Chapter 8
Mixtures
A recent study (Pelletier et al. (2018) Environment International 117, 22–32) has dealt with the cumulative risk assessment of residential indoor exposure to semi-volatile organic compounds in France. The table lists the aggregate daily doses and the derived no effect levels. Are any of these chemicals posing a risk to human health? What about the mixture? What is the risk index? What is the maximum cumulative ratio?
| Chemical in the indoor environment |
Aggregated daily doses (ng/kgbw/d) |
Derived no effect level (ng/kgbw/d) |
|---|---|---|
| Aldrin | 0.3 | 30 |
| Lindane | 1 | 100 |
| Chlorpyrifos | 0.1 | 100 |
| Tributylphosphate | 1 | 10000 |
| Galaxolide | 150 | 150000 |
| Benzo[a]pyrene | 0.1 | 100 |
| DEHP | 1000 | 5000 |
| BDE 47 | 4 | 2 |
Note: The numbers have been adapted from the original paper to simplify the problem.
The German Environmental Protection Agency UBA performed a retrospective human health risk assessment for five phthalates (DBP,di-n-butyl phthalate; DIBP, di-iso-butyl phthalate; BBP, butylbenzyl phthalate; DEHP, di(2-ethylhexyl) phthalate; DINP, di-iso-nonyl phthalate) over 27 years. They all act as antiandrogens, adversely affecting male fertility. The Derived No Effect Level (DNEL) were derived for a similar effect, the suppression of foetal testicular testosterone synthesis, an effect that is common for many phthalates.
| Phthalate |
Derived no effect level (µg/kgbw/d) |
1988 Daily intake (µg/kgbw/d) |
2015 Daily intake (µg/kgbw/d) |
|---|---|---|---|
| DBP | 10 | 20 | 0.5 |
| DIBP | 100 | 0.25 | 0.05 |
| BBP | 10 | 1 | 0.5 |
| DEHP | 10 | 5 | 0.5 |
| DINP | 50 | 0.25 | 0.5 |
The total amount of these five phthalates was reduced 13-fold in the 27 years from 1988 to 2015 and the mixture risk index also decreased by a factor of 16. Which phthalate(s) was(were) the risk driver(s) in 1988 and which one(s) in 2015? What changed with respect of the relevance of mixtures?
(Note: The data are modified from Apel et al. 2020, 10.1016/j.envint.2020.105467 for easier calculation)
In complex environmental samples, hundreds and thousands of chemicals might act together in mixtures. We typically invoke the mixture concept of concentration addition to predict the mixture effects of the detected chemicals. The detected chemicals often explain only a small fraction of the measured biological effects of the same sample. The simplest explanation is that there are bioactive chemicals that are not captured by chemical analysis. Which other reasons might be conceivable? Is there a difference on that matter between reporter gene assays and apical endpoints such as cytotoxicity or survival?