Safety ratio

A high safety ratio (the ratio of the lethal dose [estimated] to the effective dose). 

AUC and Cmax are commonly measured to identify safety ratios for new chemical entities. Since the analytical methods used for biotechnologically derived pharmaceuticals may lack specificity, a clinical marker of biological activity or efficacy may sometimes be more appropriate than exposure data. 

If the LDsofor atropine (route unspecified) is approximately 450mg and if the incapacitating dose (ID50) for intramuscular atropine is approximately 10-12 mg in the average adult,, a safety ratio of about 40 (450mg/10-12mg) would seem to be a conservative estimate. Furthermore, since BZ has a central to peripheral potency ratio greater than that of atropine, an estimate of 40 as the safety factor for BZ is probably quite conservative. 

A two-person load for rope rescue is anticipated to be 600 lbs. If firefighter standards require a safety ratio of 15 1 to use a rope for rescue, what must the minimum breaking strength of a j" piece of rescue rope be before using the rope... 

Compound Tail pinch (mg/kg) PC02 (mg/kg) Safety ratio PC02 tail pinch... 

Diphenylaminechlorarsine (DM) Diphenylaminechlorarsine (DM) (see Figure 12.9) or Adamsite are pro-emetic agents used in WWI. DM has greater toxicity than other RCAs and has been abandoned in favor of compounds with less toxicity and greater safety ratios. While toxicity is typically delayed with DM exposure, toxic signs and symptoms can occur within minutes after exposure. Systemic toxicity may also be more pronounced and prolonged. Symptoms often subside hours after exposure. Because DM is an antiquated RCA, this compound is irrelevant today and will not be discussed further. 

Values derived from estimate of the human LCtso (lower bound)/irritancy threshold (minimal effective dose). Therefore, ranges are not provided for the safety ratios... 

Have the patient populations, dose and dose regimen, and benefit/safety ratio been adequately characterized to support the conduct of the large trials that are needed to confirm efficacy and to achieve the intended clinical differentiation ... 

The pharmacological tools to detoxify arsenicals are sulphydryl reagents. The classic drug for that purpose is 2,3-dimercapto-l-propanol, dimercaprol (British antilewisite, BAL). Since this compound has side effects and a low safety ratio, new analogs with less adverse effects have been developed, e.g. dimercaptopropanesulphonate, dimercaptosuc-cinic acid and dithioerythritol . The efficiency and toxicity of these agents need to be further evaluated. 

CN is considered less than lethal or nonlethal because it has a large safety ratio. That is, its effective dose or concentration ECtfo is low compared to its lethal dose or concentration (LCtfo). In the body, CN is converted to an electrophilic metabolite. It is an SN2 alkylating agent that reacts with SH groups and other nucleophilic sites of biomolecules. Alkylation of SH-containing enzymes leads to enzyme inhibition with disruption of cellular processes. CN was found to inhibit human plasma cholinesterase via a non-SH interaction, and some of the toxic effects may be due to alkylation of SH-containing enzymes. 

These agents are considered less than lethal and non-lethal because they have a very large safety ratio. That is, their effective dose or concentration ECtso is very low compared to their lethal dose or concentration (LCt5o). 

Agent LCtso 1C50 Safety ratio (LCtso/ICso)... 

Table 5. The antidotal potency and safety ratio of oximes in nerve agent-poisoned rats... 

Convention that deal with RCAs and the legitimate use of toxic chemicals for law enforcement purposes. The SAB noted that the science related to such agents is rapidly evolving, and that results of current programmes to develop such non-lethal agents should be monitored and assessed in terms of their relevance to the Convention. However, based on past experience and the fact that many of these compounds act on the central nervous system, it appears unlikely from a scientific point of view that compounds with a sufficient safety ratio would be found. 

Clinical trials can be designed and performed to demonstrate a good benefit/safety ratio, usually in phase III. 

Therapeutic Index (Tl) Margin of safety ratio between the TD and the ED... 

Safe Medical Devices Act (SMDA), 171 safety ratio, 387 Safil,237,281 Safil Quick, 281... 

Figure 9 shows equipment for determination of critical strain. Chemicals are applied on the the test piece and the crack length after a specified time is measured. The critical strain is calculated from the equation given in Figure 9. Table 5 gives data on resistance to chosen chemicals. The higher the value of critical strain, the higher the safety ratio of chemical resistance of the material. Generally there is no danger of cracking if critical strain is above 1% but a high probability exists if critical strain is below 0.5%.

Agent Irritancy Threshold (mg/m") Estimated Human LCtSO (mgmin/m ) Safety Ratio Adverse Effects... 

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