The American Society for Testing and Materials (ASTM) mouse bioassay, which quantifies airway irritation from reduction in the respiratory rate, was used to find evidence for the formation of highly irritating substances in reactions of ozone with terpenes (common indoor volatile organic compounds (VOCs)). No-observed-effect-levels (NOELs) and concentration-effect relationships were established for ozone, (+)-alpha-pinene and R-(+)-limonene, isoprene, and some of their major reaction products. Reaction mixtures of excess terpene and ozone considerably below their NOEL concentrations resulted in significant upper airway irritation. The reduction of the respiratory rate was from 30% to about 50%, lowest for the alpha-pinene and highest for the isoprene mixture. Chemical analysis of reaction mixtures by conventional methods showed that readily identified stable products and residual reactants at the concentrations found could not account for the observed reductions of the respiratory rate, assuming additivity of the reaction products. The results suggest that, in addition to known irritants (formaldehyde, acrolein, methacrolein, methyl vinylketone), one or more strong airway irritant(s) of unknown structure(s) were formed. Future indoor air quality (IAQ) guidelines for unsaturated VOCs (e.g., terpenes) and their emission from building products may require the consideration of reactions with oxidants, like ozone. Similarly, effects of ozone-emitting equipment should be re-evaluated.

Fullerenes represent a group of nanoparticles discovered in 1985. They are spherical molecules consisting entirely of carbon atoms (C x ) to which side chains can be added, furnishing compounds with widely different properties. Fullerenes interact with biological systems, for example, by enzyme inhibition, causing phototoxic reactions, being scavengers of reactive oxygen species and free radicals, in addition to being able to initiate free radical reactions. Absorption, distribution and excretion strongly depend on the properties of the side chains. The pristine C 60 has a very long biological half-life, whereas the most water-soluble derivatives are eliminated from the exposed animals within weeks. A long biological half-life raises concern about bioaccumulation and long-term effects. In general, the acute oral, dermal and airway toxicity is low. However, few relevant experimental studies of repeated dose toxicity, reproductive toxicity and carcinogenic effect are available. The data suggest that direct DNA damaging effects are low, but formation of reactive oxygen species may cause inflammation and genetic damage. Apparently, it is dose-dependent whether a beneficial or an adverse effect occurs.Nanoparticle-based technology is a rapidly growing area of interest [1,2], which takes advantage of the fact that the specific surface area increases dramatically at small-size particles, thus these particles may have properties that are different from corresponding particles with larger size [1][2][3]. This also applies for toxicity, which, among other factors, depends on surface area, chemical composition and shape [3]. Nanoparticles (<100 nm, at least in one dimension) comprise naturally occurring (e.g. combustion products) and engineered/ manufactured nanoparticles [3]. Nanoparticles are used, for example, in electronic equipments [1,2] In a recent publication from the German chemical industry, it appeared that the most commonly used manufactured nanoparticles are sialic acid, metal nanoparticles, metal oxides, silicate, carbon black, nanosilver, pharmaceutical products and other nanoparticles [7]. The similar bulk materials were used in the UK in addition to niche products such as fullerenes, carbon nanotubes, nanowires, quantum dots and other nanoparticles [2]. A large-scale production plant for fullerene has recently been opened in Japan, allowing a production of a high tonnage per year [2]. Due to the high electron affinity and superior ability to transport charge, fullerene-based solar cells are currently accepted as being the most effective for this purpose [8]. The in vivo biology and toxicology of fullerenes are the subjects of this MiniReview not only as fullerenes are interesting due to their technical properties, but also as they are considered candidates for new drugs, new antioxidants and new radicalscavenging compounds [5,9,10]. Further examples of in vitro effects are available from the recent review [10]. In vitro toxicity is only considered where assumed to contribute to the understanding ...

Formaldehyde is a ubiquitous indoor air pollutant that is classified as “Carcinogenic to humans (Group 1)” (IARC, Formaldehyde, 2-butoxyethanol and 1-tert-butoxypropanol-2-ol. IARC monographs on the evaluation of carcinogenic risks to humans, vol 88. World Health Organization, Lyon, pp 39–325, 2006). For nasal cancer in rats, the exposure–response relationship is highly non-linear, supporting a no-observed-adverse-effect level (NOAEL) that allows setting a guideline value. Epidemiological studies reported no increased incidence of nasopharyngeal cancer in humans below a mean level of 1 ppm and peak levels below 4 ppm, consistent with results from rat studies. Rat studies indicate that cytotoxicity-induced cell proliferation (NOAEL at 1 ppm) is a key mechanism in development of nasal cancer. However, the linear unit risk approach that is based on conservative (“worst-case”) considerations is also used for risk characterization of formaldehyde exposures. Lymphohematopoietic malignancies are not observed consistently in animal studies and if caused by formaldehyde in humans, they are high-dose phenomenons with non-linear exposure–response relationships. Apparently, these diseases are not reported in epidemiological studies at peak exposures below 2 ppm and average exposures below 0.5 ppm. At the similar airborne exposure levels in rodents, the nasal cancer effect is much more prominent than lymphohematopoietic malignancies. Thus, prevention of nasal cancer is considered to prevent lymphohematopoietic malignancies. Departing from the rat studies, the guideline value of the WHO (Air quality guidelines for Europe, 2nd edn. World Health Organization, Regional Office for Europe, Copenhagen, pp 87–91, 2000), 0.08 ppm (0.1 mg m−3) formaldehyde, is considered preventive of carcinogenic effects in compliance with epidemiological findings.

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In 2010, the World Health Organization (WHO) established an indoor air quality guideline for short- and long-term exposures to formaldehyde (FA) of 0.1 mg/m3 (0.08 ppm) for all 30-min periods at lifelong exposure. This guideline was supported by studies from 2010 to 2013. Since 2013, new key studies have been published and key cancer cohorts have been updated, which we have evaluated and compared with the WHO guideline. FA is genotoxic, causing DNA adduct formation, and has a clastogenic effect; exposure–response relationships were nonlinear. Relevant genetic polymorphisms were not identified. Normal indoor air FA concentrations do not pass beyond the respiratory epithelium, and therefore FA’s direct effects are limited to portal-of-entry effects. However, systemic effects have been observed in rats and mice, which may be due to secondary effects as airway inflammation and (sensory) irritation of eyes and the upper airways, which inter alia decreases respiratory ventilation. Both secondary effects are prevented at the guideline level. Nasopharyngeal cancer and leukaemia were observed inconsistently among studies; new updates of the US National Cancer Institute (NCI) cohort confirmed that the relative risk was not increased with mean FA exposures below 1 ppm and peak exposures below 4 ppm. Hodgkin’s lymphoma, not observed in the other studies reviewed and not considered FA dependent, was increased in the NCI cohort at a mean concentration ≥0.6 mg/m3 and at peak exposures ≥2.5 mg/m3; both levels are above the WHO guideline. Overall, the credibility of the WHO guideline has not been challenged by new studies.