Variability, acute toxicity

A QSAR for the acute toxicity of new hypoglycemic agents [48] was internally cross-validated, but used LD50 instead of log LD50 as the dependent variable, and (more seriously) used LD50 values in g kg rather than in a molar unit such as mmol kg. ... 

Phase I The preliminary studies in humans are designed to evaluate the pharmacokinetics and the acute toxicity/tolerability of the potential dmg. Usually, phase I studies are carried out in a very small population [15—40] of healthy male volunteers. Thus, the nature of the population tested and the small number of individuals involved limits the scope of pharmacogenomics to the study of genetic variability in drug metabolism. 

Intraspecies Because the species used was the most sensitive to monomethylhydrazine toxicity and the most closely related to humans, an uncertainty factor of 3 is justified. A factor of 3 was used. Although the mechanism of toxicity is uncertain and sensitivity among individuals may vary, the exposure-response relationship is steep, suggesting limited variability in the toxic response to methylhydrazine. Furthermore, it is likely that acute toxic responses are, at least initially, a function of the extreme reactivity of methylhydrazine. The interaction of the highly reactive monomethylhydrazine with tissues (e.g., pulmonary epithelium) is not likely to greatly vary among individuals. 

The available C12LAS acute toxicity data for fish indicate little intraspecies variability (Table II). For the four species tested, the 96-h LCso concentrations of C12LAS range from 1.2 mg/L for the fathead minnow Pimephales promelas (64) to 6.2 mg/L for the minnow Phoxinus phoxinus (68). Although the variety of species tested is not as broad as for the invertebrates, the available data suggest that sensitivity of fish to C12LAS is similar to that of the most sensitive invertebrates. 

Arsenic, Cobalt, Copper TT assessment of relationships between acute toxicity and various experimental variables (e.g., metal concentration in water, time of exposure, bioconcentration factor) with two fish species. F,F (Liao and Lin, 2001)... 

ICE was developed for estimating acute toxicity of chemicals to species where data are lacking. Interspecies correlations were created for 95 aquatic and terrestrial organisms using least squares regression where both variables are random (i.e., both variables are independent and subject to measurement error Asfaw et al. 2004). The correlation coefficient (r) is used to describe the linear association amongst the... 

Wik, A., Dave, G.(2006) Acute toxicity of leachates of tire wear material to Daphnia magna -variability and toxic components. Chemosphere 64 1777-1784. 

SAFETY PROFILE Variable toxicity. Thiocyanates are not normally dissociated into cyanide they have a low acute toxicity. Prolonged absorption may produce various skin eruptions, running nose, and occasionally dizziness, cramps, nausea, vomiting, and mild or severe disturbances of the nervous system. Violent reactions have occurred when mixed with chlorates, nitrates, HNO3, organic peroxides. 

Delphinium species contain complex diterpenoid alkaloids that cause acute intoxication and death in cattle (6). The alkaloids and their concentrations vary with the species and plant part involved, which causes variability in toxicity. In Delphinium consolida (larkspur) there are toxic alkaloids in the non-medicinal plant parts (root, seed, herb), but they are purportedly absent in the medicinal part (the flower). 

Acute toxicity in rats (LD i ) was determined by oral administration 200 mg/kg and by intravenous and intraperitoneal administration 18 mg/kg and 10 mg/kg respectively. Chronic toxicity by oral administration to rats gave variable results in one series of experiments 10 mg/kg daily in rats for two years show ed no toxic symptoms except a retarded weight in females. No carcinogenic effect was found. 

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