Rodent acute toxicity

RODENT ACUTE TOXICITY ALGAL BIOASSAY STATIC BIOASSAY SOIL MICROCOSM... 

Using Hybrid Descriptors for the QSIIR Modeling of Rodent Acute Toxicity. 1331... 

Using "Hybrid" Descriptors for the QSiiR Modeiing of Rodent Acute Toxicity... 

We used the cell viability qHTS data from NCGC as mentioned in the above section for the same 1,408 compounds but in 13 cell lines (Xia et al. 2008). Besides the carcinogenicity, we asked if HTS results could be of value in predicting rodent acute toxicity (Sedykh et al. in press). For this purpose, we have identified 690 of these compounds, for which rodent acute toxicity data (i.e., toxic or nontoxic) was also available. The classification fcNN QSAR modeling method was applied to these compounds using either chemical descriptors alone or as a combination of chemical and qHTS biological (hybrid) descriptors as compound features. The... 

Health and Safety Factors. Sodium metabisulfite is nonflammable, but when strongly heated it releases sulfur dioxide. The oral acute toxicity is slight and the LD q (rat, oral) is 2 g/kg. Sodium bisulfite appears to be weakly mutagenic to some bacteria, ia rodent embryos, and ia a human lymphocyte test. There is iaadequate evidence for carciaogenicity (183,343). 

Male rodents have been shown to be more susceptible to acute toxic effects of methyl parathion than females (EPA 1978e Murphy and Dubois 1958). 

Toxicological Chronic toxicity Carcinogenicity Fertility study (multi-generation) Embryotoxicity (non-rodent) Acute/subacute toxicity in 2nd species Toxicokinetics... 

Acute toxicity is usually assessed by administration of a single high dose of the test drug to rodents. Both rats and mice (male and female) are usually employed. The test material is administered by two means, one of which should represent the proposed therapeutic method... 

Toxicokinetics of PCBs in rodents were altered when administered in mixtures (de Jongh et al. 1992). PCBs 153, 156, and 169 produced biphasic elimination patterns in mice when administered in combinations, but single-phase elimination when administered alone. Elimination of all PCBs was more rapid after coadministration. Mixtures of PCBs 153 and 156 raised EROD activity and lengthened retention of each congener in liver however, a mixture of PCB 153 and 169 lowered EROD activity (de Jongh et al. 1992). Selected PCBs of low acute toxicity may increase the toxicity of compounds such as 2,3,7,8-TCDD (Bimbaum et al. 1985). Thus, PCB 153 or 157 at sublethal dosages (20 to 80 mg/kg BW) did not produce cleft palate deformities in mouse embryos. But a mixture of PCB 157 and 2,3,7,8-TCDD produced a tenfold increase in the incidence of palate deformities that were expected of 2,3,7,8-TCDD alone palate deformities did not increase with a mixture of PCB 153 and 2,3,7,8-TCDD. The widespread environmental occurrence of PCB-PCDD and PCB-PCDF combinations suggests a need for further evaluation of the mechanism of this interaction (Bimbaum et al. 1985). 

Death. Information regarding death in humans following exposure to 1,2-diphenylhydrazine by any route was not found. Some information is available on lethality of orally-administered 1,2-diphenylhydrazine in animals. This information, consisting of a gavage LDso value in fats (Marhold et al. 1968) and an unreliable 3-day dietary lethal dose in mice (Schafer and Bowles 1985), indicates that single or several oral doses of about 1000 mg/kg/day may be lethal for rodents. Based on these data, 1,2-diphenylhydrazine does not appear to be highly acutely toxic to humans he oral route. 

In rodent studies iron pentacarbonyl was found to have approximately one-third the acute toxicity of nickel carbonyl. At 33 ppm for 5.5 hours three of eight rats died at 18 ppm four of eight died after two 5.5-hour exposures. Multiple 5.5-hour exposures at 7ppm caused no apparent effects. 

In humans, 4-chloro-ort/2o-toluidine induces acute toxicity in the urinary bladder and causes methaemoglobinaemia. In rodents, 4-chloro-ort/zo-toluidine and/or its metabolites bind to macromolecules in liver cells. 

IPEC-Europe (intended clinical route)b ADME Acute toxicity (intended route) and skin sensitization. Ames, chromosome damage and micronucleus. Four weeks toxicity (2 species by intended route) Short-term use studies. Three-month toxicity (most appropriate species). Teratology (rat and rabbit). Genotoxicity assays Short-/midterm studies. Segment I reproduction. Six to nine months toxicity (rodent and nonrodent), segment III reproduction, and carcinogenicity (conditional)... 

FDA (intended Standard safety Acute toxicity (rodent and Short-term use studies Short-/midterm studies... 

Catechol is oxidized by peroxidases to the reactive intermediate benzo-1,2-quinone, which binds to protein. The acute toxicity of catechol is relatively low. In humans, the irritant action of catechol can lead to dermatitis and other dermal lesions. Chronic oral treatment of rodents causes hyperplasia of the forestomach and pyloric mucosa. 

In conclusion, recent evidence suggests that MDMA and related compounds do not deserve the widespread belief that they are harmless substances which should be legally available. They constituted a potentially serious risk for acute toxic reactions that cannot be predicted by the dose taken. The acute reactions carry with them significant mortality and morbidity while the neurotoxicity shown to occur in rodents, primates and now in man suggests that they have a potential to cause permanent brain damage. 

Acute toxicity is determined by the administration of one high dose of the product to rodents, usually rats and mice of both genders. Two delivery routes are chosen, one being that proposed for normal product use. The animals are monitored and any deaths are analyzed in detail. 

Test System (Animal) Several mammalian species are used for acute toxicity studies, but the rat is the preferred rodent species. The body weight variation in test animals should not exceed 20% of the mean weight. At least 10 rodents (5 females, 5 males) should be used at each dose level, and females should be nulliparous and nonpregnant. 

In the evaluation of toxic characteristics of any environmental chemical, determination of oral toxicity using repeated doses may be performed after obtaining initial acute toxicity data. This provides information on possible adverse effects that may arise from repeated exposures to the test chemical over a limited period of time. Although there are major similarities in the 28-day and 14-day oral toxicity studies on rodents, the main difference lies in the time over which the dose is administered and the extent of the clinical and pathologic investigations that might be necessary for the shorter period of test. 

In addition to the rodent bioassay, the aromatic amines have been studied in the shorter term test Salmonella typhimurium mutagenicity as well as in a variety of acute toxicity assays. A number of QSARs have been generated from such data. The work of Hansch in recent years has demonstrated that the comparison of the QSAR models obtained in different systems, by putting them in a wider perspective, can provide useful clues in the study of the mechanisms of action of individual chemical classes, and can give precious hints on how appropriate the specific models and parameters selected are (Hansch, 2001 Hansch et al., 2002). An exercise of the mechanistic comparison of QSARs has been performed on aromatic amines (Benigni and Passerini, 2002). The results are detailed below. 

The QSARs for the acute toxicity of the aromatic amines in a variety of other experimental systems (e.g., fathead minnow, guppy, etc.) were also considered. They were much simpler than those for bacterial mutagenicity and rodent carcinogenicity, and usually relied only on hydrophobicity these findings point to a specific mechanism of action, different from the mechanisms of genotoxic carcinogenicity (Benigni and Passerini, 2002). 

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