Acute Cd toxicity

In animals, cadmium can be introduced to the body from the air, food and water and is toxic to all mammalian systems whether ingested, injected or inhaled (Kostiel, 1986). Although this technological pollutant can be extremely noxious to animals in general, it is particularly so in mammals since the metal tends to accumulate in critical soft tissues like liver and kidney. Acute Cd toxicosis may cause serious diseases, e.g. the so-called itai-itai , or even lead to death (Nogawa, 1981). 

Cadmium-induced acute testicular toxicity and testicular interstitial cell tumours in rats cmild be prevented by low-dose Cd (3.0 juM/kg subcutaneously) pre-treatment (Wahba et al. 1990). 

Brooks, K. and P. DeWildt. 2000. PS149B1 14 KDA Protein Acute Oral Toxicity Study in CD-I Mice Lab Project Number 001130. Unpublished study prepared by Dow AgroSciences LLC. 39 p. 

Why should we care about Cd as a toxic compound Not because of the rare cases of acute Cd intoxication, nor because of its health threat in an occupational context... 

Acute high-dose Cd toxicity in humans is now a rarity in Western countries. Its symptoms depend on the route of ingestion [123]. Toxicity also depends on the solubility of Cd compounds [2]. 

The blood-brain barrier (BBB) severely limits Cd access to the central nervous system. A direct toxic effect of Cd on the brain occurs only prior to BBB formation and is hence age-dependent in experimental animals [360]. The brain of newborn animals is permeable to Cd which decreases with age, probably due to increased MT expression (MT-3 in brain [361] see below) and blood brain barrier maturation [362,363]. BBB dysfunction under certain pathological conditions increases the permeability to Cd, as described in a case report following acute Cd intoxication [364]. Additionally, the choroids plexus may accumulate high levels of Cd (reviewed in [365]). Nishimura et al. [366] observed strong MT immunostaining in ependymal cells and choroid plexus epithelium in younger rats (1-3 weeks old) poisoned with Cd. Thus, the sequestration of Cd by MT may partly contribute to the high accumulation of Cd in the choroid plexus. 

Apart from symptomatic treatment, there is currently no effective clinical treatment for Cd intoxication. One approach consists of trying to eliminate Cd using metal chelators such as ethylenediamine-N,N,N ,N -tetraacetate (EDTA) given by intravenous infusion to increase its urinary excretion [438], or if toxicity is so severe that renal function is impaired, EDTA is added to the dialysate during hemodialysis [439]. However, the role of EDTA remains unclear because of the limited number of reports in the literature and because chelation therapy for Cd may increase the uptake of Cd by the kidneys and increase the risk of nephrotoxicity. Friberg and Blinder [437] therefore recommended that EDTA is contra-indicated because of its nephrotoxicity when administered in combination with Cd. In experimental systems some chelators can reduce acute Cd-induced mortality [440]. Oral dimercaptosuccinic acid (DMSA) [441,442] or calcium disodium diethylene-triaminepentaacetate (DTPA) given parenterally [443] are the most effective antidotes, provided that treatment is started very soon after Cd ingestion. 

Handy, R.D. 1993. The effect of acute exposure to dietary Cd and Cu on organ toxicant concentrations in rainbow trout, Oncorhynchus mykiss. Aquat. Toxicol. 27 1-14. 

Lin, H.C. and W.A. Dunson. 1993. The effect of salinity on the acute toxicity of cadmium to the tropical, estuarine, hermaphroditic fish, Rivulus marmoratus a comparison of Cd, Cu, and Zn tolerance with Fundulus heteroclitus. Arch. Environ. Contam. Toxicol. 25 41-47. 

Rice PJ, Drewes CD, Klubertanz TM, et al. 1997. Acute toxicity and behavioral effects of chlorpyrifos, permethrin, phenol, strychnine, and 2,4-dinitrophenol to 30-day-old Japanese Medaka (Oryzias latipes). Environ Toxicol Chem 16 696-704. 

Borzelleca JF, Hayes JR, Condie LW, et al Acute and subchronic toxicity of 2,4-dichlorophenol in CD-I mice. Fundam Appl Toxicol 5 478-486, 1985... 

Hayes JR, Condie LW, Borzelleca JF. 1986. Acute, 14-day repeated dosing, and 90-day subchronic toxicity studies of carbon tetrachloride in CD-I mice. Fund AppI Toxicol 7 454-463. 

In another acute-duration exposure using higher concentrations of HDI, groups of 4 male albino ChR-CD rats were exposed to 5, 11, 26, 27, 72, or 370 ppm HDI for 4 or 8 hours. The only pathology attributed to HDI toxicity observed at sacrifice was chronic gastritis in 2 rats exposed for 4 hours to 26 ppm HDI. 

In other acute-duration studies, groups of 4 male albino ChR-CD rats were exposed to 30 ppm HDI for 4 hours daily for 10 days over a 2-week period. A slit-shaped opacity of the cornea (clinically interpreted to be a corneal ulcer) of one eye was reported in one rat that died after exposure had ended (Haskell Laboratory 1961). In another study, male rats (strain not specified) were exposed for 6 hours to an unknown air concentration of HDI. The investigators estimated that 0.4% of the HDI in a bubbler was potentially evaporated, but total air flow through the chamber was not measured, so that it is not possible to precisely calculate the air concentration of HDI inhaled by the test animals. Animals were observed for behavioral changes for 10 days after exposure. All animals survived exposure and the 10-day observation period. The authors concluded that HDI was mildly toxic. The fumes were moderately irritating to the conjunctiva of the eye soon after the start of exposure (Mobay Corporation 1966). 

Few neurological toxicities after inhalation exposures to HDl could be identified in laboratory animals. In an acute-duration study, groups of 4 male albino ChR-CD rats were exposed to various concentrations of HDl for 4 or 8 hours. When rats were exposed to 370 ppm from a bubbler of HDl warmed to 40-50 °C, they died after 2-3 hours of exposure, with irritation and convulsions observed prior to death. However, mechanical difficulties with the exposure apparatus may have contributed other factors that might have been responsible for the convulsions and eventual death of these animals (Haskell Laboratory 1961). 

Freshwater sediments Heavy metals Hg, Pb, Cu, Ni, Zn, Mn, Fe, Cd TOC Humus compound content Sulfur and nitrogen content PAH TOC V. fischeri Microtox Basic Solid-phase Test, Microtox Acute Toxicity Basic Test) V. fischeri Daphnia magna... 

Approximately three decades ago, the U.S. government created the Registry of Toxic Effects of Chemicals (RTECS) database (www.ccohs.ca/education/asp/search rtecs.html). Initially available in book form only, it became later available on CD-ROM, from the National Institute of Occupational Safety and Health, USA, or affiliated vendors (e.g., the Canadian Center for Occupational Health and Safety [CCOHS] www.ccohs.ca). This database contains information on approximately 120,000 substances, including (where available) acute and chronic toxicity data for terrestrial organisms, primarily mammalian species, such as rats, mice, rabbits, monkeys, and humans. This database will be transferred to the private sector in the near future for maintenance. RTECS cannot be searched by structure, but by name, formula, CAS, and several other means. CCOHS provides also a website which allows limited searching of the RTECS database at ccin-foweb.ccohs.ca/rtecs/search.html, but access to data is for subscribers only. 

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