Sunday, December 7, 2014

Chemical exposure risk assessment – what might we be missing?

Over the last few weeks this blog has featured a discussion of dermal exposure and how we might accomplish it.  That series was enhanced and prolonged from an email I received last month from Chris Packham. Chris sent me a copy of a talk he was going to give at a Regional BOHS Meeting in the UK on November 18, 2014.

I thought there was a lot of good information and perspective in that piece and Chris granted permission to put it here after his talk.   We may not agree specifically on the approach but I think everyone will agree that dermal exposure is a very important route in many exposure scenarios and has been somewhat ignored.

Chemical exposure risk assessment – 
what might we be missing?
Chris Packham

It is well established that inhalation of toxic chemicals can result in systemic effects, i.e. damage to internal organs and systems. A great deal of research and development has been undertaken resulting in strategies and equipment to monitor inhalation exposure. As a result in many countries there are exposure limits for a wide range of chemicals. Far less attention has been paid to the potential for chemicals to penetrate the skin and either cause or contribute to systemic toxic effects. Yet there is considerable evidence showing the potential for skin exposure to do this, including with chemicals that are unlikely ever to be inhaled because of their physical properties.(1) There is also a view that inhalation exposure results in more serious damage to health than can occur from skin exposure, often regarded as “just a rash”. Yet the EU Classification, Labelling and Packaging Regulation (EU1272/2008) contains the Hazard Statement 'H310 – Fatal in contact with skin'. 

In this article the authors will review the evidence showing why, in considering risks of damage to health due to the use of chemicals, the potential for skin exposure to cause systemic damage must be an integral part of any chemical exposure risk assessment. Firstly we need to recognise that the skin is not an impermeable barrier. The outermost layer, the stratum corneum, which forms 90% of the barrier, is, over most of our body, only as thick as the cling film that we use to wrap sandwiches. The way in which our skin interacts with the (working) environment is extremely complex and by no means scientifically fully understood. It is certainly beyond the scope of this article to attempt an in-depth explanation. (emphasis added)

Indeed, the complexity is such that the European Agency for Safety and Health at Work has stated: “However, there is no scientific method of measuring the results of the body’s exposure to risk through dermal contact. Consequently no dermal exposure standards have been set.” - from “Occupational skin diseases and dermal exposure in the European Union (EU-25):policy and practice overview - European Agency for Safety and Health at Work 

So where does this leave the health and safety practitioner attempting to establish the risks to the health of the workforce due to the presence of chemicals in their workplace? In the U.K. those chemicals that have been assigned a limit for airborne presence (Workplace Exposure Limit or WEL) and that are known to be able to penetrate the skin will be listed in the official hazard classification documentation(2) with an sk notation. However, this is far from a comprehensive list. Not only are there many chemicals that do not appear in this list that are able to penetrate the skin on their own and could then cause systemic damage. There are others that have systemic toxic properties but due to their form are on their own unlikely to be able to penetrate the skin. However, should these be mixed with a skin penetrant the potential for them then to able to cause systemic damage can be considerable. So establishing and assessing the hazard of a chemical in the workplace may not be as simple as many might assume. 

So what is the evidence that this is something that needs to be considered as significant when chemicals are being used in a workplace? The following statements and case studies should serve to illustrate why. 

1. Systemic uptake of 5-Hydroxy-N-methylpyrolidone

In this study(3) a comparison was made between the concentration of this chemical in urine arising from inhalation at 10mg/m3 over an 8 hour period with just 15 minutes exposure of one hand to a 15% solution in water. Despite the fact that skin exposure stopped after just 15 minutes, the concentration in urine continued to increase for several hours and matched that of the full 8 hour
respiratory exposure. The implications of this when conducting risk assessment are important as the assumption that the skin exposure is only for a very short period and therefore not of significance may not be correct. 

2. Systemic uptake of methylene diamine 

In a factory using this chemical in the manufacture of helicopter rotor blades this study (4) identified 14.7 μg/l of this chemical in urine under the actual working conditions initially observed. These did not include any effective control measures. By eliminating respiratory exposure the concentration was reduced to 12.1 μg/l. By allowing respiratory exposure but eliminating skin exposure the concentration was reduced to 2.6 μg/l. The conclusion that has to be drawn is that the major route of uptake was via the skin. 

