Toxicological Evaluation and Limit Values for 2-Ethylhexyl acrylate, Propylene carbonate, Quaternary ammonium compounds, Triglycidyl isocyanurate, and Tripropyleneglycol diacrylate

Principles for setting of health based limit values for chemical substances

In the following, the principles upon which the Danish Environmental Protection Agency bases the health based limit values, in the following referred to as limit values, for chemical substances are briefly outlined. For further and more specific information, the reader is referred to the references mentioned below.

Purpose

The purpose of setting limit values for chemical substances is to prevent health hazards in the human population caused by chemicals as pollutants. The scientific method for setting of limit values comprises a hazard identification and hazard assessment which together with an exposure assessment constitute the risk assessment part in the proces of setting limit values.

Selection of data

Data concerning exposure and harmful effects of a chemical substance are collected from national and international criteria documents, monographs and original scientific literature. During the review of the data, the quality and reliability of the studies and research work are critically assessed. This is an important step since conflicting viewpoints regarding the hazards may be present. Unpublished data from industry or other sources are only seldom used, as such data have not been published in scientific journals and have not been subjected to critical review by other scientists.

If adequate human data are available these are preferred as the basis for the assessment. For most substances however, human data are not adequate or available. In these cases, limit values are based upon data from experimental animal studies.

When all the relevant data have been evaluated, the hazard considered most important - "the critical effect" - for setting the limit value, is identified. In this step it is assessed whether an effect should be considered as adverse and of relevance to humans.

A substance may have different effects at different concentrations or doses. Generally, the effects are of more concern the lower the concentration or dose at which they occur, and the effect observed at the lowest concentration or dose often forms the basis for setting the limit value.

Threshold chemicals, NOAEL or LOAEL

The next step for assessment of a limit value is to identify the "no observed adverse effect level" (NOAEL) which is the highest dose at which the critical effect was not observed or, in cases where a NOAEL cannot be identified, the "lowest observed adverse effect level" (LOAEL) which is the lowest dose at which the critical effect was observed.

TDI / safety factors

Having identified a NOAEL or a LOAEL, three "safety factors" (SF) are used to extrapolate from NOAEL or LOAEL to the tolerable daily intake, TDI (expressed in mg/kg b.w. per day) or the limit value for air, LV_air, (expressed in mg/m³). The purpose of the safety factors is to take into account the fact that:

Thus in cases where a threshold value for the toxic effect is assumed and a NOAEL or a LOAEL can be identified, the TDI or the LV_air are obtained by the following calculation:

Exposure routes

In general, limit values for air are based upon data from inhalation studies and limit values for soil (LV_soil) and drinking water (LV_dw) are based upon data from oral studies. However, if data for the relevant exposure route are not available, data from alternative exposure routes may be used as well, although it is realized that the degree of uncertainty may increase. This will then influence the value of the SF₃.

Analogy

In cases where no data on harmful effects are available, an evaluation may be made upon the basis of data for related substances and a consequent increase in the value of the SF₃.

Non threshold chemicals

For chemical substances where a threshold value for the toxic effect cannot be assumed (i.e. genotoxic carcinogenic substances), the concept of lifetime risk is applied. Thus, for these potential carcinogenic substances, the TDI corresponding to a specific lifetime risk, is calculated upon the basis of animal studies by means of the "One Hit" model. A lifetime risk of 10^-6 (life-time exposure to the dose that may lead to cancer for one in a million) is considered as tolerable.

Having obtained the tolerable daily intake for a chemical substance, the limit values for drinking water and soil are calculated taking into account the daily exposure from the various media. The following exposure standard estimates for the various media are used in the calculation of limit values:

*For the soil exposure estimates, it has to be emphasized that these are based upon exposure scenarios which cover the most sensitive applications, e.g. domestic gardens, play grounds or kindergartens.

To ensure that the total daily intake of a chemical substance from the various media does not exceed the tolerable daily intake, a certain percentage of the tolerable intake to the various media may be assigned (allocation).

Limit values

The limit value for soil and drinking water are obtained by the following calculations:

*TDI or a percentage of the TDI (allocation)
w: body weight for a child (10 kg) or an adult person (70 kg)

C-value, quality criteria

Finally, the limit values are used as the basis for the setting of quality criteria for soil, drinking water, and air (C-values). In this step, other than health based viewpoints may be taken into account. This may include aesthetical factors such as odour (all media), discoloration (soil, drinking water), taste and microbial growth (drinking water). Furthermore, economic or political administrative factors may be taken into account.

It has to be stressed that no ecotoxicological considerations are taken into account in the process of setting health based limit values.

References

Industrial Air Pollution Control Guidelines. Vejledning fra Miljøstyrelsen Nr. 9 1992. Ministry of the Environment, Denmark, Danish Environmental Protection Agency.

Health Based Evaluations of Chemical Substances in Drinking Water. Vejledning fra Miljøstyrelsen Nr. 1 1992. Ministry of the Environment, Denmark, Danish Environmental Protection Agency. In Danish.

Risk Evaluation of Contaminated Sites. Miljøprojekt Nr. 123 1990. Ministry of the Environment, Denmark, Danish Environmental Protection Agency. In Danish.