CARCINOGENICITY OF ARSENIC COMPOUNDS
There is limited evidence for the carcinogenicity of arsenic and the following arsenic compounds in experimental animals: arsenic pentoxide , arsenic trioxide , calcium arsenate , calcium arsenite (1:1) , calcium arsenite (2:1) , calcium arsenite (2:3) , disodium hydrogen arsenate , lead arsenate , potassium arsenate , potassium arsenite , sodium arsenate , and sodium arsenite
PROPERTIES
Arsenic and certain arsenic compounds occur in crystalline, powder, amorphous, or vitreous forms. Elemental arsenic is not soluble in water; calcium arsenate, and calcium arsenites (1:1), (2:1), and (2:3) are sparingly soluble in water; the remaining arsenicals are soluble in water. Arsenic pentoxide, potassium arsenite, and the three sodium salts are soluble in ethanol. Arsenic, arsenic pentoxide, arsenic trioxide, the calcium arsenites, lead arsenate, and potassium arsenate are soluble in various acids. When heated to decomposition, arsenic compounds emit toxic arsenic fumes.
USES
The estimated end-use distribution of arsenic in 1990 was 70% in wood preservatives, 22% in agricultural chemicals (principally herbicides and desiccants), 4% in glass, 2% in nonferrous alloys and 2% in other uses
Metallic arsenic was used in nonferrous alloys and in the electronics industry for semiconductor materials.
Calcium arsenate is used as an insecticide on cotton and against certain soil insects, as an herbicide for treating turf and lawns to control weeds, and as a pesticide on fruits and vegetables. Sodium arsenate is used in ant killers and in animal dips as an insecticide. Sodium arsenite is used in low percentages in herbicides for ant control and weed control, for destroying trees and stumps, in animal dips, in pesticide baits, and for soil treatment against termites. Although there is no present commercial use for calcium arsenite (1:1), it was formerly used as an insecticide, pesticide, and molluscicide. Lead arsenate was originally a part of insecticide formulations, though this use is currently negligible.
Arsenic, arsenic trioxide, lead arsenate, and potassium arsenite are used in various medicines, mostly veterinary. Formerly, disodium hydrogen arsenate was also used in this capacity. Potassium arsenite as Fowler’s solution is a hematinic used as a temporary medication for the treatment of myelogenous leukemia and certain skin lesions.
EXPOSURE AND HAZARDS
The primary routes of potential human exposure to arsenic and certain arsenic compounds are inhalation, ingestion, and dermal contact.Higher than average worker exposure may occur during the smelting of ores containing arsenic, during pesticide application, and wood preservation.Direct consumer exposure to arsenic and arsenic compounds may occur through consumption of foods.Additionally, the general population is potentially exposed to arsenic compounds through air emissions from pesticide manufacturing facilities, smelters, cotton gins, glass manufacturing operations, cigarette tobacco, burning of fossil fuels, and other sources.There is sufficient evidence for the carcinogenicity of inorganic arsenic compounds in humans.Many cases of skin cancer have been reported among people exposed to arsenic through medical treatment with inorganic trivalent arsenic compounds.An almost tenfold increase in the incidence of lung cancer was found in workers most heavily exposed to arsenic, and relatively clear dose-response relationships have been obtained with regard to cumulative exposure.
CARCINOGENICITY OF ANALGESIC MIXTURES CONTAINING PHENACETIN
There is limited evidence for the carcinogenicity of analgesic mixtures containing phenacetin.
PROPERTIES
The variety of substances and mixtures precludes a concise description of properties. Various pharmacopeias give specifications for analgesic mixtures containing phenacetin. Grades available before 1983 contained 98%-101%, or 94%-106% phenacetin on a dried basis with 0.03% maximum p- chloroacetanilide. Also available was a tablet containing 150 mg phenacetin, 230 mg aspirin, and 15 or 30 mg caffeine or 230 mg aspirin, 30 mg caffeine, and 8, 15, 30, or 60 mg codeine phosphate.
USE
Analgesic mixtures containing phenacetin were previously used as prescription and over-the-counter drugs for mild-to-moderate pain associated with the musculoskeletal system. Such mixtures have been used for more than 80 years
EXPOSURE
The primary routes of potential human exposure to analgesic mixtures containing phenacetin are ingestion, inhalation, and dermal contact. Potential consumer exposure could have occurred through ingestion of analgesic mixtures containing phenacetin as pharmaceuticals. Mixtures with phenacetin usually contained 150- 200 mg phenacetin . Potential occupational exposure could have occurred through inhalation and dermal contact for workers involved in manufacturing, formulating, packaging, or administering the pharmaceuticals.
When administered orally, a mixture of aspirin, phenacetin, and caffeine induced increased incidences of benign and malignant carcinomas of the urinary tract in mice and rats . A mixture of phenacetin and caffeine or phenacetin alone induced renal pelvic tumors and urinary bladder tumors in male rats. Half of the rats treated with phenacetin, phenazone, and caffeine in combination developed hepatomas.there is sufficient evidence for the carcinogenicity of analgesic mixtures containing phenacetin in humans . Many case reports have indicated that abuse of analgesic mixtures containing phenacetin induces increased incidences of papillary necrosis, adenocarcinomas of the renal parenchyma, transitional cell carcinomas or papillomas of the renal pelvis, and urinary bladder carcinomas.