Squalene Depletion in Skin Following Human Exposure to Ozone under Controlled Chamber Conditions.

A major component of human skin oil is squalene, a highly unsaturated hydrocarbon that protects the skin from atmospheric oxidants. Skin oil, and thus squalene, is continuously replenished on the skin surface. Squalene is also quickly consumed through reactions with ozone and other oxidants. This study examined the extent of squalene depletion in the skin oils of the forearm of human volunteers after exposure to ozone in a climate chamber. Temperature, relative humidity (RH), skin coverage by clothing, and participants' age were varied in a controlled manner. Concentrations of squalene were determined in skin wipe samples collected before and after ozone exposure. Exposures to ozone resulted in statistically significant decreases in post-exposure squalene concentrations compared to pre-exposure squalene concentrations in the skin wipes when squalene concentrations were normalized by concentrations of co-occurring cholesterol but not by co-occurring pyroglutamic acid (PGA). The rate of squalene loss due to ozonolysis was lower than its replenishment on the skin surface. Within the ranges examined, temperature and RH did not significantly affect the difference between normalized squalene levels in post-samples versus pre-samples. Although not statistically significant, skin coverage and age of the volunteers (three young adults, three seniors, and three teenagers) did appear to impact squalene depletion on the skin surfaces.

Food contact materials: an effect-based evaluation of the presence of hazardous chemicals in paper and cardboard packaging.

Food contact materials (FCMs) can contain hazardous chemicals that may have the potential to migrate into food and pose a health hazard for humans. Previous studies have mainly focused on plastic materials, while data on packaging materials made from paper and cardboard are limited. We used a panel of cell-based bioassays to investigate the presence and impact of bioactive chemicals on human relevant endpoints like oxidative stress, genotoxicity, inflammation, xenobiotic metabolism and endocrine system effects in extracts made from paper and cardboard. In total, 23 methanol extracts of commonly used paper and cardboard available on the Swedish market were extracted as a whole product using methanol to retrieve polar substances, and tested at concentrations 0.3-10 mg/mL and 0.2-6 mg/mL. At the highest concentration bioactivities were observed in a high proportion of the samples: oxidative stress (52%), genotoxicity (100%), xenobiotic metabolism (74%), antiandrogenic- (52%) and antioestrogenic receptor (39%). Packages of potential concern included cake/pastry boxes/mats, boxes for infant formula/skimmed milk, pizza boxes, pizza slice trays and bag of cookies. It should be noted that the extraction for packages like cake/pastry boxes can be considered exaggerated, as the exposure usually is shorter. It can be hypothesised that the observed responses may be explained by inks, coatings, contaminants and/or naturally occurring compounds within the material. To summarise, an effect-based approach enables hazard identification of chemicals within FCMs, which is a valuable tool for ensuring safe use of FCMs.

The effect of reduction measures on concentrations of hazardous semivolatile organic compounds in indoor air and dust of Swedish preschools.

Young children spend a substantial part of their waking time in preschools. It is therefore important to reduce the load of hazardous semivolatile organic compounds (SVOCs) in the preschools' indoor environment. The presence and levels of five SVOC groups were evaluated (1) in a newly built preschool, (2) before and after renovation of a preschool, and (3) in a preschool where SVOC-containing articles were removed. The new building and the renovation were performed using construction materials that were approved with respect to content of restricted chemicals. SVOC substance groups were measured in indoor air and settled dust and included phthalates and alternative plasticizers, organophosphate esters (OPEs), brominated flame retardants, and bisphenols. The most abundant substance groups in both indoor air and dust were phthalates and alternative plasticizers and OPEs. SVOC concentrations were lower or of the same order of magnitude as those reported in comparable studies. The relative Cumulative Hazard Quotient (HQcum ) was used to assess the effects of the different reduction measures on children's SVOC exposure from indoor air and dust in the preschools. HQcum values were low (1.0-6.1%) in all three preschools and decreased further after renovation and article substitution. The SVOCs concentrations decreased significantly more in the preschool renovated with the approved building materials than in the preschool where the SVOC-containing articles were removed.

Reduction of hazardous chemicals in Swedish preschool dust through article substitution actions.

