Predicted No-Effect Level

Risk assessment is the conventional tool for decision making on the acceptability of chemical use. It is based on predicted exposure levels, predicted no-effect levels of individual chemicals and politically defined degrees of acceptable risk. Each of these processes involves a series of value judgements and estimations. Risk assessment is therefore highly subjective. 

Risk assessment is based on hazard and exposure information and a conq)arison between a predicted no effect level (concentration) with a predicted exposure level (concentration). 

Eor the assessment of the environmental hazards, the concentration of the Predicted No-Effect Level (PNEC) has to be determined. 

In the case of some oestrogenic chemicals (that mimic the effects of the female hormone oestrogen) it has been shown that what should be added to predict the combined effect of a mixture is not the effects of the individual chemicals but their concentrations (Silva et al, 2002). This means that a substance present at a concentration at which on its own it has no oestrogenic effect will contribute to the total oestrogenic effect of a mixture containing other oestrogenic chemicals. For such substances there is in practice no real threshold concentration below which they do not have an effect. Such no-effect levels are a crucial part of chemicals risk assessment, as I will explain in Chapter 7. 

Risk assessment of chemicals does not, in practice, estimate the incidence and severity of the adverse effects likely to occur in the human population or environmental compartment due to actual or predicted exposure to a substance — the definition of risk characterization in Article 2 of Directive 93/67/EEC. The assessment process hinges on being able to say that there is a threshold below which the chemical has no adverse effects, in other words on being able to derive a no-effect level. Recent debates, discussed later, challenge the idea that there normally is such a threshold. 

REACH uses the terms derived no-effects level (DNEL) for hazards to human health and predicted no-effect concentration (PNEC) for hazards to the environment. 

The test chemical is typically administered directly into the stomach by gavage, which is a requirement of EPA and some other regulatory agencies. This method of dosing allows a precise calculation of the amount of test material received by the animal. Studies typically have three dose levels and a control group that receives the vehicle used for test material delivery. The high dose level is chosen to be one at which some maternal toxicity is known to occur, but never one that would cause more than 10% mortality. The low dose should be one at which no maternal toxicity is apparent, and the intermediate dose(s) should be chosen as a predicted low effect level. 

The Japan Soap and Detergent Association has voluntarily implemented monitoring surveys since 1994 on the concentration of surfactants in the surface layer water of rivers in Japan in order to monitor the situation of persistence of surfactants in public waters and evaluate the effects ofsurfactants on aquatic organisms [2 ]. Table 8.7 shows the measurement results of the concentrations of four surfactants regulated by the PRTR system in the major Japanese rivers during the period from June 1998 to September 2003 (mean levels and highest levels) [2]. The highest levels in the table were all lower than the predicted no-effect concentrations (PNEC) [3, 4] and therefore it was considered that the surfactants cause almost no risks to the ecosystem in the environmental waters. 

PNEC Predicted no-effect concentration or level. The maximum level (dose or concentration) that, on the basis of current knowledge, is likely to be tolerated by an organism or ecosystem without producing any adverse effect. 

Bisphenol A has been used as an inhibitor at the PVC polymerisation stage and as an antioxidant. There has been some concern regarding possible health hazards and its use has been voluntarily stopped or restricted to levels that do not exceed the predicted no effect... 

Ultimately a derived no-effect level (DNEL) (in humans) or a predicted no-effect concentration (PNEC)20 (in ecosystems) is calculated for a substance, group of substances or chemical mixture. Assessment factors (AF) - sometimes referred to as uncertainty factors or safety factors - compensate for lack of data and assumptions resulting from dose spacing and other test model parameters (adapted from [124]) ... 

Chemical risks are measured by comparing the predicted or measured exposure to the DNEL or PNEC. In risk assessment, the extent to which an exposure exceeds a DNEL or PNEC determines if a risk is deemed high or very high . If an exposure is considerably less than the no-effect level (e.g., a factor of >1000 when compared with a NOEL), the risk is generally considered insignificant (see [146]). 

Commission, exposure of humans and the environment can be considered to be adequately controlled if the Derived No Effect Levels (DNEL) or the Predicted No Effect Concentrations (PNEC) are not exceeded [199]. 

