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Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
not specified
other: not rated acc. to Klimisch
Rationale for reliability incl. deficiencies:
other: Any kind of reliability rating is not considered to be applicable, since the study is not conducted/reported according to a standardised guideline.

Data source

Reference Type:
Antimony exposure and speciation in human biomarkers near an active mining area in Hunan, China
Ye, L. et al.
Bibliographic source:
Science of the Total Environment 640 - 641: 1 - 8.

Materials and methods

Study type:
study with volunteers
Test guideline
no guideline followed
Principles of method if other than guideline:
The purpose of this study was to identify human biomarkers for antimony exposure. The study region was an active antimony mining area in Hunan, China. The dietary intake of antimony and its correlation with antimony accumulation and speciation in biomarkers were analyzed. High-performance liquid chromatography (HPLC) coupled with atomic fluorescence spectrometry (AFS) was used to analyze Sb speciation in urine and saliva samples. The Sb distribution in hair and nails was explored by micro X-ray fluorescence (μ-XRF).
GLP compliance:
not specified
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
EC Number:
EC Name:
Cas Number:
Molecular formula:
Test material form:
not specified
Details on test material:
not specified
Specific details on test material used for the study:
not specified


Type of population:
- Number of subjects exposed: 100 subjects (local residents from 20 villages; The villages lay in an active mining area containing a large antimony deposit)
- Sex: males: 54; females:46
The subjects were asked to complete a questionnaire with information such as sex, age, smoking habits, years working in mine, and residence time. Ten families were randomly selected to investigate dietary habits in the study area.
Ethical approval:
not specified
Route of exposure:
Reason of exposure:
Exposure assessment:
not specified
Details on exposure:
The study area lies in an active mining area in Hunan, China. This anthropogenic antimony pollution region covers an area of about 70 km² containing a large antimony deposit (Wang et al., 2011; Wei et al., 2015)*.

- Wang, X., He, M., Xi, J., Lu, X., 2011. Antimony distribution and mobility in rivers around the world's largest antimony mine of Xikuangshan, Hunan Province, China.
Microchem. J. 97, 4–11.
- Wei, Y., Chen, Z., Wu, F., Hou, H., Li, J., Shangguan, Y., Zhang, J., Li, F., Zeng, Q., 2015. Molecular diversity of arbuscular mycorrhizal fungi at a large-scale antimony mining area in southern China. J. Environ. Sci. (China) 29, 18–26.
Samples of drinking water (n = 83), garden vegetables (n = 168), eggs (n = 11), rice (n = 9), urine (n = 63), saliva (n = 48), nails (n=47) and hair (n=51) were collected.

Vegetables and rice samples were washed with deionized water, then crushed and dried for microwave digestion analysis. Hair and nail samples were washed by deionized water-methanol-deionized water, and then dried for microwave digestion (Cui et al., 2013)*. The digestion of solid samples was completed with a microwave digestion system (MARS, CEM Corporation, U.S.).
For antimony speciation analysis in liquid samples, the urine was centrifuged, and the supernatant was filtered through a 0.22 μm membrane. Saliva was vortexed and diluted with deionized water. The diluted saliva samples were ultrasonicated and then centrifuged, and finally the supernatant was filtered (Lew et al., 2010)*.
The total dissolved antimony was detected using an atomic fluorescence spectrometer (AFS-8800 spectrometer). Online hydride generation was achieved by reacting with 2% wt. KBH4 and 7% wt. HCl. The hydride was atomized in a hydrogen flame and the fluorescence signal was recorded. For antimony speciation analysis, Sb(III), Sb(V) and TMSb in urine and saliva samples were determined using HPLC-AFS (Vinas et al., 2006; Wang et al., 2018)*. An anion exchange column was used (PRP-X100, 4.1 × 250 mm, 10 μm; Hamilton) to separate different Sb species.

