Toxicity human experimentation

Bruner LH, Carr GJ, Harbell JW, and Curren RD (2002) An investigation of new toxicity test method performance in validation studies 3. Sensitivity and specificity are not independent of prevalence or distiribution of toxicity. Human Experimental Toxicology 21 325-334. 

Hazard identification, step one, means identification of new chemicals or other factors that may cause harmful health effects. Previously, novel hazards were usually observed in case studies or after accidents or other excessive exposures, usually in occupational environments. Today, thorough toxicity studies are required on all pesticides, food additives, and drugs. New chemicals also have to be studied for their potential toxic effects. Thus, earlier hazards were in most cases identified after they had caused harmful effects in humans. Today, most chemical products have been evaluated for their toxicity with experimental animals. Therefore, hazard identification has become a preventive procedure based on safety studies conducted before a chemical compound or product reaches the market, and before individuals are exposed to it. ... 

Fisher RL, Hasal SJ, Sipes IG, et al. 1995. Comparataive metabolism and toxicity of dichlorobenzenes in Sprague-Dawley, Fischer-344 and human liver slices. Human Experimental Toxicology 14 414-421. 

An additional assessment factor, of up to 10, has been apphed in some cases where the NOAEL has been derived for a critical effect, which is considered as a severe and irreversible effect, such as teratogenicity or non-genotoxic carcinogenicity, especially if associated with a shallow dose-response relationship. The principal rationale for an additional factor for nature of toxicity has been to provide a greater margin between the exposure of any particularly susceptible humans and the dose-response curve for such toxicity in experimental animals. 

Cadmium sulfide is moderately toxic to experimental animals by aU routes of exposure. Toxicity in humans is low. It is, however, carcinogenic to humans. 

Toxic. An experimental carcinogen by inhalation. Reasonably anticipated to be a human carcinogen.4 LD50 (oral, male and female rat) 2650, 3360 mg/kg.1 No TLV.2... 

Thier, R., Lewalter, J., and Bolt, H.M., Species differences in acrylonitrile metabolism and toxicity between experimental animals and humans based on observations in human accidental poisonings, Arch. Toxicol., 14, 184-189, 2000. 

Toxicity Benzyl chloride is a severe irritant to the eyes and respiratory tract. Contact with skin may cause dermatitis, and liquid contact with the eyes produces severe irritation and may cause corneal injury.116119 Benzyl chloride is a potential agent known to cause pulmonary edema in animals and humans. Experimental studies have shown development of sarcoma in animals.1193 It is, therefore, important that workers be instructed to use and handle this chemical under proper management. 

The magnitude of human experimentation in the United States is quite substantial. Each year more than 3000 clinical trials are carried out subject to FDA regulations. Thousands more trials are carried out in other countries. Each trial involves many volunteers, and the humans who are the first to take experimental therapies often face major risks. Yet without human experiments we would not know with any degree of certainty whether potential new preventions, such as vaccines, drugs, and surgery, are safe. Even then, these therapies can prove toxic in many ways. 

The subcommittee reviewed data that came primarily from human experimental studies and from toxicity studies in various animal species. The evaluation focused on inhalation exposure studies that measured respiratory irritation and tolerance to odor. Human case studies, accident reports, and epidemiologic studies of industrial exposures were extensive but of limited use to the subcommittee because they lack quantitative exposure measurements. Controlled human experiments were most important to the subcommittee for establishing the SEALs for ammonia. There appears to be a broad range of sensitivity to ammonia s pungent odor and in irritation caused by exposures to low concentrations... 

TABLE 2-4 Human Toxicity Data, Experimental Exposure to Ammonia... 

When assessing manifestations of toxicity, evaluators might base their conclusions about relevance on the mechanism that produces a toxicological effect however, a basic default assumption is that any manifestation of reproductive or developmental toxicity is relevant to humans unless the mechanism by which it occurs is impossible in humans. For example, if a toxic effect occurs in animals through an inhibition of folic acid synthesis, that effect would not be considered relevant for humans because humans do not synthesize folic acid. It is unusual, however, to have such detailed knowledge about mechanisms of toxicity from experimental animal studies. 

SAFETY PROFILE Poison by ingestion, intraperitoneal, subcutaneous, intradermal, and intravenous routes. Human systemic effects by ingestion of very small amounts toxic psychosis. Experimental reproductive effects. When heated to decomposition it emits very toxic fumes of NOx and HCl. 

Chung HL, Tsao WC, Hsue HC, Kuo CH, Ko HY, Mo PS, Chang HY, Chuo HT, Chou WH. Hexachlorophene (G-11) as a new specific drug against clonorchiasis sinensis its efficacy and toxicity in experimental and human infection. Chin Med J (Engl) 1963 82 691-701. 

Dayan AD and Paine AJ (2001) Mechanisms of chromium toxicity, carcinogenicity and allergenicity Review of the literature from 1985 to 2000. Human Experimental Toxicology 20(9) 439—451. 

Propylene glycol has very low systemic toxicity in experimental animals and very high doses are required to determine a toxic level. Central nervous system (CNS), hematologic, hyperosmotic, and cardiovascular effects have been noted in humans and animals and high serum concentrations of propylene glycol may result in lactic acidosis and hyperosmotic changes in the blood. 

McArthur et al. (Ml) and others have demonstrated that extracts prepared by the tannic acid procedure are less toxic to experimental animals than those obtained by most other techniques including the variants of the kaolin-acetone method. Herbst et al. studied the accuracy of the tannic acid method by conducting recovery experiments involving the addition of the second International Reference Preparation for human menopausal gonadotropin (second IRP-HMG) to pools of normal male urine. They found that approximately 100% of the LH activity, but only 50% of the FSH activity, was recovered (H5). 

What are the known acute toxic effects of the product based on human exposures Initially, one might say that such information usually does not exist since our society does not condone human experimentation involving products other than drugs. Conversely, it could be argued that such information could be obtained from unplanned human exposures but that these would only occur after the product had been placed on the market. Thus, the information would not be available to the label writer at the time that it was needed. While the former statement is usually true the latter is usually not. It is the unusual product that does not have several close relatives if not a twin already in the market place. Thus, such human exposure information probably exists. One source of such information is the National Poison Center Network whose resources will be described later in this chapter. Obviously, such exposure information is undeniably superior to all others since humans form the principal audience that is to be addressed by the first aid statements. Manufacturers should make every effort to obtain such information. As previously mentioned, the sole dependency on animal studies may lead to erroneous conclusions. 

Chloroform produced embryo toxicity in experimental animals, causing a high incidence of fetal resorption and retarded fetal growth. Animal experiments indicate this compound to be carcinogenic, causing cancers in the kidney, liver, and thyroid. It is a suspected human carcinogen for which there is limited evidence. 

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