Lead and arsenic are absorbed following inhalation, oral, and dermal exposure. Arsenic is then distributed throughout the body, where it is reduced into arsenite if necessary, then methylated into monomethylarsenic (MMA) and dimethylarsenic acid (DMA) by arsenite methyltransferase. Arsenic and its metabolites are primarily excreted in the urine. Arsenic is known to induce the metal-binding protein metallothionein, which decreases the toxic effects of arsenic and other metals by binding them and making them biologically inactive, as well as acting as an antioxidant. Lead is distributed mainly to the bones and red blood cells. In the blood lead may be found bound to serum albumin or the metal-binding protein metallothionein. Organic lead is metabolized by cytochrome P-450 enzymes, whereas inorganic lead forms complexes with delta-aminolevulinic acid dehydratase. Lead is excreted mainly in the urine and faeces. (L136, L20)
IDENTIFICATION AND USE: Lead arsenate is white, heavy powder. It is not registered for current pesticide use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses. Outside USA: Used on fruit trees, vegetables, rubber, coffee, coca, grapefruit, turf treatment. HUMAN EXPOSURE AND TOXICITY: Confirmed human carcinogen. Skin contact can cause burning sensation, itching and rash. Lead arsenate causes inflammation of mucous membranes and skin. Peripheral neuropathy has been observed following acute, subacute, or chronic exposures to the arsenic compounds, eg, in the course of agricultural applications of lead arsenate insecticide sprays. Two cases of lead arsenate polyneuropathy are described in two farmers. It was a neuropathy of the radial nerve associated with signs of peripheral impairment of the lower limbs with pains and paresthesias. Abdominal colic, arterial hypertension, anemia and signs of renal impairment were also present. Cutaneous manifestations due to arsenic were generally recognized as follows: diffuse pigmentation appears at first in one to two years after exposure to arsenic, then punctate hyperkeratotic lesions appear mainly on the palms and soles, and Bowen's lesions occur after several years or more. Lead arsenate used in an insecticidal spray was alleged by two patients to have caused conjunctival injury, in one resembling pemphigus. The concurrence of arsenicism and lung cancer was observed in post mortem studies of those vineyard workers who showed cutaneous stigmata of arsenic toxicity at death: lung cancer occurred in 12 out of 27 men autopsied and liver hemangioendothelioma in two. The International Agency for Research on Cancer (IARC) concluded that there was sufficient evidence that inorganic arsenic compounds, including lead arsenate, are human skin and lung carcinogens. ANIMAL STUDIES: Following repeated doses, convulsions and paralysis were observed in dogs. Rats given dietary lead arsenate at 10 mg/day for 2 yr (equivalent to 40 mg/kg/day during adulthood) showed an increase in mortality compared to controls. Rats developed nephropathy and anemia. Lead arsenate poisoning was diagnosed in 2 beef heifers and was suspected in 6 other cattle from the same herd that had died previously and were not examined. Clinical signs in affected cattle included staggering, dehydration, hemorrhage, acidemia, and shock. Five adult horses presented with acute clinical signs of watery diarrhea, excessive salivation, muscle tremors, ataxia, and depression. Four died within 24 hr and the fifth was euthanatized approximately 48 hr after onset of clinical signs. Necropsy finds in two of the horses included hyperemia of gastric mucosa, intestines filled with green to black watery fluid, and multifocal to coalescing, hemorrhagic 1.0-2.0-cm-diameter ulcers of the mucosa of the cecum and large colon. ECOTOXICITY STUDIES: A study reported/ that apple trees growing in soil contaminated from the earlier use of lead arsenate insecticide (300 mg As(V)/kg) were stunted and had badly stunted rootlets that were sparsely mycorrhizal. Trees growing in the same area in soil at < 50 mg As/kg showed healthy growth and vigorous rootlets that were intensely mycorrhizal.
Arsenic and its metabolites disrupt ATP production through several mechanisms. At the level of the citric acid cycle, arsenic inhibits pyruvate dehydrogenase and by competing with phosphate it uncouples oxidative phosphorylation, thus inhibiting energy-linked reduction of NAD+, mitochondrial respiration, and ATP synthesis. Hydrogen peroxide production is also increased, which might form reactive oxygen species and oxidative stress. Arsenic's carginogenicity is influenced by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests. The binding of other arsenic protein targets may also cause altered DNA repair enzyme activity, altered DNA methylation patterns and cell proliferation. Lead mimics other biologically important metals, such as zinc, calcium, and iron, competing as cofactors for many of their respective enzymatic reactions. For example, lead has been shown to competitively inhibit calcium's binding of calmodulin, interferring with neurotransmitter release. It exhibits similar competitive inhibition at the NMDA receptor and protein kinase C, which impairs brain microvascular formation and function, as well as alters the blood-brain barrier. Lead also affects the nervous system by impairing regulation of dopamine synthesis and blocking evoked release of acetylcholine. However, it's main mechanism of action occurs by inhibiting delta-aminolevulinic acid dehydratase, an enzyme vital in the biosynthesis of heme, which is a necesssary cofactor of hemoglobin. (T1, T4, A17, A20, A22, L136)
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/
Classification-: A; human carcinogen. Basis-Based on sufficient evidence from human data. An increased lung cancer mortality was observed in multiple human populations exposed primarily through inhalation. Also, increased mortality from multiple internal organ cancers (liver, kidney, lung, and bladder) and an increased incidence of skin cancer were observed in populations consuming drinking water high in inorganic arsenic. /Inorganic Arsenic/ /Based on former classification system/
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/
A1: Confirmed human carcinogen. /Arsenic and inorganic compounds, as As/
... Lead arsenate /was/ ... cleared slowly, indicating that the rate of absorption may be lower /since/ the inhaled arsenic is in a highly insoluble form.
After exposure to ... arsenate, most arsenic is cleared from the blood. ... In humans as well as in most animal species, exposure to ... arsenate leads to an initial accumulation in the liver, kidneys, and lungs. /Arsenate/
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
高度不溶性形态（例如，硫化砷、铅砷酸盐）的砷吸收率远低于通过口服和吸入途径的更可溶性形态。
The rate of absorption of arsenic in highly insoluble forms (e.g., arsenic sulfide, lead arsenate) is much lower than that of more soluble forms via both oral and inhalation routes.
/In rabbits/, as in humans, when highly insoluble arsenic compounds are administered (arsenic trisulfide, lead arsenate), gastrointestinal absorption is reduced 20-30%.