Consumer goods and building materials present in the preschool environment can be important sources of hazardous chemicals, such as plasticizers, bisphenols, organophosphorus and brominated flame retardants, poly- and perfluoroalkyl substances, which may pose a health risk to children. Even though exposure occurs via many different pathways, such as food intake, inhalation, dermal exposure, mouthing of toys etc., dust has been identified as a valuable indicator for indoor exposure. In the present study, we evaluate the efficiency of product substitution actions taken in 20 Swedish preschools from the Stockholm area to reduce the presence of hazardous substances in indoor environments. Dust samples were collected from elevated surfaces in rooms where children have their everyday activities, and the concentrations found were compared to the levels from a previous study conducted in 2015 at the same preschools. It was possible to lower levels of hazardous substances in dust, but their continued presence in the everyday environment of children was confirmed since bisphenol A, restricted phthalates and organophosphate esters were still detectable in all preschools. Also, an increase in the levels of some of the substitutes for the nowadays restricted substances was noted; some of the alternative plasticizers to phthalates, such as DEHA and DEHT, were found with increased concentrations. DINP was the dominant plasticizer in preschool dust with a median concentration of 389 µg/g, while its level was significantly (p = 0.012) higher at 716 µg/g in preschools with polyvinyl chloride (PVC) flooring. PBDEs were now less frequently detected in dust and their levels decreased 20% to 30%. This was one of the few times that PFAS were analyzed in preschool dust, where 6:2 diPAP was found to be most abundant with a median concentration of 1140 ng/g, followed by 6:2 PAP 151 ng/g, 8:2 diPAP 36 ng/g, N-Et-FOSAA 18 ng/g, PFOS 12 ng/g, PFOA 7.7 ng/g and PFNA 1.1 ng/g. In addition, fluorotelomer alcohols were detected in 65-90% of the samples. Children's exposure via dust ingestion was evaluated using intermediate and high daily intake rates of the targeted chemicals and established health limit values. In each case, the hazard quotients (HQs) were < 1, and the risk for children to have adverse health effects from the hazardous chemicals analyzed in this study via dust ingestion was even lower after the product substitution actions were taken in preschools.

Hand Wipes: A Useful Tool for Assessing Human Exposure to Poly- and Perfluoroalkyl Substances (PFASs) through Hand-to-Mouth and Dermal Contacts.

The indoor environment contributes considerably to human exposure to poly- and perfluoroalkyl substances (PFASs). This study estimated the human exposure to PFASs from the indoor environment through hand-to-mouth and dermal contacts using hand wipes. An analytical method was developed to determine 25 PFASs in hand wipe samples collected as a composite sample from both hands of 60 adults. Polyfluoroalkyl phosphate esters (PAPs) were the predominant PFASs in the hand wipe samples (medians between 0.21 and 0.54 ng per sample). Positive and significant correlations were observed between PAPs, perfluorooctanesulfonate (PFOS), and perfluorooctanoate (PFOA) in hand wipes. Low frequency of daily hand washing (≤8 times day-1) was associated with 30-50% higher concentrations of PFOS, PFOA, and 8:2diPAP in hand wipes. Further, significant correlations between paired hand wipes and house dust samples were observed for PFOS, PFOA, and 6:2diPAP. Also, a significant correlation between PFOS in hand wipes and EtFOSE in indoor air was found. This finding indicates either a common source of exposure or a transformation of EtFOSE to PFOS in the environment or on the hands. The contributions of direct and indirect exposure to perfluoroalkyl acids (PFAAs) showed that PFOA contributed the highest exposure to adults via hand-to-mouth and dermal contacts, followed by PFOS. The median of estimated daily intakes via hand-to-mouth and dermal contacts (for hands only) for PFOA were 0.83 and 0.50 pg·kg bw-1·day-1, respectively. This study gives a first indication that PFAS concentrations in hand wipes can be used as a proxy for the exposure to PFASs from indoor environments, but further studies are needed to confirm this.

Perfluoroalkyl acids and their precursors in floor dust of children's bedrooms - Implications for indoor exposure.

