Axel Hahn

Assessment of Early Acute Lung Injury in Rats Exposed to Aerosols of Consumer Products: Attempt to Disentangle the “Magic Nano” Conundrum

In Germany in 2006 a series of rapidly developing and sometimes severe cases of pulmonary health impairment were observed after normal use of the “Magic Nano Glass & Ceramic” spray and “Magic Nano Bath” spray. In contrast, the previously marketed “Magic Nano” pump spray product (handheld trigger device without propellants) was unobtrusive. Analysis of particles discharged from these products did not reveal stable (solid) nano-sized particles. The precipitous increase of pulmonary health impairment in humans caused by “Magic Nano Sprays” triggered a comparative assessment of the acute inhalation toxicity of “Magic Nano Glass & Ceramic” spray, “Magic Nano Bath” spray, and “Magic Nano” pump spray in rats. The first two test specimens were examined as spray-can aerosols using an intermittent generation principle, whereas the undiluted liquid content of the pump spray was continuously aerosolized. Groups of Wistar rats were nose-only exposed for 4 h. However, due to mortality occurring already during exposure following exposure to Glass & Ceramic spray, the exposure duration was reduced to ∼ 2 h in some groups. In addition to endpoints called for by contemporary testing guidelines, respiratory tract injury was also probed by respiratory function measurements during exposure supplemented by analyses in bronchoalveolar lavage (BAL) fluid on the first postexposure day, including lung histopathology in rats exposed to Glass & Ceramic spray. The Glass & Ceramic spray caused mortality at 2269 mg/m3 and above, the pump spray was in the beginning lethal range at 81222 mg/m3, while the bath spray was tolerated without mortality up to the maximum tested nominal concentrations of 28100 mg/m3. The time-adjusted 4-h LC50 of Glass & Ceramic spray was 5098 mg/m3. The analysis of respiratory patterns revealed changes indicative of both upper and lower respiratory tract sensory irritation. In addition to clinical signs suggestive of marked lung irritation, especially in the rats exposed to the Glass & Ceramic spray, histopathology revealed lung inflammation, hemorrhages, edema, and focal septal thickening. Lung weights and BAL endpoints (lactate dehydrogenase [LDH], protein, γ -glutamyltransaminase, and neutrophilic granulocytes) were markedly increased. In summary, this comparative study demonstrates that the conventional OECD 403 protocol is suitable to comparatively assess the potential and potency of these types of consumer products in their end-use configuration. Measurements in BAL were most suitable for the identification of acute lung injury. By contrast, lung function measurements during exposure did not demonstrate any conclusive association with lung injury. It does not appear that the particle size per se is a key determinant in the toxicity of “Magic Nano Glass & Ceramic” spray (approximately 100% mortality occurred at a MMAD of ∼ 7 μ m; GSD ≈ 3). This might suggest that more volatile substances or substances contained in the test articles that co-evaporate with solvents or water may be causative for the findings observed. Hence, the findings of this study support the notion that the assessment of the acute inhalation toxicity of complex end-use products is methodologically challenging and cannot be readily anticipated based on compositional or physical (particle size) data. Accordingly, in the absence of predictive and validated in vitro assays, in vivo inhalation testing of potentially toxic commercialized spray products appears to be indispensable for consumer safety. In order to prevent indiscriminant testing of such products in bioassays, the development of standardized in vitro alternatives should be considered with high priority.

Expert judgement of poisonings and human biomonitoring - The BfR three-level and matrix model

German physicians are obligated (Para 16e Chemicals Law) to submit essential data on poisonings to the Centre for Documentation and Assessment of Poisonings at the Federal Institute for Risk Assessment (Bundesinstituts für Risikobewertung, BfR). In addition, German poison centres are subjected to compulsory reporting of their findings of general importance gained in the context of their activities. The BfR assessment of poisonings has important significance for human case data collection, risk identification, and German toxicological monitoring. Using more than 60,000 reports on cases of poisoning, the BfR developed a structured expert judgement trial for poisonings. This judgement is based on a three-level model, accompanied by two different matrix procedures for an enhanced and more exact assessment of the exposures and the causality between health impairment and exposure. Particularly for low-dose exposures, human biomonitoring data is extremely valuable for the assessment process. Especially in chronic low-dose level exposures, the scientific assessment of related health impairments is often not possible without existing human biomonitoring data. For the future improvement of public health related to poisonings, ingestions by children, workplace chemical exposures, and incidents, we have to establish a nation-wide programme for monitoring human exposures which keeps pace with the progressive production of new chemicals. This must be done in close co-operation with physicians, poison centres, government safety organisations, and environmental health specialists and must be based on proven expert judgement tools and available human biomonitoring data.

