Toxicology studies

The cost of developing a new active ingredient, however, is much more cosdy than the basic costs involved in toxicology studies, as shown in Table 3, and is likely to be 35 X 10 (13). 

No toxicological studies have been reported on the triple salt. However, because of the common confusion of this compound with potassium hydrogen monoperoxosulfate monohydrate, it is possible that the pubHshed descriptions of the toxic properties of this latter compound actually refer to the triple salt. If this is so, then the triple salt must be regarded as toxic and irritating to skin, eyes, and mucous membranes (2). 

Humans and DomesticHnimals. Data from toxicology studies are used to evaluate hazards to humans from the use of pesticides (40 CFR 158.340 and Subdivision F Guidelines). 

Biological characterization includes toxicological studies, dose relationships, routes of adininistration, identification of side effects, and absorption, distribution, metaboHsm, and excretion patterns. If the results are stiU acceptable, product formulation and dosage form are developed. The product should be pleasing to the patient and thus may contain flavoring and colorants. 

Numerous toxicological studies have been conducted on a variety of plasticizers. However, because di-(2-ethylhexyl) phthalate (DEHP) is the most widely used plasticizer and is a well-defined single substance, it is the plasticizer that has been most thoroughly investigated in terms of its toxicology and has often been considered as a model for the other phthalates (36). 

The major use of this compound is in the production of mordant and acid dyes. 2-Amino-4-nitropheno1 also has found limited use as an antioxidant and light stabilizer in butyl mbbers and as a catalyst in the manufacture of hexadiene. The compound has been shown to be a skin irritant and continuous exposure should be avoided. Toxicological studies indicate that it is nonaccumulative (162). 

In addition to being used for screening purposes for new dmg development, labeled dmgs and ligands are widely used by pharmaceutical companies for metabohc, bioavailabihty, and toxicological studies to support new dmg appHcations for FDA approval. 

Many other dihydrochalcones have been made, but most of the toxicological studies have been conducted using NHDC and thus (20) has been petitioned and allowed for use. Neohesperidin is best isolated from the bitter orange (Seville orange), but it can also be synthesized from (18) and isovanillin [621-59-0] (21) (Fig. 7) (98). 

D. M. Smith and co-workers, A Preliminary Toxicological Study of Silastic 386 Catalyst, Report LA-7367-MS, Los Alamos Scientific Laboratory, Los Alamos, N.M., une 1978. 

During the design, conducting, and evaluation of toxicology studies, there is a constant need to be aware of the numerous factors that may influence the nature, severity, and probabiUty of induction of toxic injury. Some of the more important are Hsted below. 

The review and interpretation of toxicology studies is a professional matter, requiring experience in both the laboratory conduct of such studies and the practice of appHed toxicology. Although all studies should be reviewed on a case-by-case basis, there are some general considerations to be kept in mind during the review process, described below. 

Toxicity of Chlorine Sanitizers. Chlorine-based swimming-pool and spa and hot-tub sanitizers irritate eyes, skin, and mucous membranes and must be handled with extreme care. The toxicities are as follows for chlorine gas, TLV = 1 ppm acute inhalation LC q = 137 ppm for 1 h (mouse) (75). The acute oral LD q (rats) for the Hquid and soHd chlorine sanitizers are NaOCl (100% basis) 8.9 g/kg (76), 65% Ca(OCl)2 850 mg/kg, sodium dichloroisocyanurate dihydrate 735 mg/kg, and trichloroisocyanuric acid 490 mg/kg. Cyanuric acid is essentially nontoxic based on an oral LD q > 20 g/kg in rabbits. Although, it is mildly irritating to the eye, it is not a skin irritant. A review of the toxicological studies on cyanuric acid and its chlorinated derivatives is given in ref. 77. 

Toxicological studies have demonstrated that there are no important problems with fluconazole. Therapeutic doses of fluconazole may cause enzyme induction in the Hver. This suggests that interactions with other dmgs cannot be excluded. The side effects are similar to those of itraconazole and include nausea, headache, and vertigo. Occasionally, increased Hver enzymes may be noted. Like itraconazole, fluconazole is contraindicated during pregnancy. 

Exposure to metal carbonyls can present a serious health threat. Nickel carbonyl is considered to be one of the most poisonous inorganic compounds. However, the toxicological information available on metal carbonyls is restricted to the mote common, commercially important compounds such as Ni(CO)4 and Ee(CO). Other metal carbonyls are considered potentially dangerous, especially ia the gaseous state, by analogy to nickel and iron carbonyls. Data concerning toxicological studies on a few common metal carbonyls are Hsted ia Table 6 (185). Additional toxicity data are OSHA personal exposure limits (PEL) for Ee(CO) this is 8 h at 0.1 ppm, whereas for the much more toxic Ni(CO)4 it is 8 h at 0.001 ppm, with a toxic concentration TCLq low (of 7 mg/m ) for human inhalation. 

Toxicological Studies of Uralac Powder Coating Resin andPowders, Scado B. V., ZwoUe, The Netherlands, 1979. 

Acute toxicides (LD q rats) for CA and chloroisocyanurates are CA > 5.0, SDCC 1.67, PDCC 1.22, and TCCA 0.75 (126). A review of toxicological studies on CA and its chlorinated derivatives is given in Reference 127. These studies show that the compounds are safe for use in swimming pool and spa/hot tub disinfection, sanitizing, and bleaching appHcations when handled and used as directed. 

Toxicological studies conducted on DCPD indicate that it is a moderately toxic material and, to some extent, an irritant and a narcotic. By oral administration in the rat, the LD q is 0.82 g/kg of body weight, and by skin absorption in the rabbit, the LD q is 6.72 ml,/kg. An atmospheric concentration of 2000 ppm causes death in rats exposed for a period of 4 hours. 

Physicochemical properties requked include melting/boiling point, vapor pressure, solubiUty, and flammabiUty/explosion characteristics. The toxicological studies include acute toxicity tests, oral, inhalation, and dermal skin and eye kritation skin sensiti2ation subacute toxicity, oral, inhalation, and dermal and mutagenicity tests. In vitro reverse mutation assay (Ames test) on Salmonella typhimurium and/or E.scherichia coli and mammalian cytogenic test. In vivo mouse micronucleus test. 

All preparations of enzymes intended for parenteral use are tested for safety in lower animals under the conditions anticipated in clinical trials ie, their use must be nonpyrogenic in the USP rabbit assay (255), and must be sterile. Such toxicologic studies are usually a prerequisite for approval by the FDA for the sale of such pharmaceuticals. 

Severe Chemicals for which toxicological studies report tearing of... 

Hecdth effects data come from three types of studies clinical, epidemiological, and toxicological. Clinical and epidemiological studies focus on human subjects, whereas toxicological studies are conducted on animals or simpler cellular systems. Ethical considerations limit human exposure to low levels of air poUutants which do not have irreversible effects. Table 7-1 lists the advantages and disadvantages of each type of experimental informahon. 

Compare the strengths and weaknesses of health effects information obtained from epidemiological, clinical, and toxicological studies. 

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