Toxicity systemic

Cr(VI) compounds are corrosive as a result of their acidity and oxidizing potential. Oral, pulmonary, and dermal exposure to Cr(VI) may involve local irritation and corrosive action. Dermal irritation with ulceration can lead to systemic uptake of chromium, but this is an extreme situation. Perforation of the nasal septum, formerly common in industries using chromium, is rarely seen today. Dermal contact can also cause delayed sensitization and allergic dermatitis Cr(VI) appears to be more active than Cr(III) in this regard. These actions of Cr(VI) are local, not systemic, and do not involve any consideration of chromium kinetics. 

Apart from their localized toxic actions, Cr(VI) compounds are nephrotoxic in humans (Goyer 1990) and animals (Gumbleton and Nicholls 1988) 

It has been suggested that there may be a threshold for Cr(VI)-related renal tubular damage (Franchini and Murn 1988). Indeed, the rapidity and ubiquity of Cr(VI) reduction processes have suggested to some investigators the existence of a threshold for Cr(VI) dose-response relationships in general (Petrilli and DeFlora 1988). In this view, Cr(VI) would be systemically toxic only when the capacity of the multiple mechanisms for its detoxification by reduction to Cr(III) had been exceeded. 

Cr(III) has not been shown to be systemically toxic. It has been generally understood that the absence of Cr(III) toxicity is due partly to its inability to cross membranes and thus either to be absorbed or to reach peripheral tissues in significant amounts. However, Cr(III) is now known to be capable of crossing cell and other membranes when the ligand environment is favorable (Bianchi and Levis 1988). Recently, the question has been raised whether Cr(III) may be toxic even though only very small amounts are able to penetrate into cells (Debetto and Luciani 1988). The possibility of Cr(III) toxicity remains entirely speculative at the present time. 

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Specific Local Anesthetic Agents. Clinically used local anesthetics and the methods of appHcation are summarized in Table 5. Procaine hydrochloride [51-05-8] (Novocain), introduced in 1905, is a relatively weak anesthetic having along onset and short duration of action. Its primary use is in infiltration anesthesia and differential spinal blocks. The low potency and low systemic toxicity result from rapid hydrolysis. The 4-arninobenzoic acid... 

Chloroprocaine hydrochloride [3858-89-7] is characterized by low potency, rapid onset, short duration of action, and low systemic toxicity. It is indicated for infiltration anesthesia at 1—2% and for extradural anesthesia at 2—3% when short surgical procedures are performed under regional anesthesia. Chloroprocaine may be mixed with long duration agents such as bupivacaine (22, R = n-Q [) to afford a more rapid onset and shorter duration of action than bupivacaine alone. 

Clinical use of lL-1, lL-6, and TNF- a, is limited by associated systemic toxicity. SCF seems better tolerated. It may be possible to develop derivatives of other cytokiaes that are less toxic. The synthetic nonapeptide VQGEESNDK (position 163—171 of human lL-1 P) (see Amino acids ... 

The degree to which inhaled gases, vapors, and particulates are absorbed, and hence their potential to produce systemic toxicity, depends on their solubihty in tissue fluids, any metaboHsm by lung tissue, diffusion rates, and equiUbrium state. 

The induction of systemic toxicity may involve a variety of complex interrelationships between the absorbed parent material, any conversion products, and their concentration and distribution in body tissues and fluids. The general pathway that a material may foUow after its absorption is shown schematically in Eigure 2. 

Orally in rats, the toxicity of sodium tungstate was highest, tungsten trioxide was intermediate, and ammonium tungstate [15855-70-6] lowest (59,60). In view of the degree of systemic toxicity of soluble compounds of tungsten, a threshold limit of 1 mg of tungsten per m of air is recommended. 

When iadustrial wastewaters are mixed with municipal wastes, as ia many urban systems, toxic and inhibitory materials are removed ia the pretreatment system where nutrient chemicals, eg, nitrogen and phosphoms, are added. 

