You say that skin is a ‘robust barrier’. In some respects this is true, but it is also a barrier that is very thin. Over most of the body the stratum corneum is only 0.01mm thick and this is where we find the barrier. It is easily penetrated by many chemicals. A study by the Health and Safety Laboratory found that skin exposure of one hand to methyl-pyrrolidone as a 15% solution in water for just 15 minutes was equivalent to 8 hours inhalation exposure at 10 mg/m3. Another study in an aerospace plant found that skin was the major route of uptake for methylene dianiline (Weiss T, Schuster H, et al.; Dermal uptake and excretion of 4,4’-Methylenedianiline during rotor blade production in helicopter industry – and intervention study; Ann.Occup.Hyg, 2011, 55, 8, 886-892 ). There are also studies showing that skin exposure to isocyanates can initiate an allergy to isocyanates. (e.g. Redlich C,.A., Skin Exposure and Asthma – Is There a Connection, Proc Am Thorac Soc. Vol.7, 2010 )
Just a few additional examples:
“Skin absorption can occur without being noticed by the employee and in some instances may be a more significant route than the respiratory system. This is particularly true for non-volatile chemicals that are hazardous and that remain on work surfaces for long periods of time.” - OSHA Technical Manual, Section II, Chapter 2
“Direct transdermal uptake from air is not routinely considered. Yet the studies outlined in the previous paragraph suggest that, for at least some indoor pollutants, direct dermal uptake from air may occur at rates that are comporable to or larger than inhalation uptake.” – Weschler CJ, Nazarofi WW, Dermal Uptake of Organic Vapors Commonly Found in Indoor Air, Environmental Science & Technology, 2014, 48, 1230-1237
“Air threshold limits are insufficient to prevent adverse health effects in the case of contact with substances with a high dermal absorption potential.” - Drexler H, Skin protection and percutaneous absorption of chemical hazards, Int. Arch Occup. Environ. Health (2003) 76:359-361
“In many instances dermal exposure is the principal route of exposure, especially for chemicals which are relatively non-volatile. For example, biological monitoring results of coke oven workers coupled with air monitoring of the employees’ exposure demonstrated that 51% of the average total dose of benzo[a]pyrene adsorbed by coke oven workers occurred via skin contact. Studies of employees in the rubber industry suggest that exposure to genotoxic chemicals present in the workplace is greater via the skin than via the lung.” - OSHA Technical Manual, Section II, Chapter 2
So concentration on inhalation exposure may not be sufficient. We need to keep in mind that it is the total dose reaching an organ that is important, irrespective of the route(s) of uptake.
Chris