3. Systemic effects in the rubber industry 

In his doctoral thesis (5) on genotoxic effects of dermal exposure in the rubber industry, Vermeulen comments: “Little attention has been paid to dermal exposure in this particular industry. Falck et al and Kilpikari already suggested in the early eighties that dermal absorption of chemical compounds could play an important part in the rubber industry. Direct evidence for this hypothesis was found in a study by Bros et al in an aircraft tire retreading company where a direct relation was found between dermal exposure to cyclohexane soluble matter and urinary mutagenicity while no relation was found between urinary mutagenicity and rubber particulates and fumes in air.” 

What should be clear from the above is that if we do not include the potential for skin uptake and the consequences we may well be missing a significant risk of serious damage to health. We need also to include the potential for ingestion as a route of uptake. 

The fact is that for systemic damage what is important is the total dose reaching the target organ, irrespective of the route of uptake. So what we need to identify is the combined uptake of all three routes: inhalation, dermal and ingestion. One of the immediate consequences of this is that with many chemicals the concept that ensuring airborne exposure is below the prescribed regulatory level represents adequate control may not be valid in terms of the true risk of damage to health. It may be necessary for regulatory compliance, but should the combination of the uptake of the three routes be sufficient to cause systemic damage, worker health can be severely, possibly permanently and potentially fatally, compromised. A consequence of this is that considering each of the three routes in isolation is no longer an acceptable approach. 

The problem now arises as to how we can develop a comprehensive risk assessment approach, combining the data on all three routes. Unfortunately very little seems to exist in terms of scientific studies or guidance on this. At the present time our only reliable technique appears to be that of biological monitoring of workers to establish their level of exposure, such as was carried out in the case study of exposure to methylene diamine described earlier in this article. Obviously it would be impracticable to do this for every chemical exposure risk assessment, but perhaps where there is evidence that the chemical which forms the subject of the risk assessment has properties that can cause systemic damage and that, under the particular circumstances prevailing in the work environment, there is potential for more than one form of exposure, biological monitoring should at least be considered. 

Ideally a database of results would be set up by a suitable organisation to build an evidence based overview of the true significance of this issue so that effective guidelines can be produced and perhaps new techniques developed. Until then the risk remains that we will continue to expose workers to situations that are putting their health in jeopardy.

(1) OSHA Technical Manual, Section II, Chapter 2 
(2) EH40/2005 Workplace exposure limits 
(3) Akrill et al (2002). Toxicol. Lett. 265 – 269 
(4) Weiss T, Schuster H, et al.; Dermal uptake and excretion of 4,4’-Methylenedianiline during rotor blade production in helicopter industry – an intervention study; Ann.Occup.Hyg, 2011, 55, 8, 886-892 
(5) Vermeulen R, genotoxic exposure and biological effects in the rubber manufacturing industry – relevance of the dermal route – doctoral thesis (2001)


  1. Hi Mike,
    Another clear example that showed that biological monitoring can clarify the significance of dermal uptake is from 2 decades ago. We did an intervention study with extra skin protective measures in a group of 13 coke oven workers. The study took place over 2 consecutive weeks. In week 1 the half of the group used regular respiratory protective equipment and regular dermal protective measures, the other half was following a program with extra protective measures to prevent/reduce skin exposure: daily a fresh laundered overall + underwear, every shift a new pair of gloves and following a washing procedure before each break (washing of both hands and face). In the second week the situation was crossed for both subgroups. 1-Hydroxypyrene in urine was measured as the biological indicator of PAH-exposure. The results were convincing: The average urinary levels of the 13 workers when involved in the hygienic program were significantly lower, on average 37%, the median levels being 1.3 instead of 2.3 micromole 1-hydroxypyrene per mole creatinine at the end of the workweek.
    Ref: VanRooij JG, Bodelier-Bade MM, Hopmans PM, Jongeneelen FJ. Reduction of urinary 1-hydroxypyrene excretion in coke-oven workers exposed to polycyclic aromatic hydrocarbons due to improved hygienic skin protective measures. Ann Occup Hyg. 1994 Jun;38(3):247-56.

  2. Frans,

    This is indeed compelling evidence. Many thanks for sharing it.


  3. This article is very informative and cool. Thanks for share this beautiful article.