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Exposure related observations in humans: other data

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Administrative data

Endpoint:
exposure-related observations in humans: other data
Remarks:
potential occupational asthma cases
Type of information:
other: case study compilation
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Remarks:
Significant confounding factors were coexposure to other volatiles and various dusts; unclear inhalative exposure to HEMA and the pre-occupational clinical status of the majority of patients

Data source

Reference
Reference Type:
publication
Title:
Occupational respiratory hypersensitivity caused by preparations containing acrylates in dental personnel
Author:
Piirilä P, Kanerva H, Keskinen H, Estander T, Hytönen M, Tuppurainen M, Nordman H
Year:
1998
Bibliographic source:
Clin. Exp. Allergy 28, 1404-1411

Materials and methods

Type of study / information:
Case study compilation
Endpoint addressed:
respiratory sensitisation

Test material

Constituent 1
Chemical structure
Reference substance name:
2-hydroxyethyl methacrylate
EC Number:
212-782-2
EC Name:
2-hydroxyethyl methacrylate
Cas Number:
868-77-9
Molecular formula:
C6H10O3
IUPAC Name:
2-hydroxyethyl methacrylate

Method

Ethical approval:
not specified
Details on study design:
According to the authors: "Flow-volume spirometry was performed with a rolling seal spirometer (Mijnhardt, Vicalest 3) connected to a microcomputer (Medicro MR-3), and Viljanen's reference values were used. Histamine challenge tests were performed according Sovijarvi's method following FEV1 (Forced
expiratory volume in one second) values with a Vitalograph S bellow spirometer (Viralograph, Buckingham, UK). A 15% reduction in FEV 1 was considered significant and the provocative dose of histamine diphosphate causing a 15% reduction in FEY1 (PD15) was measured. The hyperresponsiveness was graded as strong with PD15 <0.10mg, moderate with 0.11-0.40mg and slight with 0.41 -1.6 mg.
The long-term peak expiratory flow (PEF) monitoring at the workplace and on days off was made
according to the method of Burge and the occupational effect was evaluated visually from the plotted presentation.
Sin prick test to common environmental allergens were performed using a previously described method. All patients were also tested with natural rubber latex gloves, and a commercial latex extract {Stallergenes S.A., Fresnes Cedex. France); tests with chloramine T were done if there was a positive work history also. Skin prick tests with methyl methacrylatc (MMA), 2-hydroxymethyl
methacrylate (2-HEMA), bisfenol-A-diglycidylether-mcthacrylate (BIS-GMA}, ethyleneglycol dimethacrylate (EGDMA) and triethyleneglycol dimethacrylate (TREGDMA) were done with human serum albumin (HSA) conjugates as previously described.
The skin patch tests to acrylates were done with the occlusive Finn Chamber(R) technique.
Inhalation challenge tests with a placebo and dental acrylate compounds {mixtures in liquid or powder form) were performed in a 6 m3 challenge chamber according to the international guidelines. If the acrylate compound was in liquid form, the patient handled the compound
for 30 min as follows: six drops of the dental primer and 6 drops of the dental adhesive were added simultaneously for 10 min; two drops of each were then added in turn for 5 min and repeated once. If the challenge test was negative, the challenge test was repeated on another day with a double dose of both substances. The control challenge test was done with polyol (Hydrogenated decene oligorners, Nexbase 200 6FG, Neste PAO NV, Beringen, Belgium} if the agent tested was in fluid form and with lactose if it was in powder form.
The FEV1 and PEF values during the challenge test procedure were measured by a portable pocket-size spirometer {Micro Plus Spirometer, Micro Medical, UK). In case of patients 1 and 2. the PEF values were followed up with a Wright peak flow meter (Clement Clarke M286, Ferraris
Medical) and the FEV I values with a Vitalograph S bellow spirometer (Yitalograph, Buckingham, UK) according to a method reported earlier. The clinical symptoms and lung auscultation were recorded as well.
The mucosal response of the nose during the challenge tests was registered and nasal blockage and rhinorrhoea were scored before and after the provocation test according to a method by Hytonen and Sala. Physiological measurements were also used in the recording of the change in the nasal blockage either by rhinomanometry (Rhinomanometer NRG. Mercury Electronics, Glasgow, UK) or acoustic rhinometry (RHIN2000, SR Electronics APS, Lynge, Denmark). The nasal response was considered positive if the status change and physiological measurement criteria were fulfilled. A scoring method was used in che evaluation of the laryngeal and pharyngeal response. The ocular reaction was followed and evaluated by an ophthalmologist as described
earlier.
Exposure assessment:
not specified
Remarks:
Inhalative exposure to HEMA or any other substance was not determined, neither in the occupational setting nor in the challenge test, and just assumed based on the use of the mixed dental products.

Results and discussion

Results:
see overall remarks

Applicant's summary and conclusion

Conclusions:
The reported clinical cases suffer from a consistent picture in terms of medical diagnosis that would allow to conclude on a typical mode of action for these substances (e.g. heterogeneous IgE and SIC pattern). On substance level, the specificity is rated low as only mixed exposure was investigated, in the occupational setting as well as in the SIC tests. Given the low vapour pressure of the substances, and as consequence the partially unknown respiratory exposure in general, a low biological plausibility is assigned. Overall, a low level of confidence and a high level of uncertainty is considered for these cases to provide evidence that HEMA is a respiratory sensitiser.
Executive summary:

Seven cases, thereof 5 dental nurses and 2 dentists, were identified from the dental sector. In 6 of those, OA was diagnosed, in the 7th case rhinitis. Based on the case descriptions, occupational exposure to HEMA is considered as likely, but not to HPMA. There is relevant co-exposure to other substances that are contained in dental products used as primer and adhesives, predominantly bis-GMA but also inorganic material like quartz, Alumina or silica. With exception of case #7, all patients had a clinical history that indicate immunologic hypersensitivity (atopy – individual or in the family) or respiratory hypersensitivity (unspecific bronchial hyperreactivity). The IgE responses (unspecific indicator for immune-based mechanisms; only tested with the Piirilä patients), were heterogenous with four cases without increase and 3 with increase. SIC tests were performed in 7 cases with the HEMA containing dental primers and/ or adhesives and thus with mixtures, by repeating typical dental handling routines during the SIC. Like the IgE responses, the SIC responses were heterogeneous, with 3 LAR, 3 EAR and one negative test. Regarding the ECHA R.7a requirements, the majority of information was not available to assess the cases.


The cases were assessed in a formal WoE assessment on the respiratory sensitisation potential of HEMA and HPMA as attached to the dossier; the summary of this assessment is available in the endpoint summary of the chapter "Sensitisation".