Standard reference materials (citrus leaf, GBW10020; hair, GBW09101b) were used to verify the microwave digestion analysis. For quality control, selected samples were digested and analyzed in triplicate. The standard recovery rate was in the range of 90%–108%.

Nail and hair samples were analyzed using μ-XRF at beamline 15 U. Nail and hair samples were fixed on the specimen holders without any chemical treatment. The μ-XRF mapping of Sb distribution was collected at 12 keV. The beam was focused to measure a spot size of 3.5 × 2 μm² by a Kirkpatrick–Baez (KB) mirror system. Dwell-time per pixel was adjusted to 1.0 s and the step size was 5 μm (Ye et al., 2017)*.

Antimony impact on the residents in this study was estimated using a widely used model derived by the USEPA (Cui et al., 2013)*. The Sb intake from water and food was calculated using the following equation: ADD = Sb x IR x EF x ED/(1000 x AT x BW)
where ADD is the average daily dose (mg/kg bw/day); Sb is the Sb concentration (μg/L in drinking water; μg/g in vegetables and rice based on dry weight); IR is the ingestion rate (drinking water: 1.8 L/d) (Schmitt et al., 2005)*; various vegetables and rice: g/d); EF is the exposure frequency (drinking water: 365 d/y; foods: values (d/y) calculated from the questionnaire); ED is the exposure duration (y) from the questionnaire; AT is the average life expectancy (25,550 day) (Cui et al., 2013)*; and BW is the body weight (male: 61.0 kg; female: 53.2 kg) (Cui et al., 2013)*.

The R code (version 3.2.5) was used to perform the statistical analysis. Spearman's rho was used for correlating variables and Sb concentrations in urine, saliva, nails and hair. Variables included ADD, age, sex, exposure duration (ED), distance between residence and their nearest mine factories (distance), number of cigarettes per day (smoke), years working in the mine (work), and ADD contributed from drinking water (W-ADD) and food (F-ADD).
The general linear model was used to assess the relationship between Sb contents in biomarkers and independent variables. Various independent variables included in the linear regression model were age, sex, ED, Sb contents in water, ADD, distance, smoke and work. Among them, only sex was used as a categorical variable. Interaction terms (A × B) and quadratic terms (A2) were also considered in the model. The effect of each independent variable was estimated using β coefficient.
Any variable with a significance level of 0.10 was retained in the statistical model, while a variable was removed from the model if the significance level was higher than 0.10. All possible combinations of linear regression model were compared using Akaike Information Criterion (AIC), where the model with the smallest AIC was selected as the best-fit model. In addition, the goodness-of-fit was evaluated using the residual analysis.

- Cui, J.L., Shi, J.B., Jiang, G.B., Jing, C.Y., 2013. Arsenic levels and speciation from ingestion exposures to biomarkers in Shanxi, China: implications for human health. Environ. Sci. Technol. 47, 5419–5424.
- Lew, K., Acker, J.P., Gabos, S., Le, X.C., 2010. Biomonitoring of arsenic in urine and saliva of children playing on playgrounds constructed from chromated copper arsenatetreated wood. Environ. Sci. Technol. 44, 3986–3991.
- Vinas, P., Lopez-Garcia, I., Merino-Merono, B., Hernandez-Cordoba, M., 2006. Liquid chromatography-hydride generation-atomic fluorescence spectrometry hybridation for antimony speciation in environmental samples. Talanta 68, 1401–1405.
- Wang, L., Ye, L., Yu, Y., Jing, C., 2018. Antimony redox biotransformation in the subsurface: effect of indigenous Sb(V) respiring microbiota. Environ. Sci. Technol.
52, 1200–1207.
- Ye, L., Liu, W., Shi, Q., Jing, C., 2017. Arsenic mobilization in spent nZVI waste residue: effect of Pantoea sp IMH. Environ. Pollut. 230, 1081–1089.
- Schmitt, M.T., Schreinemachers, D., Wu, K., Ning, Z., Zhao, B., Le, X.C., Mumford, J.L., 2005. Human nails as a biomarker of arsenic exposure from well water in Inner Mongolia: comparing atomic fluorescence spectrometry and neutron activation analysis. Biomarkers 10, 95–104.
Medical treatment:
not applicable

