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Toxicological information

Exposure related observations in humans: other data

Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
other: not applicable
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Human workplace investigation, no restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
publication
Title:
Visual and ocular changes associated with exposure to two tertiary amines
Author:
Page EH, Cook CK, Hater MA, Mueller CA, Grote AA and Mortimer VD
Year:
2003
Bibliographic source:
Occup Environ Med; 60: 69-75

Materials and methods

Type of study / information:
Published information on a health hazard evaluation of a label printing company performed by the National Institute for Occupational Safety and Health (NIOSH). Goal was to determine if exposure to dimethylisopropanolamine (DMIPA) and dimethylaminoethanol (DMAE) was associated with visual disturbances and/or ocular changes.
Endpoint addressed:
eye irritation
Principles of method if other than guideline:
Questionnaires, eye examinations (visual acuity, contrast sensitivity at 2.5% and 1.25% contrast, slit lamp biomicroscopy, and pachymetry), and industrial hygiene monitoring of the substances under investigation were performed in a label printing plant over a two week period.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
1-(dimethylamino)propan-2-ol
EC Number:
203-556-4
EC Name:
1-(dimethylamino)propan-2-ol
Cas Number:
108-16-7
Molecular formula:
C5H13NO
IUPAC Name:
1-(dimethylamino)propan-2-ol
Test material form:
liquid
Specific details on test material used for the study:
- Name of test material (as cited in article): dimethylisopropanolamine (DMIPA)

Method

Details on study design:
INDUSTRIAL HYGIENE MONITORING
For eight workdays comprehensive industrial hygiene monitoring was performed to assess workers' full shift and short-term exposures to DMIPA and DMEA. A total of 108 full shift personal breathing zone (PBZ) air samples for the amines were collected, 93 in the line division and 15 in the prime division. Twelve area air samples were collected in the office area of the plant and outdoors. Each air sample was collected on an XAD-7 tube connected to air sampling pumps pre- and post-calibrated at 100 cc/min of air per min. In accordance with NMAM No. 2007, each sample collected was analysed for both DMIPA and DMEA by gas chromatography equipped with a flame ionisaton detector.

VENTILATION
A qualitative assessment of the ventilation system was performed by releasing a glycol based aerosol “fog” from the new exhaust discharge location on top of the roof on the north side of the building and from below the roof line, high on the north outside wall of the building, simulating the previous exhaust discharge location. The fog was observed and videotaped. A tracer gas study was conducted to quantitatively determine if exhaust re-entered the plant through air intake grilles located close to the exhaust discharges on the north side of the building. Ten MIRAN-203 infrared specific vapour analysers, three B&K-1302 photoacoustic infrared multi-gas monitors, and an INOVA-1312 photoacoustic multi-gas monitor were positioned inside the plant. Six instruments (four MIRANs, a B&K, and the INOVA) were placed at widely separated locations in the line division, one MIRAN was located in the office area, two MIRANs were placed near the shredder/ compactors in the warehouse area, one MIRAN was placed in the ink area, and two MIRANs and a B&K were set up in the prime division. One B&K multi-gas monitor was used for mobile monitoring wherever needed. A low toxicity gas, sulphur hexafluoride (SF6) was then released first from the opening of one of the curved exhaust discharges on the roof, then from the previous exhaust discharge location on the side of the building. Tracer gas was also used inside the building to assess the transport and dispersion contaminants in the line division. With the instruments in the same locations as described above, SF6 was released from a location under one of the supply air inlets in the south centre of the room to simulate re-entry of previously exhausted air. The concentrations recorded by the instruments were stored in a digital format to be analysed later, both tabulated on computer spreadsheets and visualised on concentration versus time charts. Starting with the known time of SF6 release, the visualised concentration charts were inspected for any increases that could be identified as coming from the released SF6. If peaks were identified, the time between the release of SF6 and the appearance of the peak was noted, as was the duration and magnitude of the peak.

