Toxicant, defined

A slight toxic effect ( toxic defined as negative effects on health, growth, and reproduction) of the treated receiving water on the green alga Spiropyra species as a typical representative of the P-mesosaprobic zone was observed, when the test unit was subjected to the impact of 40 ppm secondary alkanesulfonates. 

Thus the promotional index PIp is positive for promoters and negative for poisons. In the latter case the definition of PIp coincides with that of the toxicity defined by Lamy-Pitara, Bencharif and Barbier several years ago.21 In the case of pure site-blocking it is PIp=-l. Values of PI02- up to 150 and of PINas+ up to 6000 have been measured as we will see in Chapter 4. 

LD50 is an index of toxicity defined by the amount of substance killing 50% of a test population (LD = Lethal Dose). 

Finally, toxicity (defined in terms of a standard extraction procedure followed by chemical analysis for specific substances) is a characteristic of all chemicals, whether petroleum or nonpetroleum in origin. Toxic wastes are harmful or fatal when ingested or absorbed, and when such wastes are disposed of on land, the chemicals may drain (leach) from the waste and pollute groundwater. Leaching of such chemicals from contaminated soil may be particularly evident when the area is exposed to acid rain. The acidic nature of the water may impart mobility to the waste by changing the chemical character of the waste or the character of the minerals to which the waste species are adsorbed. 

Impurities that cause the greatest concern are those that are toxic, defined by the US Pharmacopeia (USP) as impurities that have significant undesirable biological activity [ 1 ], and host cell contaminants in biopharmaceuticals that have potential risks of allergic reaction or other immunopathological effects [2]. 

Developmental toxicity, defined in its widest sense to include any adverse effect on normal development either before or after birth, has become of increasing concern in recent years. Developmental toxicity can result from exposure of either parent prior to conception, from exposure of the embryo or fetus in utero or from exposure of the progeny after birth. Adverse developmental effects may be detected at any point in the life span of the organism. In addition to stmcmral abnormalities, examples of manifestations of developmental toxicity include fetal loss, altered growth, functional defects, latent onset of adult disease, early reproductive senescence, and shortened life span (WHO/IPCS 2001b). 

Phase I evaluation of CP-724714 in cancer patients is ongoing [68]. The majority of patients in this trial have breast cancer and have received trastuzumab previously. The MTD was determined to be 250 mg with the dose-hmiting toxicity defined as hyperbilirubinemia and elevated liver enzymes. No objective responses have been reported for the 20 patients evaluated to date. Thirty-five percent of patients have experienced stable disease for an imdetermined period of time. In contrast to trastuzumab, cardiomyopathy has not been observed in this trial. 

Even if there is little evidence that maternal toxicity (defined as reductions in maternal body weight) is consistently associated with major malformations, there is clear evidence that substantial reduction in maternal weight is linked with other manifestations of developmental toxicity. These manifestations include decreased fetal weights, and skeletal anomalies (e.g., wavy ribs) in rats and decreased fetal weights, post implantation loss, abortions, and skeletal defects in rabbits (e.g., unossified sternebrae, metatarsals, metacarpals, or caudal vertebrae). 

Zebrafish embryo assay results were compared to the ToxCast in vitro assay features from the predictive model of developmental toxicity (50). A majority of the features were significant between the zebrafish data and predictive models, despite the fact that the zebrafish assay did not correlate with global developmental toxicity defined by species-specific ToxRefDB data. The top 15 chemicals predicted to be developmental toxicants and bottom 15 chemicals predicted not to be developmental toxicants varied in their endpoint responses and logP values. Padilla et al. (35) noted that chemical-physical characteristics could limit the amount of chemical seen by the embryo due to poor solubility or poor uptake. This may be the reason that a majority of the bottom 15 chemicals with no zebrafish embryo activity had logP values less than 1.0. The bottom 15 chemicals with zebrafish embryo activity could almost exclusively be characterized by the negative predictors of the species-specific developmental toxicity models, which may be indicating that these predictors have differing roles between mammalian and zebrafish development. 

Eriksson P, Anakarberg E, Viberg H, et al. 2001. Neonatal exposure to toxicants defined critical period altered adult susceptibility. Neurotoxicology 22(4) 510. 

Chronic toxicity defines a specific dose or exposure level that will produce measurable, long-term toxic effects, including carcinogenicity. 

The proposed US EPA weight-of-evidence (WOE) scheme for suspect developmental toxicants defines three levels of confidence for data used to identify developmental hazards and to assess the risk of human developmental toxicity (1) definitive evidence for human developmental toxicity or for no apparent human developmental toxicity, (2) adequate evidence for potential human developmental toxicity or no apparent potential human developmental toxicity, and (3) inadequate evidence for determining potential human developmental toxicity. The scheme may require scientific judgment based on experience to weigh the implications of study design, statistical analyses, and biological significance of the data. 

Fifty-four subjects drank water contaminated with VX to find the time to incipient toxicity, defined as inhibition of erythrocyte cholinesterase activity of 70% or more (Sim etal, 1964). Doses of VX and types of water were varied. At an amount of 400 qg per 70 kg in distilled water, cholinesterase activity fell to 22% of the control activity in 1 day. With the same amount in distilled water to which tetraglycine hydroperi-odide (a water-purifying agent) was added, the mean cholinesterase activity was 17% of control... 

Two other studies did not find aminoglycosides increased the risk of amphotericin B-associated toxicity (defined as a 100% or greater increase in serum creatinine), although in one of the studies the frequency of concurrent aminoglycoside use may have been too low to identify any evidence of increased nephrotoxic risk. 

Reproduction toxicity. Reproduction toxicity defined in the EC classification embraces two independent properties ... 

Material s potential toxicity defined and precautions needed. 

Toxicity Defined in terms of a standard extraction procedure followed by chemical analysis for specific substances... 

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