Toxicity screening data

Lipnick R.L., Johnson, D.E., Gilford, J.H., Bickings, C.H. and Newsome, L.D. (1985) Comparison of fish toxicity screening data for 55 alcohols with the quantitiative structure-activity relationship predictions of minimum toxicity for nonreactive nonelectrolyte organic compounds. Environ. Toxicol. Chem., 4, 281-296. 

Lipnick, R. L., Bickings, C. K., Johnson, D. E. and Eastmond, D. A. (1986) Comparison of QSAR predictions with fish toxicity screening data for 110 phenols, in Aquatic Toxicology and Hazard Assessments (eds R. C. Bahner and D. J. Hansen), STP 891, ASTM, Philadelphia, PA. 

Newsome, L.D., Johnson, D.E., Cannon, D.J. and Lipnick, R.L. 1987. Comparison.of fish toxicity screening data and QSAR predictions for 48 aniline derivatives. In QSAR in Environmental Toxicology - II, Kaiser, K.L.E. (Ed.), D. Reidel Publ. Co., Dordrecht, Holland, pp. 231-250. 

COMPARISON OF FISH TOXICITY SCREENING DATA AND OSAR PREDICTIONS FOR 48 ANILINE DERIVATIVES... 

Fish toxicity screening data were obtained from four studies carried out by the U.S. Fish and Wildlife Service (McPhee and Ruelle 1969 Applegate et al. 1957 Hollis and Lennon 1954 Wood 1954). A systematic hand search of these screening data revealed that a total of 48 tested compounds met the above defined chemical structure criteria. Data were reported on tests at 0.1,1,5, and 10 mg L on up to nine species of freshwater fishes. For each test, one or two specimens per species were employed, and toxicity was reported as time to sickness or time to death within a 24-hr test duration. A typical example is shown in TABLE 1. 

TABLE 1 Toxicity screening data from three sources used in this study, shown as exampie, for4-chloro-2-nitro-aniline (compound 28). 

Ehrlichmann, H. Manh, B. Dott, W. Eisentraeger, A. Development of a miniaturized Salmonella typhimurium reversion test with kinetic data acquisition. In New Microbiotests for Routine Toxicity Screening and Biomonitoring Persoone, G., Janssen, C., De Coen, W., Eds. Kluwer Academic/ Plenum Publishers New York, 2000 503-510. 

Table 4 Industry Profile of Toxic and Classical Pollutant Loadings, Verification, and Screening Data (Toxic Pollutants Kg/kkg)... 

Similar criteria apply when evaluating data obtained from the combined repeated dose toxicity study with the reproductive/developmental toxicity screening test. 

Sipes NS, Martin MT, Reif DM, Kleinstreuer NC, Judson RS, Singh AV, Chandler KJ, Dix DJ, Kavlock RJ, Knudsen TB (2011) Predictive models of prenatal developmental toxicity from ToxCast high-throughput screening data. Toxicol Sci 124 109-127... 

RL SOP No. 70-3, dated June 1, 1967, describes methods used at Edgewood for searching for and selecting toxic chemicals. Some of the details In connection with exposure of human volunteers to experimental irritant chemicals are described. Human volunteers were exposed to compounds after review of animal screening data and approval by committees based on a conclusion that the experimental chemicals were safe for human use. Generally, two volunteers were exposed to each substance. Subjects were exposed in a wind tunnel at an airspeed of 5 mph and were asked to resist leaving the test atmosphere (up to 1 min) until exposure was unbearable. 

A toxicity screening in late 1985 compared six compounds, including BY 319 and pantoprazole. The results for pantoprazole were very promising. In a four-week toxicity study in early 1986, pantoprazole displayed the most promising data from the series of dimethoxy pyridine compounds. Based on the various animal models, pantoprazole was found to be approximately equipotent to omeprazole [37b], much more stable at neutral and weakly acidic pH, and displayed higher selectivity in enzyme models (pantoprazole is more selective to the H+/K+- as opposed to the Na+/K+-ATPase than omeprazole). Pantoprazole was not the only possible candidate compound at this time. Smith Kline French also had a potential candidate compound, SK F95601 (see Fig. 3.7), which was a 4-amino-3-chloropyridine compound [38]. 

The studies are designed using the NTP s Short-Term Reproductive and Developmental Toxicity Screen protocol (M.W. Harris et al. 1992). They are designed to provide preliminary data on the reproductive and developmental toxicity of chemicals about which little or no data exist. The results can be used to select chemicals for further study, to delineate the relative toxicities of structurally related chemicals, and to identify the proper dose range for subsequent toxicity studies. 

The role of methadone and opiates in accidental overdose deaths in New York City has been investigated using data from the Office of Chief Medical Examiner of all accidental drug overdose deaths between 1990 and 1998 (51). There were 7451 overdose deaths in all during this period, of which 1024 were methadone-induced, 4627 were heroin-induced, and 408 were attributable to both. Thus, 70% of the deaths from accidental overdose were due to opiates. Co-variates significantly associated with methadone-induced deaths were female sex, older age, and absence of cocaine, heroin, cannabis, and alcohol in toxic screens. Co-variates associated with heroin overdose were male sex, Caucasian or Hispanic ethnicity, younger age, and the absence of cocaine and methadone and the presence of cannabis and alcohol in toxic screens. 

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