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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
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well reported study which contains key details and adheres to good scientific principles

Data source

Reference
Reference Type:
publication
Title:
Follow up study of haematological effects in workers exposed to 2-methoxyethanol
Author:
Shih TS, Hsieh AT, Chen YH, Liao GD, Chen CY, Chou JS, Liou SH
Year:
2003
Bibliographic source:
Occup Env Med 60, 130-5

Materials and methods

Endpoint addressed:
repeated dose toxicity: inhalation
Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
To examine the association between occupational full shift exposure and haematological effects and their reversibility before and after implementation of exposure risk reduction measures
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Exposure to glues contains 70% 2-methoxyethanol and 30% acetone, with test material identity confirmed by GCMS.

Method

Ethical approval:
confirmed, but no further information available
Details on study design:
Analytical method: Air sampling: Method of IOSH Taipai, Taiwan. Urinary measurements as described in reference Shih et al (1999) Occup Env Med, 56, 460-7 - method validated by IOSH.
Exposure assessment:
measured
Details on exposure:
TYPE OF EXPOSURE: Dermal and inhalation

TYPE OF EXPOSURE MEASUREMENT: Personal sampling and urine Biomonitoring (methoxyacetic acid - MAA)

EXPOSURE LEVELS: See results

EXPOSURE PERIOD: First period Feb 1997: 5 consecutive full shifts. For second and third measurement periods (April and August 1997): one full 8 hour shift each.

DESCRIPTION / DELINEATION OF EXPOSURE GROUPS / CATEGORIES: Group of 29 exposed workers (24 male, 5 female) from the coatings department of a copper clad laminate manufacturing plant. 90 workers (including 32 non exposed heat press workers and 58 froma separate administration building) used as control group. All subjects requeste to avoid exposure to alcohol or other solvents during monitoring period.

OTHER INFORMATION: Data questionnaires used to collect personal history information.

Results and discussion

Results:
Exposure to 42ppm average levels of methoxyethanol produced significant changes to blood parameters. Many, but not all parameters showed recovery to normal levels when exposures had reduced to 2.65ppm and 0.55ppm. The study showed poor correlation between the exposed group personal monitoring air exposure values and the biological monitoring parameters which was far from linear. In particular, whilst the air exposure values for the male exposed group dropped from 41.9ppm to 0.55ppm between the start and end of the study (~70 fold) , the level of methoxyacetic acid (MAA) measured in urine only fell from 57.7 to 13.5 mg MAA/g creatinine (~4 fold). Since the control group measurements were 0.19ppm and 1.02 mg MAA/g creatinine, this does suggest that a significant element of the internal dose resulted from internal exposure, especially in the August group. This means that this study cannot be reliably used to determine the no effect level for 2-methoxyethanol exposure in humans (using haematological parameters as the measure of effect.)

Any other information on results incl. tables

Exposure parameters

 

Parameter

Control group (Feb)

February group

April group

August group

Air conc (ppm) [SD]

0.19 [0.3]

All: 35.7 [78]

Male: 41.9 [83.5]

Female 5.9 [3.6]

2.65 [1.5]

0.55 [0.73]

Minimum (ppm)

0

0.75

0.2

0.1

Maximum (ppm)

0.8

320

10

3.5

Urinary MAA (mg/gCr) [SD]

1.02 [1.25]

57.7 [31.8]

24.6 [10.6]

13.5 [10.6]

Minimum (mg/g Cr)

0

24.3

4.6

0.95

Maximum (mg/g Cr)

4.22

139

54.9

25.2

N=29 for exposed groups (24 males, 5 females), 91 for control group)

 

Haematological parameters for males (n=24)

 

Parameter

Control group (Feb)

February group

April group

August group

Haemoglobin g/l [SD]

155 [110]

137 [185]

152 [75]

155 [88]

Packed cell volume (%) [SD]

48.1 [3.22]

41.8 [6.6]

45.2 [2.2]

48.2 [2.43

Red blood cell (10E12/l) [SD]

5.47 [0.56]

4.54 [0.72]

4.93 [0.4]

5.26 [0.36]

Lymphocytes (10E9/l) [SD]

2.17 [0.47]

2.76 [0.77]

2.32 [0.75]

2.25 [0.63]

Platelets (10E9/l) [SD}

248 [59]

305 [61]

254 [57]

237 [65]

Mean corpuscular volume (fl) [SD]

88.6 [7.8]

92.6 [6.8]

92.0 [6.1]

91.8 [6.23]

Mean corpuscular haemoglobin (pg) [SD]

28.6 [3.0]

30.5 [2.27]

30.9 [2.28]

29.5 [2.2]

Mean corpuscular haemoglobin concentration (

32.2 [1.08]

32.9 [0.81]

33.5 [0.78]

32.1 [0.8]

All the values in the table above showed a statistically significant difference (p<0.05) between the control group and the February exposed groups. There was no significant differences in the levels of total white blood cells and neutrophils (values not shown here). There was no significance for trend with lymphocytes but there was with levels of total white blood cells. There was no significant differences seen between exposed and control females (although exposed group was small which would have meant weak statistical power).

 

By the April measurements, Hgb, PCV, RBC and platelet counts had returned to normal values (not statistically significantly different from controls.) There is no information in the study report to indicate if the values for  The corpuscular parameters did not appear to have recovered back to the control values. The study report indicated statistical significance for positive trend (only just for MCV) but did not indicate if the August values were still statistically significant from controls.

Applicant's summary and conclusion

Executive summary:

A study was carried out to examine the association between occupational full shift exposure and haematological effects and their reversibility before and after implementation of exposure risk reduction measures. 29 exposed and 90 none exposed workers were recruited. Whole shift personal exposures were measured and urinary levels of methoxyacetic acid where determined. Haematological parameters were assessed on blood samples taken at the end of the exposure periods (3 in a 6 month period). Exposure to 42ppm average levels of methoxyethanol produced significant changes to blood parameters. Many, but not all parameters showed recovery to normal levels when exposures had reduced to 2.65ppm and 0.55ppm. However, the study shows that the correlation between the exposed group personal monitoring air exposure values and the biological monitoring parameters was far from linear. In particular, whilst the air exposure values for the male exposed group dropped from 41.9ppm to 0.55ppm between the start and end of the study (~70 fold) , the level of methoxyacetic acid (MAA) measured in urine only fell from 57.7 to 13.5 mg MAA/g creatinine (~4 fold). Since the control group measurements were 0.19ppm and 1.02 mg MAA/g creatinine, this does suggest that a significant element of the internal dose resulted from internal exposure, especially in the August group. This means that this study cannot be reliably used to determine the no effect level for 2-methoxyethanol exposure in humans (using haematological parameters as the measure of effect.)