Occupational asthma from sensitisation to 4,4-methylene-bismorpholine in clean metalworking fluid

Walters, Gareth; Moore, Vicky; Robertson, Alastair; McGrath, Emmet E.; Parkes, Edward; Burge, Peter

doi:10.1183/09031936.00036313

Cited by 7 publications

(3 citation statements)

References 16 publications

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“…Agius et al [38] have developed and validated a quantitative structure-activity relationship model to predict the potential of LMW organic agents to cause asthma due to sensitization, as determined by the hazard index [39,40]. This model was applied in the case of IOA to a biocide as described by Walters et al [19], the occupational hazard index of 4,4-methylene-bismorpholine reaching 0.95; comparatively, diisocyanates, the most frequent cause of occupational asthma in industrialized countries, have an hazard index of 1 [41]. However, even with a hazard index of 1, chlorhexidine is an uncommon cause of IOA probably because of the nature of its exposure as it is less aerosolized in vapor form than diisocyanates.…”

Section: Reversible Airflow Obstructionmentioning

confidence: 99%

“…SICs are considered the reference standard for the diagnosis of occupational asthma, and, when done in the laboratory, they allow identification of the responsible agent [1,7,8]. [18][19][20] lists all new causes of IOA according to their molecular weight, that is, high (>5-10 kD, usually a protein or glycopeptide) or low, as well as the type of job involved (workplace setting), the number of subjects and their clinical characteristics (age, sex, atopic status, and smoking history when known), associated work-related symptoms (rhinoconjunctivitis and contact urticaria or dermatitis), immunological findings specific to the relevant agent (SPT and sIgE) when done, functional tests used to confirm the diagnosis of asthma (defined by variable airflow obstruction or increased BHR) and work relatedness including monitoring of PEFs at and off work, and finally results of SICs.…”

Section: New Agentsmentioning

confidence: 99%

“…The majority of new causes of IOA were seen with high molecular agents: new enzymes used as detergents [11 && ,12] or food additives [13], arthropods contaminating food (cured ham) [14], earthworms used as aquarium fish food [15 && ], and orange fruit [tree aeroallergen [16] and flavedo (zest) [17 & ]], and only three agents having a low molecular weight (LMW) (spruce wood dust [18], the biocide 4,4-methylene-bismorpholine [19], and the halogenated platinum compound K 2 PtCL 4 [20]). Although savinase is not a truly new agent as it belongs to the subtilisin family, like other enzymes such as maxatase or alcalase, the cases presented here [11 && ,12] were the first cases described with this specific protease enzyme derived from Bacillus amyloliqefaciens.…”

Section: New Agentsmentioning

confidence: 99%

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New causes of immunologic occupational asthma, 2012–2014

Cartier¹

2015

Current Opinion in Allergy &Amp; Clinical Immunology

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There are more than 400 known causes of IOA and the list grows continuously with the development of new technologies and better recognition of the diagnosis by physicians. IgE-mediated sensitization was confirmed in all new cases involving high-molecular-weight agents and in two of the three new cases involving low-molecular-weight agents. Symptoms of rhinitis were often associated with both types of agents. Physicians should stay alert and suspect occupational asthma in any adult with new-onset asthma or with newly uncontrolled asthma.

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Section: Reversible Airflow Obstructionmentioning

confidence: 99%

Section: New Agentsmentioning

confidence: 99%

Section: New Agentsmentioning

confidence: 99%

See 1 more Smart Citation

New causes of immunologic occupational asthma, 2012–2014

Cartier¹

2015

Current Opinion in Allergy &Amp; Clinical Immunology

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Bis(morpholino)methan [MAK Value Documentation in German language, 2018]

Hartwig¹,

Arand²

2018

The MAK‐Collection for Occupational Health and Safety

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The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated 4,4′‐methylenedimorpholine [ 5625‐90‐1 ], considering all toxicological endpoints. Available publications and unpublished study reports are described in detail. 4,4′‐Methylenedimorpholine is a formaldehyde releaser. The substance is corrosive to rabbit skin and induces local effects in the forestomach of rats after prolonged oral application. Therefore, the critical effect is presumably the local irritation in the respiration tract. Adequate data in humans and inhalation studies in animals to derive a maximum concentration at the work place (MAK value) is not available. Thus, the assignment of the substance to Section II b of the List of MAK and BAT Values is retained. A prenatal toxicity study in rabbits does not show any developmental toxicity up to the highest dose tested of 100 mg/kg body weight and day. 4,4′‐Methylenedimorpholine induces mutations in bacteria and is mutagenic and predominantly clastogenic to mammalian cells. The clastogenicity has, however, not been confirmed in vivo. Adequate carcinogenicity studies with 4,4′‐methylenedimorpholine are not available but the release of the local carcinogen formaldehyde has also to be taken into account for evaluating the carcinogenicity of 4,4′‐methylenedimorpholine. At work places where 4,4′‐methylenedimorpholine is used the mean air concentration of formaldehyde is about 2 µl/m 3 . As the difference between the MAK value of formaldehyde of 300 µl/m 3 and the work place air concentration is sufficiently large, and the measured concentrations are in the range of the background levels, no classification into a Carcinogen Category is confirmed. Clinical data in humans reveal a skin sensitizing potential which is also due to the release of formaldehyde. The results of the animal experiments are negative but they are carried out at very low concentrations. 4,4′‐Methylenedimorpholine is designated with an “Sh” notation. Skin contact is not expected to contribute significantly to systemic toxicity.

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Hypersensitivity Pneumonitis Due to Metalworking Fluid Aerosols

Burge

2016

Curr Allergy Asthma Rep

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Metalworking fluid exposure has become the commonest recognised cause of occupational hypersensitivity pneumonitis, having been rare before 2000. There are many possible agents in the metalworking fluid which may be the cause of disease including bacteria, mycobacteria, fungae, biocides, emulsifiers, reodorants and dissolved chrome and cobalt. Causes are likely to be different in different outbreaks. Mycobacteria growing in the metalworking fluid have generated immune responses in some workers, but their role in disease causation is not yet established. Many outbreaks have been identified in large workplaces using common sumps. It is not possible to prevent microbial contamination of metalworking fluids in use. Disease prevention should focus on stopping inhalation of aerosols, particularly by re-engineering to remove recirculation.

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Occupational asthma from sensitisation to 4,4-methylene-bismorpholine in clean metalworking fluid

Cited by 7 publications

References 16 publications

New causes of immunologic occupational asthma, 2012–2014

New causes of immunologic occupational asthma, 2012–2014

Bis(morpholino)methan [MAK Value Documentation in German language, 2018]

Hypersensitivity Pneumonitis Due to Metalworking Fluid Aerosols

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