Skin Exposure Contributes to Chemical-Induced Asthma: What is the Evidence? A Systematic Review of Animal Models

It is generally assumed that allergic asthma originates primarily through sensitization via the respiratory mucosa, but emerging clinical observations and experimental studies indicate that skin exposure to low molecular weight (LMW) agents, i.e. “chemicals,” may lead to systemic sensitization and subsequently develop asthma when the chemical is inhaled. This review aims to evaluate the accumulating experimental evidence that adverse respiratory responses can be elicited upon inhalation of an LMW chemical sensitizer after previous sensitization by dermal exposure. We systematically searched the PubMed and Embase databases up to April 15, 2017, and conducted forward and backward reference tracking. Animal studies involving both skin and airway exposure to LMW agents were included. We extracted 6 indicators of “selective airway hyper-responsiveness” (SAHR)—i.e. respiratory responses that only occurred in previously sensitized animals—and synthesized the evidence level for each indicator into strong, moderate or limited strength. The summarized evidence weight for each chemical agent was graded into high, middle, low or “not possible to assess.” We identified 144 relevant animal studies. These studies involved 29 LMW agents, with 107 (74%) studies investigating the occurrence of SAHR. Indicators of SAHR included physiological, cytological/histological and immunological responses in bronchoalveolar lavage, lung tissue and airway-draining lymph nodes. Evidence for skin exposure-induced SAHR was present for 22 agents; for 7 agents the evidence for SAHR was inconclusive, but could not be excluded. The ability of a chemical to cause sensitization via skin exposure should be regarded as constituting a risk of adverse respiratory reactions.

Skin Exposure Contributes to Chemical-Induced Asthma: What is the Evidence? A Systematic Review of Animal Models

It is generally assumed that allergic asthma originates primarily through sensitization via the respiratory mucosa, but emerging clinical observations and experimental studies indicate that skin exposure to low molecular weight (LMW) agents, i.e. “chemicals,” may lead to systemic sensitization and subsequently develop asthma when the chemical is inhaled. This review aims to evaluate the accumulating experimental evidence that adverse respiratory responses can be elicited upon inhalation of an LMW chemical sensitizer after previous sensitization by dermal exposure. We systematically searched the PubMed and Embase databases up to April 15, 2017, and conducted forward and backward reference tracking. Animal studies involving both skin and airway exposure to LMW agents were included. We extracted 6 indicators of “selective airway hyper-responsiveness” (SAHR)—i.e. respiratory responses that only occurred in previously sensitized animals—and synthesized the evidence level for each indicator into strong, moderate or limited strength. The summarized evidence weight for each chemical agent was graded into high, middle, low or “not possible to assess.” We identified 144 relevant animal studies. These studies involved 29 LMW agents, with 107 (74%) studies investigating the occurrence of SAHR. Indicators of SAHR included physiological, cytological/histological and immunological responses in bronchoalveolar lavage, lung tissue and airway-draining lymph nodes. Evidence for skin exposure-induced SAHR was present for 22 agents; for 7 agents the evidence for SAHR was inconclusive, but could not be excluded. The ability of a chemical to cause sensitization via skin exposure should be regarded as constituting a risk of adverse respiratory reactions.