Risikomanagement bei Lampenölvergiftungen in Deutschland

Seit 1954 wird in der wissenschaftlichen Literatur regelmiifgig und zunehmend a chemische Pneumonien und auch Todesfiille bei Petroleumdestillatingestionen ira Kindesalter berichtet (Ubers. 1). In den USA sind diese UnfS.lle sogar der Hauptgrund fa Krankenhausaufnahmen durch Haushaltschemikalien mit schwerwiegenden Gesundheitsst6rungen ira Kindesalter. Vergleichbare Erfahrungen gibt es auch in Afrika, Asien und Europa.

Vergiftungen in Deutschland

Cases of poisoning account for a distinct share of accidents in Germany, which is particularly high for accidents involving children. Cases of poisoning resulting from suicidal intent or abuse are not counted as accidents. Compared to other cases of disease and accidents, the numerical documentation of cases of poisoning is inadequate. Presently, there is no institution in Germany that could make available representative and meaningful data on the current state of poisoning. Owing to intensive scientific cooperation between the poison information centers (funded by the federal states) and the Poison and Product Documentation Center at the Federal Institute for Risk Assessment (BfR DocCenter) as well as to international cooperation, harmonized and standardized tools have been developed for the appropriate documentation and reporting of procedures to account for poisoning accidents. The first evaluation for 2005-2012 based on published and processed figures for the Federal Republic of Germany yielded the following results: Of approximately 230,000 telephone inquiries received in 2012, about 207,000 involved exposure of humans to different noxae. An annual increase of 3-5 % was recorded. For 2011, analyses of subsets processed by means of standardized methods yielded the following results: Medicines were involved in about 39 % of the cases recorded (of these, medicinal products for humans in 99 %); chemical/physicochemical agents in about 26 % (of these, cleaning and maintenance products in 46 %); products of daily use in about 14 % (of these, cosmetics in 40 %); and plants in about 10 %. More than 90 % of cases were acute poisoning and less than 5 %, chronic poisoning. Regarding the degree of severity of poisoning, an asymptomatic course was reported for 44 % of the cases; minor manifestations were experienced in 30 %, moderate ones in 6 %, and severe manifestations in 2 % of the cases recorded. Fatal cases were rare (< 0.1 %). The majority of cases (67 %) were caused by poisoning accidents, followed by suicidal action (20 %), with abuse and industrial poisoning (4 %) in third position; 1 % of the cases of poisoning were attributed to adverse drug reactions (ADR) and mistaking a medicinal product for another one. Infants aged 1-2 years have the highest risk of poisoning. A panel of the BfR Committee for the Assessment of Poisonings has already developed proposals for a national monitoring scheme of poisoning incidents. The aim is to prepare annual reports similar to the report of the National Poison Data System (NPDS) maintained by the American Association of Poison Control Centers (AAPCC) in the USA.

Vergiftungen in Deutschland@@@Cases of poisoning in Germany: Krankheitsbegriff, Dokumentation und Einblicke in das Geschehen@@@Disease entity, documentation, and aspects of the event

