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Toxicological information

Specific investigations: other studies

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Administrative data

Endpoint:
hematoxicity
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Validation and evaluation of biomarkers in workers exposed to benzene in China
Author:
Qu, Q, Shore, R, Li, G, Jin, X, Chen, LC, Cohen, B,|Melikian, AA, Eastmond, D, Rappaport, S, Li, H, Rupa, D,|Waidyantha, S, Yin, S, Yan, H, Meng, M, Winnik, W, Kwok,|ESC, Li, Y, Mu, R, Xu, B, Zhang, X and Li, K|. Research Report 115, Health Effects|Institute, Boston MA.
Year:
2003
Bibliographic source:
Res Rep Health Eff Inst. 2003 Jun;(115):1-72; discussion 73-87.
Title:
No information
Author:
Qu, Q, Shore, R, Li, G, Jin, X, Chen, LC, Cohen, B,|Melikian, AA, Eastmond, D, Rappoport, SM, Yin, S, Li, H,|Waidyanatha, S, Li, Y, Mu, R, Zhang, X and Li, K. (2002)|Hematological changes among Chinese workers with a broad|range of benzene exposures. Am J Ind Med. 42, 275-285.

Materials and methods

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Any other information on results incl. tables

EXPOSURE TO BENZENE, TOLUENE AND XYLENES
Benzene exposure was calculated and presented as the current daily exposure (based on biological monitoring), a 4-wk average exposure levels (based on monitoring data and biological monitoring) and the lifetime cumulative exposure (based on job histories and historical exposure data for the factory). Daily benzene levels for the exposed subjects were in a range 0.06-122 ppm with a median of 3.2 ppm. The 4-wk mean range was 0.08-54.4 ppm, and the cumulative lifetime exposure was 6.1-623.2 ppm-years.

HAEMATOLOGICAL CHANGES
Graphical data indicate that there were significant exposure-related decreases in RBC, WBC and neutraphils (all P0.001) but no clear effect on lymphocytes. 

Regression analysis revealed significant negative associations between benzene exposure and RBC (P0.05), WBC (P0.001) and neturaphils (P0.001). In addition, after adjustment for potential confounders (sex, age, toluene, cotinine), there were also weak negative associations between benzene exposure and decreased lymphocyte (P0.01) and monocyte counts (data not reported).

Analyses were performed to examine blood cell counts at current low levels of exposure (4-wk average exposure of 0.25 ppm benzene or lower). This showed statistically significant decreases in RBC, WBC and neutraphils in the exposed group, which remained after adjustment for confounding factors. 


Comment: While this appears to be one of the key findings from this study, the underlying data were not obvious from tables and figures included in the publication. The reliability of the exposure estimates is also unclear since it is noted elsewhere (Qu et al., 2003) that changes in the low exposure workers may have been due to past cumulative exposure to benzene.

Graphical results demonstrated statistically significant decreases in RBC (P0.001), WBC (P0.001) and neutraphils (P0001) when blood cell counts were analysed relative to cumulative benzene exposure. (The authors comment that the differences RBC appeared primarily due to a difference between the exposed and unexposed population with little gradation in response to cumulative exposure, reducing confidence in the association.) 

After adjustment for possible confounders, regression analyses of blood cell parameters relative to cumulative exposure showed strong inverse associations with RBC (P0.01), WBC (P0.05), neutraphils (P0.01) and monocytes (not reported), with weaker associations for lymphocytes (P0.001) and eosinophils (not reported).

An analysis of the relative contribution of benzene exposure duration and intensity showed that RBC (P0.01; approx. 17% decrease with 18 yr or more exposure) and neutraphils (P0.001; approx. 21% decrease) were influenced by duration of exposure while RBC (P0.01; approx. 15% decrease at 40 ppm-yr and above), WBC (P0.01; 29% decrease), neutraphils (P0.01; 38% decrease) and eosinophils (not reported) were affected by average exposure concentration per year.


An exposure-response regression analysis showed that benzene exposure intensity predicted decreases in RBC, WBC, lymphocyte, neutraphil, monocyte and eosinophil counts while exposure duration showed only a weak association with neutraphils. Hence benzene exposure intensity appeared more predictive of bone marrow depression than duration of exposure.

CORRELATION BETWEEN MARKERS OF EXPOSURE AND BLOOD CELL CHANGES
Significant correlation was found between the presence of S-PMA, t,t-MA, BO-Alb and 1,4BQ-Alb in urine and decreased RBC, WBC and neutraphil counts.

Applicant's summary and conclusion

Conclusions:
Exposure-dependent decreases in red blood cell, white blood cell and neutraphil counts were reported in this study, with significant effects apparently present in subjects currently exposed to 0.25 ppm benzene or below (although confounding due to higher cumulative exposures in the past could not be excluded). Decreases in blood cell parameters correlated with the presence (but not level) of biomarkers of benzene exposure present in urine.