Intestinal nutrient sensing: a gut feeling for food

Promotie

Dermal absorption and toxicological risk assessment:Pitfalls and promises

Promovendus mr. Drs HE (Harrie) Buist
Copromotor prof. dr RA Woutersen, dr JJM van de Sandt
Organisatie Wageningen University, Sub-department of Toxicology
Datum

vr 13 mei 2016 16:00 tot 17:30

Locatie Auditorium, building number 362
Generaal Foulkesweg 1
362
6703 BG Wageningen
0317-483592

Summary:

Absorption via the skin is an important phenomenon in the assessment of the risk of exposure to toxic substances. People are exposed to a variety of products via the skin. Pesticides, organic solvents and metalworking fluids are important in occupational skin exposure. In daily life, cosmetics, clothing and household products are the most relevant commodities with skin exposure. Hence, the objective of this thesis was to further develop, evaluate and improve methods for including skin absorption in the assessment of toxic risks.
People may be repeatedly exposed to products like disinfectants and cleaning liquids, which often contain aggressive substances that may damage the skin. The importance of this exposure was investigated for a selection of nine biocides. Single and repeated exposure to specific biocidal products (e.g. the quaternary ammonium chlorides) were proven to significantly increase skin permeability, especially when applied at high concentrations.

A computer model to predict skin absorption using simple experimental values and chemical properties as inputs, was developed. This model was baptized Dermal Absorption Model for Extrapolation (DAME) and provides a cost-effective means to estimate dermal absorption under different conditions.

Overall, it is concluded that dermal exposure can be an important factor in risks posed by chemicals and should be taken into account. The methods to do this are still open for further improvement, for instance via the development adequate combinations of simple absorption tests and computer models.

Propositions

  1. The permeation constant is a more versatile descriptor of dermal absorption than the relative absorbed dose.
    (this thesis)
  2. In vivo dermal absorption of a specific permeant can be predicted using a combination of in silico modelling and absorption parameters measured in vitro under infinite dose conditions.
    (this thesis)
  3. It is incorrect to subtract the carbon dioxide fixated in biodiesel from the carbon dioxide produced during combustion in order to establish the Global Warming Potential as done by (S&T)2 Consultants (2010), since this approach ignores carbon dioxide fixation by the vegetation or crops originally present on the land used for the biodiesel crop.
    (S&T)2 Consultants (2010). Lifecycle analysis Canola biodiesel. Prepared For: Canola Council of Canada. November 2010. (S&T)2 Consultants Inc., Delta, BC, Canada: page 31.
  4. As long as big data in toxicology refer to many parameter values on only a few substances, their potential to elucidate significant effects remains limited.
  5. As long as the investments far outweigh the returns, manned interplanetary space travel will remain a rich persons’ hobby.
  6. Money is a better incentive for change in behaviour than any campaign appealing to public moral or good sense.

Propositions pertaining to the thesis entitled:
“Dermal absorption and toxicological risk assessment: Pitfalls and promises”