Cases of poisoning account for a distinct share of accidents in Germany, which is particularly high for accidents involving children. Cases of poisoning resulting from suicidal intent or abuse are not counted as accidents. Compared to other cases of disease and accidents, the numerical documentation of cases of poisoning is inadequate. Presently, there is no institution in Germany that could make available representative and meaningful data on the current state of poisoning. Owing to intensive scientific cooperation between the poison information centers (funded by the federal states) and the Poison and Product Documentation Center at the Federal Institute for Risk Assessment (BfR DocCenter) as well as to international cooperation, harmonized and standardized tools have been developed for the appropriate documentation and reporting of procedures to account for poisoning accidents. The first evaluation for 2005-2012 based on published and processed figures for the Federal Republic of Germany yielded the following results: Of approximately 230,000 telephone inquiries received in 2012, about 207,000 involved exposure of humans to different noxae. An annual increase of 3-5 % was recorded. For 2011, analyses of subsets processed by means of standardized methods yielded the following results: Medicines were involved in about 39 % of the cases recorded (of these, medicinal products for humans in 99 %); chemical/physicochemical agents in about 26 % (of these, cleaning and maintenance products in 46 %); products of daily use in about 14 % (of these, cosmetics in 40 %); and plants in about 10 %. More than 90 % of cases were acute poisoning and less than 5 %, chronic poisoning. Regarding the degree of severity of poisoning, an asymptomatic course was reported for 44 % of the cases; minor manifestations were experienced in 30 %, moderate ones in 6 %, and severe manifestations in 2 % of the cases recorded. Fatal cases were rare (< 0.1 %). The majority of cases (67 %) were caused by poisoning accidents, followed by suicidal action (20 %), with abuse and industrial poisoning (4 %) in third position; 1 % of the cases of poisoning were attributed to adverse drug reactions (ADR) and mistaking a medicinal product for another one. Infants aged 1-2 years have the highest risk of poisoning. A panel of the BfR Committee for the Assessment of Poisonings has already developed proposals for a national monitoring scheme of poisoning incidents. The aim is to prepare annual reports similar to the report of the National Poison Data System (NPDS) maintained by the American Association of Poison Control Centers (AAPCC) in the USA.

Vergiftungen in Deutschland : Krankheitsbegriff, Dokumentationund Einblicke in das Geschehen

Cases of poisoning account for a distinct share of accidents in Germany, which is particularly high for accidents involving children. Cases of poisoning resulting from suicidal intent or abuse are not counted as accidents. Compared to other cases of disease and accidents, the numerical documentation of cases of poisoning is inadequate. Presently, there is no institution in Germany that could make available representative and meaningful data on the current state of poisoning. Owing to intensive scientific cooperation between the poison information centers (funded by the federal states) and the Poison and Product Documentation Center at the Federal Institute for Risk Assessment (BfR DocCenter) as well as to international cooperation, harmonized and standardized tools have been developed for the appropriate documentation and reporting of procedures to account for poisoning accidents. The first evaluation for 2005-2012 based on published and processed figures for the Federal Republic of Germany yielded the following results: Of approximately 230,000 telephone inquiries received in 2012, about 207,000 involved exposure of humans to different noxae. An annual increase of 3-5 % was recorded. For 2011, analyses of subsets processed by means of standardized methods yielded the following results: Medicines were involved in about 39 % of the cases recorded (of these, medicinal products for humans in 99 %); chemical/physicochemical agents in about 26 % (of these, cleaning and maintenance products in 46 %); products of daily use in about 14 % (of these, cosmetics in 40 %); and plants in about 10 %. More than 90 % of cases were acute poisoning and less than 5 %, chronic poisoning. Regarding the degree of severity of poisoning, an asymptomatic course was reported for 44 % of the cases; minor manifestations were experienced in 30 %, moderate ones in 6 %, and severe manifestations in 2 % of the cases recorded. Fatal cases were rare (< 0.1 %). The majority of cases (67 %) were caused by poisoning accidents, followed by suicidal action (20 %), with abuse and industrial poisoning (4 %) in third position; 1 % of the cases of poisoning were attributed to adverse drug reactions (ADR) and mistaking a medicinal product for another one. Infants aged 1-2 years have the highest risk of poisoning. A panel of the BfR Committee for the Assessment of Poisonings has already developed proposals for a national monitoring scheme of poisoning incidents. The aim is to prepare annual reports similar to the report of the National Poison Data System (NPDS) maintained by the American Association of Poison Control Centers (AAPCC) in the USA.