Melamine ia a skin test on rabbits produced neither local irritation nor systemic toxicity. As a 10% solution ia methylceUulose, it caused no irritation ia the eyes of rabbits. Human subjects were given patch tests with melamine. No evidence of either primary irritation or sensitization was found. Such results suggest that melamine crystal may be handled ia ordinary iadustrial use without special hygienic precautions. 

ECH, and PO are absorbed through the skin and may cause systemic toxic effects. 

Inhalation toxicity does not present a hazard because of low vapor pressure. DGEBPA-based resins have been reported to cause minimal eye irritation (44). Systemic toxicity has not been noted in experiments where DGEBPA-based resins have been fed to laboratory animals. Mutagenic activity has not been shown in animals, but in vitro mutagenicity tests have yielded variable results (44). 

Carcinogenicity of DGEBPA or DGEBPA-based resins, as measured by topical appHcation, has not been shown by a majority of the studies (45). Advanced DGEBPA resins exhibit low systemic toxicity either by dermal or oral routes and inhalation of these resins is unlikely because of low volatihty. The acute oral LD q in rats has been reported to be >2000 mg/kg (46). Acute dermal studies show these materials have alow potential for absorption through the skin in acutely toxic amounts. No evidence of carcinogenicity has been found in animals or humans for advanced DGEBPA resins (47,48). 

Taking into account the low oral toxicity and the low intestinal and percutaneous absorption of alcohol sulfates and alcohol ether sulfates, the possibility of systemic toxic effects in humans is extremely unlikely [344]. 

Oral poisoning after accidental phenol ingestion has caused fulminant central nervous system depression, hepatorenal and cardiopulmonary failure [20]. No hepatorenal or central nervous system toxicities with properly performed chemical peels have been reported in the literature [21]. 

In summary, preliminary results from two animal models (rabbit and mouse) indicate that poly(N-palmitoylhydroxyproline ester) elicits a very mild, local tissue response that compares favorably with the responses observed for established biomaterials such as medical grade stainless steel or poly(lactic acid)/poly(glycolic acid) implants. At this point, additional assays need to be performed to evaluate possible allergic responses, as well as systemic toxic effects, carcinogenic, teratogenic, or mutagenic activity, and adaptive responses. 

In reviewing intraarterial infusion of microencapsulated anticancer agents and its clinical applications, Nemoto (124) concluded that this mode of treatment can be used for a wide variety of tumors, providing remarkable therapeutic effects with minimal systemic toxicity. However, 25% of the treated tumors failed to respond, which was thought to be attributable to either inadequate catheterization, inadequate dose relative to tumor size, insufficient tumor vascularity, low drug sensitivity, or a combination of these factors. More carefully designed studies will be necessary before this technique is likely to meet with widespread acceptance. 

Numerous experimental therapeutics have shown potency in vitro however, when they are tested in vivo, they often lack significant efficacy. This is often attributed to unfavorable pharmacokinetic properties and systemic toxicity, which limit the maximum tolerated dose. These limitations can be overcome by use of drug carriers. Two general types of carrier systems have been designed drug conjugation to macromolecular carriers, such as polymers and proteins and drug encapsulation in nanocarriers, such as liposomes, polymersomes and micelles. 

Berman E, Schlicht M, Moser VC, et al. 1995. A multidisciplinary approach to toxicological screening 1. Systemic toxicity. J Toxicol Environ Health 45 127-143. 

Systemic toxicity/organ Evidence of adverse effects Suggestive animal studies No basis for concern identified... 

The priority effects are carcinogenicity, mutagenicity, reproductive or developmental toxicity, endocrine disruption and neurotoxicity. Human toxicity is broader than priority effects, including acute toxicity, systemic toxicity (organ effects), immune system effects and skin/eye/respiratory damageaswellasthepriority effects. And toxicity as T includes both human toxicity and ecotoxicity. 

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