Safety factors assessment

This is an average value of metal erosion during the length of service and may vary with soil conditions. In coastal areas, for instance, where the subsoil water is saline, erosion of metal would be much more rapid and a further safety factor must be considered. Field experience will be a better guide to assess this. 

In view of the above adverse effects a safety factor should be applied where flammability is assessed using flash point. For pure liquids in containers the vapor should be considered potentially flammable if the liquid temperature is upward of at least 5°C below the reported flash point. For mixtures whose composition is less certain, such as petroleum mixtures, the safety factor should be about 15°C relative to the flash point [55]. Where combinations of adverse effects are identified the safety factors should be increased accordingly. A simple but very conservative approach is to assume that all liquids having a flash point <141°F may produce a flammable atmosphere under some ambient conditions, even where no mist or froth production is involved. A more practical approach is to assume that liquids handled in air at least 5-15°C below their closed cup flash points will not present ignition risks unless... 

In risk characterization, step four, the human exposure situation is compared to the toxicity data from animal studies, and often a safety -margin approach is utilized. The safety margin is based on a knowledge of uncertainties and individual variation in sensitivity of animals and humans to the effects of chemical compounds. Usually one assumes that humans are more sensitive than experimental animals to the effects of chemicals. For this reason, a safety margin is often used. This margin contains two factors, differences in biotransformation within a species (human), usually 10, and differences in the sensitivity between species (e.g., rat vs. human), usually also 10. The safety factor which takes into consideration interindividual differences within the human population predominately indicates differences in biotransformation, but sensitivity to effects of chemicals is also taken into consideration (e.g., safety faaor of 4 for biotransformation and 2.5 for sensitivity 4 x 2.5 = 10). For example, if the lowest dose that does not cause any toxicity to rodents, rats, or mice, i.e., the no-ob-servable-adverse-effect level (NOAEL) is 100 mg/kg, this dose is divided by the safety factor of 100. The safe dose level for humans would be then 1 mg/kg. Occasionally, a NOAEL is not found, and one has to use the lowest-observable-adverse-effect level (LOAEL) in safety assessment. In this situation, often an additional un-... 

The easiest means for assessing occupational exposure hazards associated with materials used in a process is through the use of Permissible or Occupational Exposure Limits (OEL or PEL) which go by a variety of names for example, TLV (U.S. - American Conference of Government Industrial Hygienists), MAK (Germany), or individual company established values. Occupational exposure limits are usually set based on a combination of the inherent toxicological hazard of a chemical and a series of safety factors such as intraspecies variability in test results, nature and severity of the effect, adequacy and quality of... 

This gives an example of fate modeling in which the risks of an insect growth inhibitor, CGA-72662, in aquatic environments were assessed using a combination of the SWRRB and EXAMS mathematical models.. Runoff of CGA-72662 from agricultural watersheds was estimated using the SWRRB model. The runoff data were then used to estimate the loading of CGA-72662 into the EXAMS model for aquatic environments. EXAMS was used to estimate the maximum concentrations of CGA-72662 that would occur in various compartments of the defined ponds and lakes. The maximum expected environmental concentrations of CGA-72662 in water were then compared with acute and chronic toxicity data for CGA-72662 in fish and aquatic invertebrates in order to establish a safety factor for CGA-72662 in aquatic environments. 

Aquatic safety factors ranged from 5.5 X 107 for rainbow trout in ponds to 9.3 X 108 for daphnia in lakes. These data emphasize that exposure levels of CGA-72662 are low and must be taken into account for a risk assessment. Although the persistence of CGA-72662 in eutrophic lakes is relatively long, the exposure is extremely low and of no environmental consequence. Overall, use of SWRRB runoff and EXAMS models show CGA-72662 to be very safe in aquatic habitats when used on vegetables in Florida muck soil. 

The need for special facilities for work involving neutron activation analysis and radiochemical measurements has been referred to above in Section 4.3.6. Other safety factors may also influence your choice of method. For example, you may wish to avoid the use of methods which require toxic solvents, such as benzene and certain chlorinated hydrocarbons, or toxic reagents, such as potassium cyanide, if alternative procedures are available. Where Statutory Methods have to be used, there may be no alternative. In such cases, it is essential that staff are fully aware of the hazards involved and are properly supervised. Whatever method is used, the appropriate safety assessment must be carried out before the work is started. Procedures should be in place to ensure that the required safety protocols are followed and that everyone is aware of legislative requirements. 

Penninks108 assessed the evaluation of a safety factor to determine a Tolerable Daily Intake (TDI) value for the environmental contaminant bis(tributyltin)oxide (TBTO). The... 