We analysed floor dust samples from 65 children's bedrooms in Finland collected in 2014/2015 for 62 different per- and polyfluoroalkyl substances (PFASs) with a simple and highly efficient method. Validation results from the analysis of standard reference material (SRM) 2585 were in good agreement with literature data, while 24 PFASs were quantified for the first time. In the dust samples from children's bedrooms, five perfluoroalkyl carboxylic acids (PFCAs) and perfluorooctane sulfonic acid (PFOS) were detected in more than half of the samples with the highest median concentration of 5.26 ng/g for perfluorooctanoic acid (PFOA). However, the dust samples were dominated by polyfluoroalkyl phosphoric acid esters (PAPs) and fluorotelomer alcohols (FTOHs) (highest medians: 53.9 ng/g for 6:2 diPAP and 45.7 ng/g for 8:2 FTOH). Several significant and strong correlations (up to ρ = 0.95) were found among different PFASs in dust as well as between PFASs in dust and air samples (previously published) from the same rooms. The logarithm of dust to air concentrations (log Kdust/air) plotted against the logarithm of the octanol-air partition coefficient (log Koa) resulted in a significant linear regression line with R2 > 0.88. Higher dust levels of PFOS were detected in rooms with plastic flooring material in comparison to wood (p < 0.05). Total estimated daily intakes via dust (EDIdust) and air (EDIair) of perfluoroalkyl acids (PFAA), including biotransformation of precursors to PFAAs, were calculated for 10.5-year-old children. The total EDIdust for PFOA and PFOS were estimated to be 0.007 ng/kg bw/day and 0.006 ng/kg bw/day, respectively, in an intermediate exposure scenario. The sum of the total EDIs for all PFAAs was slightly higher for dust than air (0.027 and 0.019 ng/kg bw/day). Precursor biotransformation was generally important for total PFOS intake, while for the PFCAs, FTOH biotransformation was estimated to be important for air, but not for dust exposure.

Multi-pathway human exposure assessment of phthalate esters and DINCH.

Phthalate esters are substances mainly used as plasticizers in various applications. Some have been restricted and phased out due to their adverse health effects and ubiquitous presence, leading to the introduction of alternative plasticizers, such as DINCH. Using a comprehensive dataset from a Norwegian study population, human exposure to DMP, DEP, DnBP, DiBP, BBzP, DEHP, DINP, DIDP, DPHP and DINCH was assessed by measuring their presence in external exposure media, allowing an estimation of the total intake, as well as the relative importance of different uptake pathways. Intake via different uptake routes, in particular inhalation, dermal absorption, and oral uptake was estimated and total intake based on all uptake pathways was compared to the calculated intake from biomonitoring data. Hand wipe results were used to determine dermal uptake and compared to other exposure sources such as air, dust and personal care products. Results showed that the calculated total intakes were similar, but slightly higher than those based on biomonitoring methods by 1.1 to 3 times (median), indicating a good understanding of important uptake pathways. The relative importance of different uptake pathways was comparable to other studies, where inhalation was important for lower molecular weight phthalates, and negligible for the higher molecular weight phthalates and DINCH. Dietary intake was the predominant exposure route for all analyzed substances. Dermal uptake based on hand wipes was much lower (median up to 2000 times) than the total dermal uptake via air, dust and personal care products. Still, dermal uptake is not a well-studied exposure pathway and several research gaps (e.g. absorption fractions) remain. Based on calculated intakes, the exposure for the Norwegian participants to the phthalates and DINCH was lower than health based limit values. Nevertheless, exposure to alternative plasticizers, such as DPHP and DINCH, is expected to increase in the future and continuous monitoring is required.

Phthalates, non-phthalate plasticizers and bisphenols in Swedish preschool dust in relation to children's exposure.

