Mercury

Exposure related observations in humans: other data

Administrative data

Endpoint:

exposure-related observations in humans: other data

Type of information:

other: human study

Adequacy of study:

key study

Reliability:

other: reliable study report; not rated acc. to Klimish

Rationale for reliability incl. deficiencies:

other: Study identified as one of three key studies by EuroChlor2009. Well documented study

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference 1

Reference Type:

review article or handbook

Title:

Metallic mercury (Hg) - The biological affects of long-time low to moderate exposures.

Author:

Efskind, J.

Year:

2009

Bibliographic source:

Euro Chlor Science Dossier 13

Reference 2

Reference Type:

publication

Title:

Renal and immunologic markers for chlor-alkali workers with low exposure to mercury vapor.

Author:

Ellingsen, D.G.; et al.

Year:

2000

Bibliographic source:

Scand. J. Work. Environ. Health. Oct. 26(5): 427-35.

Materials and methods

Type of study / information:

The aim of the study was to investigate renal function and immunologic markers among chloralkali workers with long-term low exposure to mercury vapour. 47 chloralkali workers exposed to mercury vapour for an average of 13.3 (2.8-34.5) years were compared with 47 referents matched for age in a cross sectional study of thyroid function.

Endpoint addressed:

repeated dose toxicity: inhalation

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

The aim of the study was to investigate renal function and immunologic markers among chloralkali workers with long-term low exposure to mercury vapour. 47 chloralkali workers exposed to mercury vapour for an average of 13.3 (2.8-34.5) years were compared with 47 referents matched for age in a cross sectional study of thyroid function.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

439-97-6

IUPAC Name:

439-97-6

Constituent 2

Reference substance name:

Mercury

EC Number:

231-106-7

EC Name:

Mercury

Cas Number:

7439-97-6

Molecular formula:

Hg

IUPAC Name:

mercury

Details on test material:

- Name of test material (as cited in study report): mercury vapour
- Molecular formula (if other than submission substance): Hg
- Substance type: no data
- Physical state: gaseous
No further information given.

Method

Ethical approval:

confirmed and informed consent free of coercion received

Details on study design:

Subjects:
- Eligible for inclusion: men, exposed to mercury vapour for at least 1 year in a contaminated area of the plant under study (n=67).
- Worker fulfilling the criteria for target population: n=51 were offered voluntary medical examination and they received written information.
- Reference group: men employed by the same company at the same industrial complex, working on clellulose bleaching, drying, packing facilities and lignine drying and producing, and who had no known current or past occupational exposure to mercury.
- The reference subjects were matched to the exposed subjects for age (+/- 3 years) in pairs.
- Examination response rate of the 51 exposed workers was 100 %; reponse rate of 56 references was 91.1 %.
- Exlusion criteria included alcohol abuse, major head injuries, metabolic disorders and major psychiatric, neurologic or other diseases causing severe diability.
- 4 exposed workers and 2 references were excluded due to medical conditions.
- Thus, the report describes the results of 47 exposed workers and 47 references.
- Workers had been routinely monitored by measurements of the U-Hg since opening of the plant in 1949 (since 1960, cold vapour AAS was used).

Laboratory measurements:
- First-voided morning urine was collected from the day before and the day of examination.
- Trace elements were measured in the second sample.
- Blood specimens were obtained from the cubital vein.
- Heparinized whole blood was collected for measurements of trace elements.

Renal markers:
- Serum and urine were stored; all measurements were carried out on day 60 after the sampling.
- Determinations in urine: U-AAP, U-β2, U-NAG, U-ALP, U-Alb, U-GAG, U-Kal (renal markers); optical density, creatine, albumin.
- Determinations in serum: ANA, anti-GBM, anti-MPO, anti-PR3, IgE, creatine, β2-microglobulin.
- Urinary mercury and total mercury in whole blood: U-Hg and B-Hg-total were measured by cold-vapour AAS.
- Inorganic mercury in whole blood: B-Hg-inorg was measured by cold-vapour AAS.
- Cadmium and selenium in whole blood and urine: B-Cd and B-Se as well as U-Cd and U-Se were measure by electrothermal atomic absorption spectrometry

Accuracy and precision:
- Assessed with reference material for human whole blood and urine.
- Day to day variations of U-Hg, B-Hg and B-Hg-inorg were typically 1.2 %, 5 %, and 8 %, resp.; the results agreed well with the recommended values; a different method was used for B-Hg-inorg as no reference material was available.
- Average concentration of B-Cd and U-Cd agreed with the recommend values; the day-to-day variation was 10 % and 13 %, resp.
- B-Se concentration agreed with the recommend values; for U-Se concentration no recommended value was available

Statistics:
The mean concentrations of urinary markers of renal toxicity of the two consecutive days are presented. Several of the measured variables had skewed distributions. They were log-transformed if the skewness exceeded 2.0 or if the distributions to be compared had different variances (Levene’s test). An analysis of variance was used for the group comparisons. If more than 2 groups were compared, the least square difference was calculated post hoc to separate the groups that differed. General factorial analysis was used to control for the covariates. Association between effect variables, exposure measures, and potential confounders were assessed with a multiple linear regression analysis (backward procedure). The exposure measures (current B-Hg-inorg, current U-Hg, cum U-Hg, and cum U-Hg/yr) were entered separately into the models to avoid potential problems of collinearity. The level of statistical significance was set at P<0.05 (2-tailed). The statistical package SPSS, version 8.0, was used.

