Occupational exposure to trichloroethylene is associated with a decline in lymphocyte subsets and soluble CD27 and CD30 markers

Abstract

Occupational cohort and case-control studies suggest that trichloroethylene (TCE) exposure may be associated with non-Hodgkin lymphoma (NHL) but findings are not consistent. There is a need for mechanistic studies to evaluate the biologic plausibility of this association. We carried out a cross-sectional molecular epidemiology study of 80 healthy workers that used TCE and 96 comparable unexposed controls in Guangdong, China. Personal exposure measurements were taken over a three-week period before blood collection. Ninety-six percent of workers were exposed to TCE below the current US Occupational Safety and Health Administration Permissible Exposure Limit (100 p.p.m. 8 h time-weighted average), with a mean (SD) of 22.2 (36.0) p.p.m. The total lymphocyte count and each of the major lymphocyte subsets including CD4+ T cells, CD8+ T cells, natural killer (NK) cells and B cells were significantly decreased among the TCE-exposed workers compared with controls (P < 0.05), with evidence of a dose-dependent decline. Further, there was a striking 61% decline in sCD27 plasma level and a 34% decline in sCD30 plasma level among TCE-exposed workers compared with controls. This is the first report that TCE exposure under the current Occupational Safety and Health Administration workplace standard is associated with a decline in all major lymphocyte subsets and sCD27 and sCD30, which play an important role in regulating cellular activity in subsets of T, B and NK cells and are associated with lymphocyte activation. Given that altered immunity is an established risk factor for NHL, these results add to the biologic plausibility that TCE is a possible lymphomagen.

Fig. 1.

(a) Peripheral blood cell counts in relation to TCE exposure level. P_trend using category of TCE levels (controls, <12 p.p.m. and ≥12 p.p.m.) as a continuous variable. The median TCE concentration of all exposed subjects was 12 p.p.m. Differences in cell counts were tested by linear regression analysis of ln-transformed end point, adjusting for relevant covariates [white blood cell (WBC): adjusted for age, sex, smoking status and body mass index; granulocytes: adjusted for age, sex and body mass index; Monocytes: adjusted for age, sex and smoking status; lymphocyte: adjusted for age and sex]. (b) Lymphocyte subsets cell counts in relation to TCE exposure level. Differences in cell counts were tested by linear regression analysis of ln-transformed end point, adjusting for relevant covariates [CD4⁺, CD8⁺ and NK T cells: adjusted for age and sex, three subjects (two controls and one exposed) were deleted due to inconsistent cell counts using complete blood count data versus flow cytometry to calculate % lymphocytes; B cell: adjusted for age, sex and smoking status]. The P values are indicated as: **P < 0.01; ***P < 0.001 and ****P < 0.0001.

Fig. 2.

Soluble CD27 and CD30 in relation to TCE exposure level. P_trend using category of TCE levels (controls, <12 p.p.m. and ≥12 p.p.m.) as a continuous variable. The median TCE concentration of all exposed subjects was 12 p.p.m. Differences in sCD27 and sCD30 were tested by linear regression analysis of ln-transformed end point, adjusting for age, sex and infection. For sCD27, results available for 38 subjects exposed to <12 p.p.m. TCE. The P values are indicated as: **P < 0.01; and ****P < 0.0001.