Children are exposed to a wide range of chemicals in their everyday environments, including the preschool. In this study, we evaluated the levels of phthalates, non-phthalate plasticizers and bisphenols in dust from 100 Swedish preschools and identified important exposure factors in the indoor environment. In addition, children's total exposure to these chemicals was determined by urine analysis to investigate their relation with dust exposure, and to explore the time trends by comparing with children who provided urine fifteen years earlier. The most abundant plasticizers in preschool dust were the phthalates di-isononyl phthalate (DiNP) and di-(2-ethylhexyl) phthalate (DEHP) with geometric mean levels of 450 and 266µg/g dust, respectively, and the non-phthalate plasticizers bis(2-ethylhexyl) terephthalate (DEHT) and diisononylcyclohexane-1,2-dicarboxylate (DiNCH) found at 105 and 73µg/g dust, respectively. The levels of several substitute plasticizers were higher in newer preschools, whereas the levels of the strictly regulated phthalate di-n-butyl phthalate (DnBP) were higher in older preschools. The presence of foam mattresses and PVC flooring in the sampling room were associated with higher levels of DiNP in dust. Children's exposure from preschool dust ingestion was below established health based reference values and the estimated exposure to different phthalates and BPA via preschool dust ingestion accounted for 2-27% of the total exposure. We found significantly lower urinary levels of BPA and metabolites of strictly regulated phthalates, but higher levels of DiNP metabolites, in urine from the children in this study compared to the children who provided urine samples fifteen years earlier.

Case Study on Screening Emerging Pollutants in Urine and Nails.

Alternative plasticizers and flame retardants (FRs) have been introduced as replacements for banned or restricted chemicals, but much is still unknown about their metabolism and occurrence in humans. We identified the metabolites formed in vitro for four alternative plasticizers (acetyltributyl citrate (ATBC), bis(2-propylheptyl) phthalate (DPHP), bis(2-ethylhexyl) terephthalate (DEHTP), bis(2-ethylhexyl) adipate (DEHA)), and one FR (2,2-bis (chloromethyl)-propane-1,3-diyltetrakis(2-chloroethyl) bisphosphate (V6)). Further, these compounds and their metabolites were investigated by LC/ESI-Orbitrap-MS in urine and finger nails collected from a Norwegian cohort. Primary and secondary ATBC metabolites had detection frequencies (% DF) in finger nails ranging from 46 to 95%. V6 was identified for the first time in finger nails, suggesting that this matrix may also indicate past exposure to FRs as well as alternative plasticizers. Two isomeric forms of DEHTP primary metabolite were highly detected in urine (97% DF) and identified in finger nails, while no DPHP metabolites were detected in vivo. Primary and secondary DEHA metabolites were identified in both matrices, and the relative proportion of the secondary metabolites was higher in urine than in finger nails; the opposite was observed for the primary metabolites. As many of the metabolites present in in vitro extracts were further identified in vivo in urine and finger nail samples, this suggests that in vitro assays can reliably mimic the in vivo processes. Finger nails may be a useful noninvasive matrix for human biomonitoring of specific organic contaminants, but further validation is needed.

Evaluation of exposure to phthalate esters and DINCH in urine and nails from a Norwegian study population.

Phthalate esters (PEs) and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) used as additives in numerous consumer products are continuously released into the environment, leading to subsequent human exposure which might cause adverse health effects. The human biomonitoring approach allows the detection of PEs and DINCH in specific populations, by taking into account all possible routes of exposure (e.g. inhalation, transdermal and oral) and all relevant sources (e.g. air, dust, personal care products, diet). We have investigated the presence of nine PE and two DINCH metabolites and their exposure determinants in 61 adult residents of the Oslo area (Norway). Three urine spots and fingernails were collected from each participant according to established sampling protocols. Metabolite analysis was performed by LC-MS/MS. Metabolite levels in urine were used to back-calculate the total exposure to their corresponding parent compound. The primary monoesters, such as monomethyl phthalate (MMP, geometric mean 89.7ng/g), monoethyl phthalate (MEP, 104.8ng/g) and mono-n-butyl phthalate (MnBP, 89.3ng/g) were observed in higher levels in nails, whereas the secondary bis(2-ethylhexyl) phthalate (DEHP) and DINCH oxidative metabolites were more abundant in urine (detection frequency 84-100%). The estimated daily intakes of PEs and DINCH for this Norwegian population did not exceed the established tolerable daily intake and reference doses, and the cumulative risk assessment for combined exposure to plasticizers with similar toxic endpoints indicated no health concerns for the selected population. We found a moderate positive correlation between MEP levels in 3 urine spots and nails (range: 0.56-0.68). Higher frequency of personal care products use was associated with greater MEP concentrations in both urine and nail samples. Increased age, smoking, wearing plastic gloves during house cleaning, consuming food with plastic packaging and eating with hands were associated with higher levels in urine and nails for some of the metabolites. In contrast, frequent hair and hand washing was associated with lower urinary levels of monoisobutyl phthalate (MiBP) and mono(2-ethyl-5-hydroxyhexyl) phthalate (5-OH-MEHP), respectively.