Exposure assessment:

measured

Details on exposure:

TYPE OF EXPOSURE: workers were exposed to low concentrations of mercury vapour on their workplace for more than one year

TYPE OF EXPOSURE MEASUREMENT:
- the workers had been routinely monitored by measurements of the U-Hg since opening of the plant in 1949 (since 1960, cold vapour AAS was used)
- the results from about 2200 measurements of U-Hg were identified among the 47 included exposed workers (mean 2.9 measurements/worker annually)
- U-Hg was measure without correction for urinary creatine until 1982; thus the mean of the individual urinary creatine concentrations measured in 1982 and 1983 was used to correct the concentrations measured prior
- a Cum U-Hg was calculated based on the worker’s mean U-Hg for each quarter of the year; and based on thses quarterly measurements, a mean U-Hg for each year of exposure was calculated, and all years of exposure were added to yield the Cum U-Hg; furthermore, an index of the mean intensity of exposure (Cum U-Hg/yr) was calculated by dividing Cum U-Hg by years of exposure.
- the concentrations of U-Hg and inorganic mercury in whole blood (B-Hg-inorg) at the time of examination were indices used for current exposure

EXPOSURE LEVELS: Hg concentration was only determined in urine and blood; urine-Hg was 1.1 - 16.8 nmol/mmolcreatine (mean 5.9) for exposed workers and 0.2 - 5.0 nmol/mmol Cr (mean 1.3) for referents;whole blood-Hg was 10.0 - 108 nmol/L (mean 43.5) for exposed workers and 8.0 - 36.0 nmol/L (mean 18.5) for referents; inorganic mercury in whole blood was 2.5- 65.0 nmol/L (mean 20.7) for exposed workers and 2.5 - 18.0 nmol/L (mean 5.7) for referents; Cum U-Hg was 14.5 - 490.6 nmol/mmol Cr (mean 123.2) for exposed workers; Cum U-Hg/yr was 4.0 - 19.6 nmol/mmol Cr (mean 9.0) for exposed workers

EXPOSURE PERIOD: 2.8 - 34.5 years at workplace (mean 13.3 years)

POSTEXPOSURE PERIOD: not applicable

DESCRIPTION / DELINEATION OF EXPOSURE GROUPS / CATEGORIES: only exposed and not exposed subjects were examined for the study, however, workers were stratified into 3 equally large groups according to the different exposure measures and compared to their corresponding age-matched referents for results assessment

Results and discussion

Results:

- Mean mercury concentrations in exposed workers were 5.9 nmol/mmol creatinine (range 1.1-16.8) vs. 1.3 nmol/mmol creatinine (range 0.2-5.0) in the reference group.
- Workers were stratified into 3 equally large groups according to the different exposure measures and compared to their corresponding age-matched referents.
- The activity of U-NAG was significantly higher in the exposed workers (mean 0.18 U/mmol Cr) compared to the reference group (mean 0.14 U/mmol Cr).
- Associations between current urinary Hg, cumulative urinary Hg, cumulative urinary Hg per year and U-NAG, anti-MPO and proteinase 3 in serum were observed.
- The activity of U-NAG and anti-MPO was increased in workers with the highest exposure as expressed by the ratio of exposed workers and their referents. The concentrations were similar for workers with low exposure levels and their referents.
- Urinary Hg was 2.7 (1.1-3.7), 4.6 (3.8-5.6) and 10.0 (5.8-16.8) nmol/mmol Cr in the low, medium and high exposure groups, respectively.
- The ratios of U-NAG were 1.06 (0.72-1.58), 1.39 (1.04-1.86) and 1.41 (1.02-1.94), respectively, and for anti-MPO 0.91 (0.72-1.15), 1.0 (0.79-1.26) and 1.44 (1.14-1.82) for the low, medium and high exposure groups, respectively.
- The highest activity of U-NAG was observed in the exposed workers with the lower Se concentrations in blood (B-Se was neagatively associated with U-NAG).
- The study indicates an effect of exposure on the kidney proximale tubule cells, possibly modified by individual Se status and an effect mediated by neutrophile granulocytes.

Applicant's summary and conclusion

Conclusions:

In conclusion, the study indicates an effect of exposure on the kidney proximale tubule cells, possibly modified by individual Se status and an effect mediated by neutrophile granulocytes.