MEDICAL
All employees in the line division of the plant were recruited to take part in the evaluation. All participants gave written informed consent. Those who were wearing contact lenses at the time of the evaluation were not eligible to participate because of the possibility of absorption of the chemicals into the contacts and because contact lenses can cause changes in the corneal epithelium.6 Workers were informed of this in advance so they could discontinue contact lens use in order to participate, if desired. The medical evaluation consisted of a baseline questionnaire to determine whether the worker had blurred or foggy vision, halo vision, or blue-grey vision in the past year, if these symptoms were accompanied by eye irritation, and if they caused difficulty working or driving home. A history of eye disease or injury was obtained as well. The same baseline questionnaire was administered to workers in the prime division. Workers in the prime division who reported having experienced blurred, halo, or blue-grey vision in the past were asked to participate in the study. Eye examinations were performed each day from Monday to Thursday at the beginning and end of both shifts. The examination consisted of visual acuity, contrast sensitivity at 2.5% and 1.2% contrast, ultrasonic pachymetry to determine corneal thickness, and a slit lamp examination to determine the presence of corneal opacity. Visual acuity and contrast sensitivity were performed at a distance of 10 feet with a luminance level of 125 candelas per square metre (Precision Vision, LaSalle, Illinois). A loss of at least one line or row on the chart was considered a reduction in visual acuity or contrast sensitivity. Corneal thickness was performed using an ultrasonic pachymeter (Sonomed, Inc., Micropach model 200P) reported in mm. Corneal opacity was graded on a scale of 0 (normal or clear), 1 (minimal/mild opacity), 2 (moderate opacity), and 3 (marked opacity).6 The slit lamp examinations and pachymetry were conducted by a board certified ophthalmologist. Employees were administered a brief questionnaire at each examination documenting current symptoms. The visual test examiners were unaware of current visual symptoms of employees.

STATISTICAL ANALYSIS
SAS version 8.1 software (SAS Institute, Cary, North Carolina) was used for the statistical analyses. SAS Proc Mixed, which can take into account the multiple measures for some subjects, was used to compare amine exposure means for those in the line and prime divisions, and for those with and without visual symptoms/signs. A p value of <0.05 was considered statistically significant. SAS Proc Genmod, which also handles repeated measures for subjects, was used to perform logistic regression analyses. Logistic regression was used to examine possible relations between visual symptoms/signs and the amine exposure levels. The OR reflects a per unit increase of 1 mg/m3 in amine concentration. The logistic regression analyses generated an odds ratio (OR) as a measure of association. Odds ratios greater than one indicate a positive relation between a symptom/sign and an amine exposure level. Together with the OR, a 95% confidence interval (CI) for the OR was calculated. The OR is considered statistically significant if the 95% CI does not include the number one.
Exposure assessment:
measured
Details on exposure:
TYPE OF EXPOSURE MEASUREMENT
monitoring was performed to assess workers’ full shift and short term exposures to DMIPA and DMAE. A total of 108 full shift personal breathing zone (PBZ) air samples for the amines were collected, 93 in the line division and 15 in the prime division. Twelve area air samples were collected in the office area of the plant and outdoors. Each air sample was collected on an XAD-7 tube connected to air sampling pumps pre- and post-calibrated at 100 cc/min of air per min. In accordance with NMAM No. 2007, each sample collected was analysed for both DMIPA and DMAE by gas chromatography equipped with a flame ionisation detector.

EXPOSURE LEVELS
The mean TWA concentration of DMIPA was significantly higher in the line division than in the prime division (7.70 v 2.08 mg/m3, p < 0.01), as was the mean TWA concentration for total amines (9.96 v 5.56 mg/m3, p < 0.01). The mean TWA concentration of DMAE was higher in the prime division than the line division (3.47 v 2.27 mg/m3, p < 0.01). Total amine TWA concentrations in the office areas ranged from 0.2 to 1.9 mg/m3 and were non-detectable outdoors.

Results and discussion

Results:
Eighty nine percent of line workers reported having experienced blurry vision while at work in the past 12 months, compared to 12.5% of prime workers. The mean time weighted average (TWA) concentration of DMIPA was significantly higher in the line division than in the prime division, as was the mean TWA concentration for total amines. The mean TWA concentration of DMEA was higher in the prime division than the line division. Higher levels of total amines were associated with increased risk of reporting blurry vision, halo vision and blue-grey vision. The risk of corneal opacity rose with increasing exposure to total amines. The prevalence of corneal opacity also increased with increasing concentration of total amines. Median corneal thickness increased with increasing grades of corneal opacity. There was a statistically significant relation between total amine concentration and increased risk of reduced bilateral visual acuity and 2.5% contrast sensitivity.

Applicant's summary and conclusion