Acute systemic toxicity

In selecting dosages for an acute systemic toxicity study, the same general guidelines apply as with lethality testing ... 

FIGURE 5.11. Example of a form for recording clinical observations in acute systemic toxicity studies. 

FIGURE 5.13. The design and conduct of a supplemented (or heavy ) acute systemic toxicity study. The figure illustrates the approach to such a study when it is to serve as the definitive systemic toxicity study for some period of time. 

Auletta, C. (1998). Acute systemic toxicity testing. In Handbook of Product Safety Assessment, 2nd ed. (Gad, S., Ed.). Marcel Dekker, New York. 

Gad, S., Smith, A., Cramp, A., Gavigan, F. and Derelanko, M. (1984). Innovative designs and practices for acute systemic toxicity studies. Drug Chem. Toxicol. 7 423 134. 

Ballantyne B. 1983b. Acute systemic toxicity of cyanides by topical application to the eye. J Toxicol, Cutan, Ocular Toxicol 2 119-129. 

Sulfur mustard is a known human carcinogen, and some of its degradation products may also be carcinogenic (IOM, 1993). Sulfur mustard acts as a vesicant or blister agent and shows acute systemic toxicity in addition to its effects on skin, eyes, and the respiratory tract. 

Irritation Sensitization Acute systemic toxicity Subchronic toxicity Local tolerance... 

Ekwall, B. et al. 1998. MEIC evaluation of acute systemic toxicity VI prediction of human toxicity by rodent LDj0 values and results from 61 in vitro methods. ATLA 26, 617-658. 

HamdoukM. PPD nephrotoxicity. In Paraphenylene diamine (Hair Dye) Acute Systemic toxicity.Thesis for MMed Sci in Nephrology, Sheffield Kidney Institute, UK. 2001, p. 34-47. 

Botham PA (2004) Acute systemic toxicity - Prospects for tiered testing strategies. Toxicology In Vitro 18 227-230. 

Tolnaftate is ineffective when administered by oral and parenteral routes (13). Therefore, it is administered only by topical route, and no reports on its pharmacokinetics and systemic metabolism have been documented. The LD50 of this drug in different animals is shown in Table 6 (4). In dogs, no toxicity was observed when a massive dose (14 g/kg) was administered orally, and in rabbits, no sensitization or irritation reaction was observed when 1% (w/v) tolnaftate solution was applied topically for 20-90 days (14). Results of this study also revealed that tolnaftate is not absorbed percutaneously. The toxicity of tolnaftate to man on topical application or by an oral administration is virtually negligible (13). Subtotal body inunction (application to 90% of the body surfaces) of 1% w/v tolnaftate solution for 7 days did not show any acute systemic toxicity (16). 

Gennari A, van den Berghe C, Casati S, Castell J, Clemedson C, Coecke S et al (2004) Strategies to replace in vivo acute systemic toxicity testing. The report and recommendations of ECVAM Workshop 50. Altern Lab Anim 32 437 59... 

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