Results and discussion

Clinical signs:
not specified
Results of examinations:
An geometric average Sb concentration of 13.4 μg/L (ND-522 μg/L) was found in drinking water, with 70% of samples exceeding the WHO's guideline of 6 μg/L and 71% above the Chinese national standard of 5 μg/L (Yan et al., 2017)*. Sb(V) was the predominant species in drinking water.
Sb concentrations ranging from ND to 85 μg/g with a geometric mean of 1.9 μg/g were detected in the edible parts of the food samples, with 80% exceeding the European standard of 20 μg/kg. Sb contents in foods (ND-85 μg/g) in this area were nearly eight times higher than those in other places in China and worldwide (ND-10.8 μg/g) (Fu et al., 2016)*. The foods in 13 categories exhibited different Sb accumulation capacities. Spinach (mean=18.3 μg/g) had the highest Sb content among vegetables (mean=0.39–6.22 μg/g).

By summing ADD from drinking water and foods, the residents consumed a geometric mean total ADD of 0.6 μg/kg bw/day (range from 0.005 to 11.7 μg/kg bw/day), about 57% of ADD values exceeding the RfD (0.4 μg/kg bw) (USEPA, 1991)*.
Water contributed 85%–100% of total ADD, and a significant positive correlation was found between total ADD and water Sb concentrations (rs= 0.974, p < 0.01). Sb mine activities are the most important sources of Sb pollution in water, as evidenced by the significant negative correlation between distance and water Sb concentrations (rs = −0.459, p < 0.01). Accordingly, there is also a significant negative correlation between total ADD and the distance from Sb mining regions (rs = −0.412, p < 0.01).

The geometric mean of total dissolved urinary Sb concentration in residents was 27.6 μg/L (N.D.-459 μg/L). The reference Sb level in urine is 0.2 μg/L (Hoet et al., 2013)*, ranging from 0 to 0.35 μg/L in human without Sb exposure (Nisse et al., 2017)*. Approximate 95% of analyzed urine samples exceeded 0.35 μg/L of Sb. Notably, two outliers in were observed for a man and a woman. The woman drinks about 300 μg/L Sb in water,which led to 218 μg/L urinary Sb. The man has a serious kidney disease and a high urinary Sb concentration (459 μg/L).
The geometric mean of total dissolved salivary Sb concentration in residents was 0.51 μg/L (N.D.-67 μg/L). Approximately 44% of the analyzed saliva samples exceeded the reference salivary Sb level (1.8 μg/L) (Filella et al., 2013)*. Unexpectedly, there was no correlation between urinary/salivary Sb concentrations and ADD (p > 0.05).
The Sb content ranged from N.D. to 41.8 μg/g in hair and from N.D. to 69 μg/g in nails.
Approximately 82% of hair and 83% of nail samples exceeded the reported reference levels of 0.026 μg/g in hair and 0.024 μg/g in nails (Carneiro et al., 2002; Filella et al., 2012; Vance et al., 1988)*. Sb concentrations in hair were significantly correlated with ADD (rs = 0.32, p < 0.05). The Sb content in hair was correlated with that in nails (rs = 0.335, p > 0.05), but no correlation was found between ADD and Sb concentrations in nails (p > 0.05).

To further assess the contributions of various factors to Sb accumulation in biomarkers, multivariate linear regression was used to analyze the association between Sb accumulation in biomarkers and potential confounding variables. The analysis with multiple linear regression showed that interactions (environment-personal characteristics) between pairs of independent variables (distance/ADD and age/smoke/work) explained most of the Sb levels in biomarkers. The interaction terms explained 46.0% of the urinary Sb levels, 49.6% of the salivary Sb levels, 53.8% of the Sb concentrations in hair, and 52.6% of the Sb concentrations in nails.

