic carcinogenesis, the GJIC between human skin fibroblast cells is detected by the scrape loading/dye transfer assay and single-cell gel electrophoresis(SCGE) assay is used to detect the DNA strand breaks in human skin fibroblast cells exposed to PhAsO. The results show that gap junctional intercellular communication between human skin fibroblast cells is inhibited by PhAsO significantly with a obvious dose-dependent relationship(P < 0.01), suggesting that PhAsO may act as a tumour promoter. PhAsO could induce DNA strand breaks, but the dose-dependent relationship is not observed. The authors suggest that PhAsO may have tumor promoting activity, and further studies are needed.

Objective: To evaluate the effect and toxicity of arsenic trioxide (As2O3) in treating primary liver and gallbladder cancer., Methods: Twenty-nine advanced primary liver cancer and 4 gallbladder cancer patients were treated with As2O3 injection only, 15 mg i.v. qd for 14-21 days and was repeated after 2 weeks., Results: The overall response rate was 15.2%, 13.8% in primary liver cancer (PR 4, NC 21 and PD 4). It was 25.0% in gallbladder cancer (CR 1, NC 2, PD 1). The major side reactions were mild bone marrow suppression and hepatic functional damage., Conclusion: As2O3 injection is effective in treating primary liver and gallbladder cancer with mild side reactions. It is worth studying in the future.

Objective: To observe the effectiveness of arsenic trioxide (As(2)O(3)) in the treatment of acute promyelocytic leukemia (APL)., Methods: Data of clinical observation, seven year follow-up survey were analysed with American SAS system software, concentration of arsenic in cerebrospinal fluid (CSF) was determined by atomic absorbing spectrum., Results: The complete remission (CR) and effectiveness rates were 87.9% and 94.4% for the previously untreated group; 60.0% and 65.0% for the relapsed in As(2)O(3) maintenance treatment group; 69.5% and 84.8% for the relapsed in other than As(2)O(3) maintenance treatment group; and 48.7% and 94.1% for the refractory group, respectively. In the previously untreated group, the relapse rate at 3 years after CR was 26.7%. The probability of survival in 136 follow-up survey patients was 92.0% and 76.7% at 5 years and 7 years, respectively. There were mild side effects. Central nervous system leukemia (CNSL) occurred in 138 out of 412 cases in 6 years, including some refractory leukemia, extramedullary residual leukemia and extramedullary relapse. Prophylactic intrathecal injection could reduce the incidence rate of CNSL. Determination of arsenic concentration indicated that it was difficult for arsenic to penetrate the blood-brain barrier., Conclusion: The CR rate and long-term survival are high and the relapse rate is low in APL patients treated with As(2)O(3). There is no cross-resistance between ATRA and As(2)O(3) and other chemotherapeutic agents. As(2)O(3)-resistance occurs scarcely. It can also be used in maintenance treatment.

Objective: To obtain further knowledge on the effect, mechanism and toxic side-effect of Ailing No. I (AL), a preparation of As2O3, in treating acute promyelocytic leukemia (APL)., Methods: AL was used in induction and consolidation treatment of 62 cases of APL, the effect of treatment and the changes of clinical symptoms, peripheral blood and bone marrow pictures, T-lymphocyte subset, and immunofunctions of patients after treatment were observed., Results: Twenty-seven cases out of the 31 patients who received induction treatment got complete remission (CR), the CR rate being 87.1%. Of the 31 cases who received consolidation treatment, the longest remission period was 37 months, and 7 cases relapsed within one month to 2 years. Peripheral white blood cell count raised after one week but lowered after 4 weeks of induction treatment, but in receiving consolidation treatment, it started to lower after one week and raised after 4 weeks of treatment. No obvious change on hemoglobin level was observed. Platelet count significantly increased after treatment. The treatment showed no obvious inhibition on bone marrow. The T-lymphocyte subsets and immunoglobulin level were changed insignificantly after treatment. Various side-effects were shown clinically, particularly those digestive tract involved symptoms were prominent, and liver damage was shown in a certain degree., Conclusion: AL has good and protracted effect in treating APL with high CR rate, the mechanism may be related with its cytotoxicity and action of differentiation induction.

Objective: To compare the therapeutic effects and reactions of intra venous arsenic trioxide and all-trans retinoic acid in treating patients with acute promyelocytic leukemia (APL)., Methods: 75 cases of APL were randomized either to arsenic trioxide (37) or to all-trans retinoic acid (38). The rates of complete remission (CR), disease free survival (DFS) and side effects were observed., Results: In the two groups of patients with APL, the rate of CR was 86.4% and 84.2%. There was also no significant difference in the rate of DSF phase of CR (P > 0.05). The side effects of these two medications in therapeutic dose were mild and there was no cross resistance between them., Conclusion: Arsenic trioxide can lead to apoptosis of leukemic cells and might be a new promising drug to induce differentiation.

Objective: In order to study the pharmacokinetics and metabolism of arsenic trioxide (As22O3), and its major side effects., Methods: The clinical pharmacokinetics of intravenous As2O3 in 8 relapsed acute promyelocytic leukemia (APL) patients were studied by Gas-phase chromotography., Results: (1) After 2 hour intravenous drips of 10mg As2O3, drug plasma maximal concentration (Cpmax) was 0.94 +/- 0.37mg/L(x +/- s), time to peak concentration (Tp) was 4hrs, T1/2 alpha and T1/2beta were 0.89 +/- 0.29hrs and 12.13 +/- 3.31hrs, respectively, apparent volume of distribution (Vc) was 3.83 +/- 0.45L, system clearance (CLs) was 1.43 +/- 0.17L/h and area under curve (AUC) was 7.25 +/- 0.97mg x h/L. Importantly, the continuous administration of As2O3 did not alter the pharmacokinetic behaviors. (2) During As2O3 therapy, 24-hour arsenic content in urine accounted for 1%-8% of the total dose (10mg) per day. And it decreased gradually after drug withdrawal. (3) Arsenic contents in nail and hair were increased continuously during As2O3 therapy. The peak concentrations could be five to seven-fold higher than that pre-treatment. It also decreased gradually after drug with drawal., Conclusion: As2O3 is a relatively safe and effective drug in the treatment of APL patients, in spite of certain accumulation in some tissues.