Hi Peder,

We met many years ago in Denmark and I have always been impressed with the quantity and quality of the work done by you and others on Indoor air in that relatively small country.   To try and answer your question, it may relate to California Proposition 65 and the cancer warning level associated with that statute.  I did the calculation many years ago (linearized model extrapolated down to 1 in 100,000 risk of cancer) and came up with 15 micrograms per person per day as the limits  for the threshold of warning that  "this product contains a product know to cause cancer."  I always considered this a bit of an overestimate for cancer and certainly well below any irritation limit.   

Hi Michael,

I do remember your visit many years ago and thanks for your response. I believe your calculation is debatable, because we now know (e.g. WHO (2010) 1) there is a definite no effect level for cancer of 0.1 mg/m3 (WHO, 2010) and 2) the concentration-response relationship is non-linear and biphasic?

As you can see from my question I am deeply confused about a number of observations in the paper by Bradman et al.

I wonder why Bradman et al. argue about health concerns in children referring to (McGwin et al., 2010). An inadequate study as discussed in detail by (Golden, 2011) and (Nielsen et al., 2013); furthermore, the NRC (US) concluded that the driving study ((Rumchev et al., 2002)) in the McGwin et al. analysis is unsupportable. In that respect, we also disregard the recent paper by (Kanchongkittiphon et al., 2015), because it violates basic Bradford Hill criteria of causation about formaldehyde and asthma and associated risk assessment.

 I wonder why Bradman et al. cite a number of papers ((Norbäck et al., 1995;Wieslander et al., 1997;Roda et al., 2011;Hulin et al., 2010)), although they have been shown to be inadequate for risk assessment of formaldehyde and asthma, as discussed in detail by (Golden, 2011), (Nielsen et al., 2013), and recently by (Nurmatov et al., 2015).

I wonder why Bradman et al. conclude that children should be more vulnerable than adults to formaldehyde exposure, well-knowing that the action of formaldehyde is located to the eyes and the nasal tissue causing sensory irritation in eyes and upper airways and nasal cancer. Furthermore, as discussed in (WHO, 2010;Wolkoff and Nielsen, 2010), no such support for differences has been found for formaldehyde; for further discussion, see also, e.g. (Ginsberg et al., 2010). Formaldehyde is deposited in the nasal cavity (85%) (Schroeter et al., 2014), thus discussion about dosage differences between adults and children becomes speculative, since dosimetric  CFD analysis indicated that adults are more exposed than children by induced DNA protein cross-linking; further, total extraction (adsorption rates per unit surface area of the nasal cavity) of formaldehyde appears to be similar in adults and children, see (Wolkoff and Nielsen, 2010). Furthermore, see also (Sweeney et al., 2015) about exposure differences of ethylbenzene regarding children vs adults. Thus, the assumption that children should be more vulnerable due to exposure differences appears not to be supported for formaldehyde.

I wonder why the OEHHA 8-hour and chronic guidelines are discussed, because they are based on an old Swedish study and the use of unjustified assessment factors, and this is unsuitable for risk assessment, as discussed in detail in WHO (2010) (Kaden et al), Wolkoff/Nielsen (2010), and Golden (2011). Further, I wonder why the French long-term guideline, which is based on the same Swedish study, is mentioned, although the inadequacy of that study for risk assessment has been clearly demonstrated in Nielsen et al (2013).

Perhaps, you are able to help me understanding this paper or provide me with papers that show my questions are unsupported?

Ginsberg G, Foos B, Dzubow R B and Firestone M (2010) Options for Incorporating Children's Inhaled Dose into Human Health Risk Assessment. Inhalation Toxicology 22:627-647.

Golden R (2011) Identifying an Indoor Air Exposure Limit for Formaldehyde Considering Both Irritation and Cancer Hazards. Critical Reviews in Toxicology 41:672-721.

Hulin M, Caillard D and Annesi-Maessano I (2010) Indoor Air Pollution and Childhood Asthma: Variation Between Urban and Rural Areas. Indoor Air 20:502-514.

Kanchongkittiphon W, Mendell M J, Gaffin J M, Wang G and Phipatanakul W (2015) Indoor Environmental Exposures and Exacerbation of Asthma: An Update to the 2000 Review by the Institute of Medicine. Environ Health Perspect 123:6-20.

McGwin JrG, Lienert J and Kennedy Jr J I (2010) Formaldehyde Exposure and Asthma in Children: A Systematic Review. Environ Health Perspect 118:313-317.

Nielsen GD, Larsen S T and Wolkoff P (2013) Recent Trend in Risk Assessment of Formaldehyde Exposures From Indoor Air. Arch Toxicol 87:73-98.

Norbäck D, Björnsson E, Janson C, Widström J and Boman G (1995) Asthmatic Symptoms and Volatile Organic Compounds, Formaldehyde, and Carbon Dioxide in Dwellings. Occup Environ Med 52:388-395.

Nurmatov UB, Tagiyeva N, Semple S, Devereux G and Sheikh A (2015) Volatile Organic Compounds and Risk of Asthma and Allergy: a Systematic Review. Eur Respir J 24:92-101.

Roda C, Kousignian I, Guihenneuc-Jouyaux C, Dassonville C, Nicolis I, Just J and Momas I (2011) Formaldehyde Exposure and Lower Respiratory Infections in Infants: Findings From the PARIS Cohort Study. Environ Health Perspect 119:1653-1658.

Rumchev K, Spickett J, Bulsara M, Philips M R and Stick S M (2002) Domestic Exposure of  to Formaldehyde Significantly Increases the Risk of Asthma in Young Children. Eur Respir J 20:403-406.

Schroeter JD, Campbell L, Kimbell J S, Conolly R B, Clewell III H J and Andersen M E (2014) Effects of Endogenous Formaldehyde in Nasal Tissues on Inhaled Formaldehyde Dosimetry Predictions in the Rat, Monkey, and Human Nasal Passage. Toxicol Sci 138:412-424.

Sweeney LM, Kester J E, Kirman C R, Gentry R P, Banton M I, Bus J S and Gargas M L (2015) Risk Assessment for Chronic Exposure of Children and Prospective Parents to Ethylbenzene (CAS No. 100-41-4). Crit Rev Toxicol 65:662-726.

Wieslander G, Norbäck D, Björnsson E, Janson C and Boman G (1997) Asthma and the Indoor Environment: the Significance of Emission of Formaldehyde and Volatile Organic Compounds From Newly Painted Indoor Surfaces. Int Arch Occup Environ Health 69:115-124.

Wolkoff P and Nielsen G D (2010) Non-Cancer Effects of Formaldehyde and Relevance for Setting an Indoor Air Guideline. Environ Int 36:788-799.

World Health Organization (2010) Selected Pollutants. WHO Indoor Air Quality Guidelines. WHO Regional Office for Europe, Copenhagen.

Hi Peder,

I believe you and I agree with you.  The calculation I was referring to was simply an application of the  linearized multistage model of cancer extrapolated to very low doses.  I believe that was clearly not  well developed science but governmental policy that lead California to use this method and to arrive at those very low numbers.  I agree that is is not a linear dose response and most likely a threshold effect.  I believe the low numbers are historical artifact at this point and in my opinion cannot stand the light of more recent and detailed scientific analysis.