Researchers at Washington State have put out an interesting study on dioxin exposure in rats. A good summary of that research is in this week’s online version of Scientific American, and the paper itself is available at PLOS One. In brief, the study showed that great-grandchildren of rats exposed to TCDD (think Agent Orange) exhibited a higher rate of disease than great-grandchildren of rats not exposed to TCDD. This is despite the great-grandchildren not being exposed to TCDD, supporting a conclusion that these third-generation rats inherited genetic damage from their great-grandparents, and that genetic damage was the cause of the increased disease rates.

The authors note that this study does not directly translate to humans because the exposure method of the study is different than the typical exposure scenario for humans. Nevertheless, I can’t help but speculate about potential regulatory implications of this emerging area of research.

For those of you that aren’t horribly familiar with human health risk assessments, various federal and state statutes set acceptable levels of cancer and non-cancer risk. This is usually done through the probability of cancer incidence for a specific lifetime of an individual in a specific population, based on a specific intake level of the substance in question. For instance, in Washington, contaminated sites are supposed to be remediated so that the remaining risk to humans posed by the site is generally attempted to be done to an excess cancer risk of one in one million (i.e., in a population of a million people, the site is expected to cause cancer in one individual). For fish consumption from such a site, the default fish “consumer” is assumed to weigh 70 kg, live for 75 years, and eat fish from the site for 30 years. The actual equation in Washington’s cleanup law looks like this:

[Equation 730-2]
Surface water cleanup level =(ug/l) RISK x ABW x AT x UCF1 x UCF2


CPF x BCF x FCR x FDF x ED

Where:
CPF = Carcinogenic potency factor as specified in WAC 173-340-708(8) (kg-day/mg)
RISK = Acceptable cancer risk level (1 in 1,000,000) (unitless)
ABW = Average body weight during the exposure duration (70 kg)
AT = Averaging time (75 years)
UCF1 = Unit conversion factor (1,000 ug/mg)
UCF2 = Unit conversion factor (1,000 grams/liter)
BCF = Bioconcentration factor as defined in WAC 173-340-708(9) (liters/kilogram)
FCR = Fish consumption rate (54 grams/day)
FDF = Fish diet fraction (0.5) (unitless)
ED = Exposure duration (30 years)

 

This emerging research into transgenerational effects has the potential to complicate these types of risk assessments. I won’t even attempt to try and rewrite the above equation, but think about having to propagate effects of toxic substances across generations–now you aren’t looking just at the typical 70 kg, 75 year-old person eating fish from a waterbody for 30 years, but that person’s children, grandchildren, great-grandchildren and beyond. Complicating things further is the real possibility that the transgenerational effects may not be the same as the effects seen in the exposed population. For instance, the authors of this current study of TCDD in rats note that the great-grandchildren had different types of diseases than their great-grandparents, and that exposure impacts even varied by sex.

Of course, it is important to reiterate that this current study isn’t directly applicable to humans for the reasons I discuss above, but as the Scientific American article notes, there are a wide variety of compounds that may have transgenerational effects in lab animals, including BPA, phthalates, some pesticides, and the insect repellent DEET. From a cleanup perspective, BPA and phthalates are two emerging classes of increasingly important drivers of cleanups, particularly of big, aquatic sites that receive large amounts of urban runoff. So, I can’t help but think this may be the leading edge of research that will eventually have dramatic regulatory impacts–although it may be 10 or 20 years of additional research that needs to be performed to see if these types of studies in rats do indeed indicate that similar impacts may be happening in humans.