Occupational Exposure to Metals in Shooting Ranges: A Biomonitoring Study

BACKGROUND: Lead (Pb) exposure in shooting ranges has been reduced by various measures such as jacketed ammunition and lead-free primers. Nevertheless, this may lead to exposure to other metals, potentially resulting in adverse health effects. METHODS: In a cross-sectional study, 35 subjects from seven different shooting ranges were studied: four shooting instructors, 10 police officers, 15 Special Forces, and six maintenance staff members. Metals and metalloids were determined in blood and urine by inductively coupled plasma–mass spectrometry. RESULTS: The concentrations of most elements did not differ significantly between groups or compared to reference values, except for Sb and Pt in urine and Pb in blood. Mean values for Sb were considerably higher in urine from the Special Forces (0.34 μg/L), the maintenance staff (0.13 μg/L), and shooting instructors (0.32 μg/L) compared to the police officers before shooting (0.06 μg/L) and a Belgian reference value (0.04 μg/L). For Pt, the Special Forces showed higher mean urinary concentrations (0.078 μg/L) compared to a Belgian reference value (<0.061 μg/L). Mean values for blood lead were markedly higher in the Special Forces (3.9 μg/dL), maintenance staff (5.7 μg/dL), and instructors (11.7 μg/dL) compared to police officers (1.4 μg/dL). One instructor exceeded the biological exposure index for blood Pb (38.8 μg/dL). CONCLUSION: Since both Pb and Sb were found to be higher in shooting range employees, especially among frequent shooters, it is advisable to provide appropriate protective equipment, education, and medical follow-up for shooting range personnel in addition to careful choice of ammunition.

Determinants of bisphenol A and phthalate metabolites in urine of Flemish adolescents.

As part of the second Flemish Environment and Health Study (FLEHS II), bisphenol-A (BPA) and different phthalate metabolites were analyzed, for the first time, in the urine of 210 adolescents in Flanders, Belgium. All chemicals had a detection frequency above 90%. For all compounds, except the sum of DEHP, highest levels were detected during spring. Average values for the Flemish adolescents were in an agreement with concentrations found in different international studies, all confirming the ubiquity of BPA and phthalate exposure. There was a significant correlation between BPA and the different phthalate metabolites (r between 0.26 and 0.39; p<0.01). Shared sources of exposure to BPA and phthalates, such as food packaging, were suggested to be responsible for this positive correlation. Different determinants of exposure were evaluated in relation to the urinary concentrations of these chemicals. For BPA, a significant association was observed with household income class, smoking and exposure to environmental tobacco smoke. For phthalates, the following significant associations were observed: age (MBzP), educational level of the adolescent (MBzP), equivalent household income (MnBP), use of personal care products (MnBP and MBzP), wall paper in house (MnBP and MBzP) and use of local vegetables (MnBP and MBzP).

Biomarkers of human exposure to personal care products: results from the Flemish Environment and Health Study (FLEHS 2007-2011).

Personal care products (PCPs), such as soaps, perfumes, cosmetics, lotions, etc., contain a variety of chemicals that have been described as potentially hormone disrupting chemicals. Therefore, it is important to assess the internal exposure of these chemicals in humans. Within the 2nd Flemish Environment and Health Study (FLEHS II, 2007-2011), the human exposure to three classes of pollutants that are present in a wide variety of PCPs--i.e. polycyclic musks (galaxolide, HHCB and tonalide, AHTN in blood), parabens (urinary para-hydroxybenzoic acid, HBA) and triclosan (urinary TCS)--was assessed in 210 Flemish adolescents (14-15 years) and in 204 adults (20-40 years) randomly selected from the general population according to a stratified two stage clustered study design. The aim of this study was to define average levels of exposure in the general Flemish population and to identify determinants of exposure. Average levels (GM (95% CI)) in the Flemish adolescents were 0.717 (0.682-0.753) µg/L for blood HHCB; 0.118 (0.108-0.128) µg/L for blood AHTN; 1022 (723-1436) µg/L for urinary HBA and 2.19 (1.64-2.92) µg/L for urinary TCS. In the adults, levels of HBA were on average 634 (471-970) µg/L. Inter-individual variability was small for HHCB and AHTN, intermediate for HBA, and large for TCS. All biomarkers were positively associated with the use of PCPs. Additionally, levels of HHCB and AHTN increased with higher educational level of the adolescents. Both in adults and adolescents, urinary HBA levels were negatively correlated with BMI. We define here Flemish exposure values for biomarkers of PCPs, which can serve as baseline exposure levels to identify exposure trends in future biomonitoring campaigns.