The endpoint of both EUSES and USES is a quantitative comparison per substance of the results of the effects and the exposure assessment. The latter aims at providing reasonable-worst-case results by applying unfavorable, but not unrealistic, standard exposure scenarios. The risk assessment is carried out in a stepwise procedure, starting with data input aud estimation, and further involving estimation of emissions, prediction of environmental distribution, calculation of human and environmental exposure, derivation of no-effect levels and risk... 

The use of NOECs and LOECs has been questioned as they have some major limitations. Their values depend very much on the concentrations that have been selected in the test set-up. Large concentration steps will result in a large difference between NOEC and LOEC. Moreover, poor test design (e.g. low number of replicates) will result in increased variance of effects and the acceptance of the null hypothesis. As a consequence, the toxicity of a chemical may be underestimated. Statistical measurement endpoints obtained from ecotoxicity testing may be used to derive predicted no effect concentration (PNEC) levels that are employed in ecological risk assessment for chemicals. 

Lin BL, Tokai A, Nakanishi J. 2005. Approaches for establishing predicted-no-effect concentration for population-level ecological risk assessment in the context of chemical substances management. Environ Sci Technol 39 4833 4840... 

Adverse or harmful effects will occur if measured or predicted environmental concentration (PEC) in various environmental media such as water, soil, sediment and the atmosphere is higher than predicted no effect concentrations (PNEC, or maximum tolerable concentration MTC) based on the above ecotoxicity test results. PNEC values combine the ecotoxicity data with an assessment factw (AF). Data from short-term studies in the laboratory generally need large AFs (100-KXX) are applied to the lowest L(E)C5o) data from long-term laboratory studies or ecosystem field studies need smaller AFs (usually 10 applied to the lowest no observable effect levels (NOEL). 

Such simple models need validation and for this reason ETAD is conducting in a field study to investigate some representative dyes (at manufacturing sites and dyehouses) under a project termed Pathways of Colorants to the Environment. The environmental risk posed by a colorant is a function of both its inherent ecotoxicity and the concentrations attained in the environmental compartments. Unlike other substances eg, household detergents) which are emitted continuously, dyes releases result mainly from batch processes and result in spatial and temporal peak emissions. Obviously, short-time concentrations should be compared with acute data on ecotoxicity, whereas long-tom residual concentrations need to be cranpared with chronic effect levels. Because, data on chronic effects are not often available, empirical information serves as a basis for the effects assessment, ie, the extrapolation to a Predicted No Effect Concentration (PNEC). This PNEC value is to be compared with the so-called Predicted Environmental Concentration (PEC) in order to estimate safe levels of residual dye in the environment. Since it is the dissolved state in which a dyes may become biologically available, it is the aquatic environmental compartment which is primarily addressed here. Nonetheless, some consideration of the impact of dyes on sewage and soil is also included. 

The Predicted No Effect Concentration may be derived from laboratory, field or theoretical data. Studies conducted on single species such as acute toxicity to fish (IX so) over a relatively short time scale (normally 40 or % h) and with death as the only recorded endpoint is, by itself, only of limited value in deciding whether or not a predicted environmental level of a dye is, or, is not, acceptable. Extrapolation from acute effects to chronic and ecosystems effects involves numerous uncertainties. In order to protect the ecosystem, conservative assessment factors have been introduced based on the statistical analysis of a set of data [17] for chronic exposure. The US-EPA [18] has proposed to apply a factor of KXX) for a single acute L(E)Cso value or 100 to the lowest value if all 3 tests are available (fish, daphniae, algae). These models have in common that they assume steady state concentrations in the aquatic environment. 

Zinc carbonate (0.6 to 5ppb seawater 5 to lOppb river water) has moderate solubility as a carbonate (21 mg/100 mL) (73). Zinc compounds are not particularly hazardous above certain limits they may be toxic and irritating. The maximum level allowed in sludge from wastewater is 3 g/kg. The predicted no effect concentration (PNEC) for ecotoxicological effects was 50 p g/L (5 pg/lOOmL) dissolved zinc (73). Current values are not a very serious risk. High zinc levels protect against cadmium intoxication and reduce lead absorption. Pockets of historical contamination exist (73). 

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