TMSb was the major Sb species in urine (46%–100%) with a mean concentration of 31 μg/L, followed by Sb(V) (8.1 μg/L) and Sb(III) (0.1 μg/L).
TMSb was the main Sb species in saliva (74%–100%) with an average of 5.3 μg/L, followed by Sb(V) (0.2 μg/L), and Sb(III) (N.D.).

Sb distribution in the long-term biomarkers was studied using μ-XRF. The results showed that the Sb distribution is correlated with other metal(loid)s in nail and hair samples, except for As in the hair sample. The distribution of As and Sb in nails and hairwas remarkably different. Arsenic was distributed over large expanses and concentrated in the root area of nails and hair, whereas Sb was distributed in discrete spots.

Please also refer to in the field "Attached background material" below.

- Yan, L., Song, J., Chan, T., Jing, C., 2017. Insights into antimony adsorption on {001} TiO2: XAFS and DFT study. Environ. Sci. Technol. 51, 6335–6341.
- Fu, Z., Wu, F., Mo, C., Deng, Q., Meng, W., Giesy, J.P., 2016. Comparison of arsenic and antimony biogeochemical behavior in water, soil and tailings from Xikuangshan, China. Sci. Total Environ. 539, 97–104.
- Hoet, P., Jacquerye, C., Deumer, G., Lison, D., Haufroid, V., 2013. Reference values and upper reference limits for 26 trace elements in the urine of adults living in Belgium. Clin. Chem. Lab. Med. 51, 839–849.
- Nisse, C., Tagne-Fotso, R., Howsam, M., Richeval, C., Labat, L., Leroyer, A., 2017. Blood and urinary levels of metals and metalloids in the general adult population of Northern France: the IMEPOGE study, 2008–2010. Int. J. Hyg. Environ. Health 220, 341–363.
- Filella, M., Belzile, N., Chen, Y.-W., 2012. Human exposure to antimony. II. Contents in some human tissues often used in biomonitoring (hair, nails, teeth). Crit. Rev. Environ.
Sci. Technol. 42, 1058–1115.
- Filella, M., Belzile, N., Chen, Y.-W., 2013. Human exposure to antimony. Iii. Contents in some human excreted biofluids (urine, milk, saliva). Crit. Rev. Environ. Sci. Technol.
43, 162–214.
- Carneiro, M., da Silveira, C.L.P., Miekeley, N., Fortes, L.M.D., 2002. Reference intervals for minor and trace elements in human hair for the population of Rio de Janeiro city,
Brazil. Quim. Nova 25, 37–45.
- Vance, D.E., Ehmann, W.D., Markesbery, W.R., 1988. Trace-element content in fingernails and hair of a nonindustrialized United States control population. Biol. Trace Elem. Res. 17, 109–121.
- USEPA, 1991. Antimony (CASRN 7440-36-0). Integrated Risk Information System.
Effectivity of medical treatment:
not applicable
Outcome of incidence:
not specified

Applicant's summary and conclusion

The association between Sb dietary exposure and human noninvasive biomarkers was explored. The average daily dose (ADD) (1.8 × 10E−6 to 11.7 μg/kg bw/day) was up to thirty times higher than the oral reference dose (0.4 μg/kg bw/day), which led to high Sb content in the biomarkers. However, ADDwas not the dominant factor for Sb accumulation in biomarkers according to the correlation analysis. Hair is the best non-invasive biomarker as evidenced by its significant correlation (p = 0.02) with ADD. No such correlation with ADD was found for urine (p = 0.05), saliva (p = 0.52) or nails (p = 0.85). Furthermore, the analysiswithmultiple linear regression showed that interactions (environment-personal characteristics) between pairs of independent variables (distance/ADD and age/smoke/work) explained most of the Sb levels in biomarkers. Methylated Sb was the main species in urine and saliva, as a result of the methylation process
in the human body.