A governing principle of pharmaceutical safety assessment is the determination of safety factors the ratio between the therapeutic dose (that which achieves the desired therapeutic effect) and the highest dose which evokes no toxicity. This grows yet more complex (but has less uncertainty) if one bases these ratios on plasma levels rather than administered doses. Traditionally based on beliefs as to differences of species sensitivity, it has been held that a minimum of a five-fold (5X) safety factor should be observed based on toxicity findings in nonrodents and a ten-fold (10X) based on rodents. 

The systematic evaluation of substance properties and predictable or actual exposure patterns over the entire life-time of a substance within the scope of risk assessment is as yet a relatively recent instrument, for which harmonised scientific rales were created in the EU for the first time in 1997 in the form of the Technical Guidance Documents (TGD). An essential element in this range of instruments is how to deal with shortcomings in knowledge. Wherever information is missing, standardised worst-case scenarios are conceived taking into account appropriate safety factors . If under these worst-case assumptions a rele-... 

Related terms Assessment Factor, Safety Factor. 

The question of an extra assessment factor in the hazard and risk assessment for chemicals of concern for children is specifically addressed in Section 5.2.1.13. The U.S. Food Quality Protection Act (FQPA) (US-EPA 1996) directed the US-EPA to apply an extra safety factor of 10 in assessing the risks of pesticides to infants and children. The US-EPA (2002) noted the overlap of areas covered by the FQPA factor and those addressed by the traditional UFs, and it was concluded that an additional UF (children-specific) is not needed in the setting of reference values because the currently available UFs (interspecies, intraspecies, LQAEL-to-NOAEL, subchronic-to-chronic, and database-deficiency) were considered sufficient to account for uncertainties in the database from which the reference values are derived. Renwick et al. (2000) concluded that the available data did not provide a scientific rationale for an additional 10-fold UF for infants and children and pointed out that when adequate reproduction, multigeneration, or developmental studies are conducted, there will be no need for an additional 10-fold factor. 

Dome, J.L. and A.G. Renwick. 2005. The refinement of uncertainty/safety factors in risk assessment by the incorporation of data on toxicokinetic variability in humans. Toxicol. Sci. 86 20-26. 

Gaylor, D.W., R.L. Kodell, J.J. Chen, and D. Krewski. 1999. A unified approach to risk assessment for cancer and noncancer endpoints based on benchmark doses and uncertainty/safety factors. Regul. Toxicol. Pharmacol. 29 151-157. 

There are of course many mathematically complex ways to perform a risk assessment, but first key questions about the biological data must be resolved. The most sensitive endpoint must be defined along with relevant toxicity and dose-response data. A standard risk assessment approach that is often used is the so-called divide by 10 rule . Dividing the dose by 10 applies a safety factor to ensure that even the most sensitive individuals are protected. Animal studies are typically used to establish a dose-response curve and the most sensitive endpoint. From the dose-response curve a NOAEL dose or no observed adverse effect level is derived. This is the dose at which there appears to be no adverse effects in the animal studies at a particular endpoint, which could be cancer, liver damage, or a neuro-behavioral effect. This dose is then divided by 10 if the animal data are in any way thought to be inadequate. For example, there may be a great deal of variability, or there were adverse effects at the lowest dose, or there were only tests of short-term exposure to the chemical. An additional factor of 10 is used when extrapolating from animals to humans. Last, a factor of 10 is used to account for variability in the human population or to account for sensitive individuals such as children or the elderly. The final number is the reference dose (RfD) or acceptable daily intake (ADI). This process is summarized below. 

Safety factors are typically used in a risk assessment to define an acceptable dose for food additives and pesticides. It is obviously very important to ensure that an artificial sweetener such as aspartame, which is commonly used in artificially sweetened drinks, has a large margin of safety. All age groups, as well as pregnant women, consume artificial sweeteners, so they must have a large margin of safety. Some factors to consider are given in Table 19.1. 

The most common methods for dealing with variability and uncertainty in the past have been the use of conservative assumptions, safety factors, and assessment scenarios. Each of these approaches has limitations that may often lead to inappropriate decisions. 

Often, the basis for safety factors is obscure and/or arbitrary. They are typically based on order of magnitude decisions, for example, determining a safe concentration and dividing it by 10. It may not be clear which sources of uncertainty they are intended to address. Even when they have been based on an explicit assessment of uncertainty, this probably will not have included more than a few sources of uncertainty. Therefore, it is not known whether the safety factors provide an appropriate level of protection against all the uncertainties affecting the assessment. 

Screening assessments incorporate variability and uncertainty implicitly, by using worst-case assumptions and safety factors. As mentioned earlier, these have rarely been based on a quantitative analysis and may not take account of the full range of uncertainties, so in principle they should be reviewed to determine whether they provide adequate margins of safety. 

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