Comprehensive Study of Human External Exposure to Organophosphate Flame Retardants via Air, Dust, and Hand Wipes: The Importance of Sampling and Assessment Strategy.

We compared the human exposure to organophosphate flame retardants (PFRs) via inhalation, dust ingestion, and dermal absorption using different sampling and assessment strategies. Air (indoor stationary air and personal ambient air), dust (floor dust and surface dust), and hand wipes were sampled from 61 participants and their houses. We found that stationary air contains higher levels of ΣPFRs (median = 163 ng/m(3), IQR = 161 ng/m(3)) than personal air (median = 44 ng/m(3), IQR = 55 ng/m(3)), suggesting that the stationary air sample could generate a larger bias for inhalation exposure assessment. Tris(chloropropyl) phosphate isomers (ΣTCPP) accounted for over 80% of ΣPFRs in both stationary and personal air. PFRs were frequently detected in both surface dust (ΣPFRs median = 33 100 ng/g, IQR = 62 300 ng/g) and floor dust (ΣPFRs median = 20 500 ng/g, IQR = 30 300 ng/g). Tris(2-butoxylethyl) phosphate (TBOEP) accounted for 40% and 60% of ΣPFRs in surface and floor dust, respectively, followed by ΣTCPP (30% and 20%, respectively). TBOEP (median = 46 ng, IQR = 69 ng) and ΣTCPP (median = 37 ng, IQR = 49 ng) were also frequently detected in hand wipe samples. For the first time, a comprehensive assessment of human exposure to PFRs via inhalation, dust ingestion, and dermal absorption was conducted with individual personal data rather than reference factors of the general population. Inhalation seems to be the major exposure pathway for ΣTCPP and tris(2-chloroethyl) phosphate (TCEP), while participants had higher exposure to TBOEP and triphenyl phosphate (TPHP) via dust ingestion. Estimated exposure to ΣPFRs was the highest with stationary air inhalation (median =34 ng·kg bw(-1)·day(-1), IQR = 38 ng·kg bw(-1)·day(-1)), followed by surface dust ingestion (median = 13 ng·kg bw(-1)·day(-1), IQR = 28 ng·kg bw(-1)·day(-1)), floor dust ingestion and personal air inhalation. The median dermal exposure on hand wipes was 0.32 ng·kg bw(-1)·day(-1) (IQR = 0.58 ng·kg bw(-1)·day(-1)) for ΣTCPP. The selection of sampling and assessment strategies could significantly affect the results of exposure assessment.

Human exposure, hazard and risk of alternative plasticizers to phthalate esters.

Alternative plasticizers to phthalate esters have been used for over a decade, but data regarding emissions, human exposure and health effects are limited. Here we review 20 alternative plasticizers in current use and their human exposure, hazard and risk. Physicochemical properties are collated for these diverse alternatives and log KOW values range over 15 orders of magnitude and log KAW and log KOA values over about 9 orders of magnitude. Most substances are hydrophobic with low volatility and are produced in high volumes for use in multiple applications. There is an increasing trend in the total use of alternative plasticizers in Sweden compared to common phthalate esters in the last 10 years, especially for DINCH. Evaluative indoor fate modeling reveals that most alternatives are distributed to vertical surfaces (e.g. walls or ceilings). Only TXIB and GTA are predicted to be predominantly distributed to indoor air. Human exposure data are lacking and clear evidence for human exposure only exists for DEHT and DINCH, which show increasing trends in body burdens. Human intake rates are collected and compared with limit values with resulting risk ratios below 1 except for infant's exposure to ESBO. PBT properties of the alternatives indicate mostly no reasons for concern, except that TEHPA is estimated to be persistent and TCP toxic. A caveat is that non-standard toxicological endpoint results are not available and, similar to phthalate esters, the alternatives are likely "pseudo-persistent". Key data gaps for more comprehensive risk assessment are identified and include: analytical methods to measure metabolites in biological fluids and tissues, toxicological information regarding non-standard endpoints such as endocrine disruption and a further refined exposure assessment in order to consider high risk groups such as infants, toddlers and children.