CHEMICAL SPECIATION STUDIES HAVE SHOWN THAT DIMETHYLARSINIC ACID & METHANEARSONIC ACID ARE PRIMARY FORMS OF ARSENIC PRESENT IN URINE OF HUMANS EXPOSED TO ... ARSENIC TRIOXIDE BY INHALATION.
来源:Hazardous Substances Data Bank (HSDB)
代谢
砷冶炼工人的尿液剖面显示，二甲砷酸是主要物种，其次是甲基砷、三价砷和五价砷。
Urinary profiles of arsenic smelter workers showed that dimethylarsenic acid was the major species followed by methyl arsenic, trivalent arsenic, and pentavalent arsenic.
Urinary concentrations of the four arsenic species, pentavalent (As(V)) and trivalent (As(III)) inorganic arsenic, monomethylarsonic acid (MMAA) and dimethylarsinic acid (DMAA), were followed for several days subsequent to the acute intoxication of two human subjects by arsenic trioxide and sodium orthoarsenate, respectively, in unsuccessful suicide attempts. Total arsenic concentrations ranged from 1.6 to 18.7 mg/1. The increasing predominance of the less toxic methylated species, especially dimethylarsinic acid, after 3 or 4 days supports the concept of methylation as a natural detoxification mechanism as part of an overall reduction/methylation sequence involved in the biotransformation of inorganic arsenic by the human body. However, the additional possibility of oxidation of As(III) to As(V) in vivo under extreme immediate postingestion conditions is suggested by initial high urinary As(V), As(III), monomethylarsonic acid and dimethylarsinic acid in both cases probably reflect species dependent differences in rates of direct elimination and reactivity with tissues as well as the efficiency of methylation.
Rat liver cytosol inactivates inorganic arsenic through methylation; S-adenosylmethionine is the methyl group donor and reduced glutathione is required for full activity. ... Pathway involves the formation of a monomethylated metabolite which is either rapidly further methylated into a dimethylated derivative or is spontaneously oxidized into monomethylarsinic acid. The dimethylated metabolite gives rise to dimethylarsinic acid. The first methylation reaction is rate limiting, can be stimulated by glutathione and is catalyzed by an enzyme different from that which transfers the second methyl group. The latter is sensitive to inhibition by inorganic arsenic. ... A large excess of thiol groups may prevent the methylation reactions probably by decreasing the amount of free trivalent arsenic.
Classification of carcinogenicity: 1) evidence in humans: sufficient; 2) evidence in animals: limited. Overall summary evaluation of carcinogenic risk to humans is Group 1: Carcinogenic to humans. NOTE: This evaluation applies to the group of chemicals as a whole and not necessarily to all individual chemicals within the group. /Arsenic and arsenic compounds/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
A1: 确认的人类致癌物。/砷和无机砷化合物，如As/
A1: Confirmed human carcinogen. /Arsenic and inorganic compounds, as As/
Evaluation: There is sufficient evidence in humans that arsenic in drinking-water causes cancers of the urinary bladder, lung and skin ... Overall evaluation: Arsenic in drinking-water is carcinogenic to humans (Group 1). /Arsenic in drinking water/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
... 在实验动物中，关于亚砷酸钠、砷酸钙和三氧化二砷致癌性的证据有限 ... /饮用水中的砷/
... There is limited evidence in experimental animals for the carcinogenicity of sodium arsenite, calcium arsenate and arsenic trioxide ... /Arsenic in drinking water/
◉ Summary of Use during Lactation:Most sources consider breastfeeding to be contraindicated during maternal antineoplastic drug therapy. It might be possible to breastfeed safely during intermittent therapy with an appropriate period of breastfeeding abstinence; the manufacturer recommends an abstinence period of 1 week after the last dose. Chemotherapy may adversely affect the normal microbiome and chemical makeup of breastmilk. Women who receive chemotherapy during pregnancy are more likely to have difficulty nursing their infant.
◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk:A telephone follow-up study was conducted on 74 women who received cancer chemotherapy at one center during the second or third trimester of pregnancy to determine if they were successful at breastfeeding postpartum. Only 34% of the women were able to exclusively breastfeed their infants, and 66% of the women reported experiencing breastfeeding difficulties. This was in comparison to a 91% breastfeeding success rate in 22 other mothers diagnosed during pregnancy, but not treated with chemotherapy. Other statistically significant correlations included: 1. mothers with breastfeeding difficulties had an average of 5.5 cycles of chemotherapy compared with 3.8 cycles among mothers who had no difficulties; and 2. mothers with breastfeeding difficulties received their first cycle of chemotherapy on average 3.4 weeks earlier in pregnancy. Of the 9 women who received a fluorouracil-containing regimen, 8 had breastfeeding difficulties.
BOTH HUMAN & ANIMAL DATA INDICATE THAT OVER 80% OF INGESTED DOSE OF DISSOLVED INORG TRIVALENT ARSENIC IS ABSORBED FROM GI TRACT. ... IN CASE OF ARSENIC TRIOXIDE, WHICH IS ONLY SLIGHTLY SOL IN WATER, GI ABSORPTION WILL BE DEPENDENT ON FACTORS SUCH AS PARTICLE SIZE & PH OF THE GASTRIC JUICES.
FOLLOWING DIETARY ADMIN OF 215 PPM ARSENIC IN FORM OF ... ARSENIC TRIOXIDE FOR UP TO 52 DAYS IN RATS, HIGHEST ... LEVELS ... WERE FOUND IN KIDNEYS & LIVER & RELATIVELY LOWER LEVELS IN HAIR, BRAIN, BONE, MUSCLE & SKIN. ... TRIVALENT ARSENIC ... IS CONVERTED TO ... /PENTAVALENT ARSENIC IN MAN/ WHICH IS RAPIDLY EXCRETED BY KIDNEYS.
ORAL ADMIN OF 1 MG/KG BODY WT ARSENIC AS ARSENIC TRIOXIDE TO MONKEYS RESULTED IN APPROXIMATELY 80% ABSORPTION FROM THE GUT; 75% OF THE ADMIN DOSE WAS EXCRETED WITHIN 14 DAYS, PRIMARILY IN URINE.
... MALE & ... FEMALE RATS, 21 DAYS OF AGE WERE GIVEN DIET CONTAINING 26.8 OR 215 MG/KG OF DIET ARSENIC AS ARSENIC TRIOXIDE AD LIBITUM. ... LITTERS OF FOLLOWING 3 PREGNANCIES WERE EVALUATED, AS WELL AS FIRST LITTER OF SECOND GENERATION. AMT ... FOUND IN NEWBORNS WAS LOWER IN FIRST LITTER OF FIRST GENERATION ... THAN LATER LITTERS ...
