Oral fluid assays for the detection of heavy metal exposure

Abstract

Methods for measuring the concentration of heavy metals such as aluminum, antimony, arsenic, barium, beryllium, cadmium, chromium, cobalt, copper, lead, manganese, molybdenum, nickel, selenium, silver, strontium, thallium, uranium, vanadium, zinc, or mixtures thereof in oral fluid are provided. The concentration of heavy metals in oral fluid can be accurately correlated with the concentration of heavy metal in the blood serum. The methods are useful for, among other things, diagnosis and monitoring of heavy metal exposure.

1 . A method of assaying a subject for heavy metal exposure, comprising providing a sample of oral fluid from a subject, said sample obtained by contacting the gumline of the subject, and measuring the concentration of said heavy metal present in said sample, wherein said heavy metal comprises aluminum, antimony, arsenic, barium, beryllium, cadmium, chromium, cobalt, copper, lead, manganese, molybdenum, nickel, selenium, silver, strontium, thallium, uranium, vanadium, zinc, or mixtures thereof. 
     
     
         2 . The method of  claim 1 , wherein the subject is a human. 
     
     
         3 . The method of  claim 1 , wherein providing the sample comprises providing a swab comprising the subject's oral fluid. 
     
     
         4 . The method of  claim 3 , wherein providing the swab comprises rubbing the swab along the vestibular aspect of the mandibular gumline. 
     
     
         5 . The method of  claim 3  or  4  wherein the swab comprises a polymer of ethylene glycol and terephthalic acid. 
     
     
         6 . The method of  claim 3  further comprising digesting the swab using acid or microwave radiation. 
     
     
         7 . The method of  claim 1 , wherein said measuring step utilizes atomic absorption spectrometry, atomic emission spectroscopy, electrospray ionization tandem mass spectrometry, high performance liquid chromatography tandem mass spectrometry, inductively coupled plasma optical emission spectroscopy, and capillary zone electrophoresis mass spectrometry. 
     
     
         8 . The method of  claim 1 , wherein said measuring step utilizes inductively coupled plasma mass spectrometry. 
     
     
         9 . The method of  claim 1 , wherein the heavy metal is arsenic, cadmium, or lead. 
     
     
         10 . The method of  claim 1 , wherein the heavy metal exposure is intoxication. 
     
     
         11 . The method of  claim 1 , further comprising the step of correlating the concentration of said heavy metal in said sample with the concentration of said heavy metal in said subject. 
     
     
         12 . The method of  claim 11 , wherein said correlating step comprises comparing the concentration measurement with reference values for no exposure to the heavy metal, low level of exposure to the heavy metal, moderate level of exposure to the heavy metal, or high level of exposure to the heavy metal; said measurement relative to the reference values being indicative of the level of the heavy metal in the blood of the subject. 
     
     
         13 . The method of  claim 12 , wherein said concentration of heavy metal in said sample is predictive of the amount of heavy metal in the blood of said subject with a confidence interval of greater than 90%. 
     
     
         14 . The method of  claim 13  wherein said concentration of heavy metal in said sample is predictive of the amount of heavy metal in the blood of said subject with a confidence interval of greater than 95%. 
     
     
         15 . The method of  claim 14  wherein said concentration of heavy metal in said sample is predictive of the amount of heavy metal in the blood of said subject with a confidence interval of greater than 98%. 
     
     
         16 . The method of  claim 15  wherein said concentration of heavy metal in said sample is predictive of the amount of heavy metal in the blood of said subject with a confidence interval of greater than 99%. 
     
     
         17 . A method for predicting the concentration of a heavy metal in the blood of a subject, comprising providing a sample of oral fluid from the subject, said sample obtained by contacting the gumline of said subject, determining the concentration of the heavy metal in the oral fluid, wherein the concentration of said heavy metal in the oral fluid is predictive of the concentration of said heavy metal in the blood of the subject, wherein said heavy metal comprises aluminum, antimony, arsenic, barium, beryllium, cadmium, chromium, cobalt, copper, lead, manganese, molybdenum, nickel, selenium, silver, strontium, thallium, uranium, vanadium, zinc, or mixtures thereof. 
     
     
         18 . The method of  claim 17 , wherein the subject is a human. 
     
     
         19 . The method of  claim 18 , wherein the heavy metal is arsenic, cadmium, or lead. 
     
     
         20 . The method of  claim 17 , wherein the step of providing a sample of oral fluid comprises rubbing a swab along the vestibular aspect of the subject's mandibular gumline. 
     
     
         21 . The method of  claim 20 , wherein the swab comprises a polymer of ethylene glycol and terephthalic acid. 
     
     
         22 . The method of  claim 18  further comprising digesting the swab using acid or microwave radiation. 
     
     
         23 . The method of  claim 17 , wherein said measuring step utilizes atomic absorption spectrometry, atomic emission spectroscopy, electrospray ionization tandem mass spectrometry, high performance liquid chromatography tandem mass spectrometry, inductively coupled plasma optical emission spectroscopy, and capillary zone electrophoresis mass spectrometry. 
     
     
         24 . The method of  claim 17 , wherein the step of determining comprises the use of inductively coupled plasma mass spectrometry. 
     
     
         25 . A system for providing a quantitative assessment of heavy metal intoxication, said system comprising a sample of oral fluid from a subject obtained by contacting the gumline of a patient and means for measuring the amount of said heavy metal in said sample, wherein said heavy metal comprises aluminum, antimony, arsenic, barium, beryllium, cadmium, chromium, cobalt, copper, lead, manganese, molybdenum, nickel, selenium, silver, strontium, thallium, uranium, vanadium, zinc, or mixtures thereof. 
     
     
         26 . The system of  claim 25  wherein said means for measuring the amount of said heavy metal in said sample comprises atomic absorption spectrometry, atomic emission spectroscopy, electrospray ionization tandem mass spectrometry, high performance liquid chromatography tandem mass spectrometry, inductively coupled plasma optical emission spectroscopy, and capillary zone electrophoresis mass spectrometry. 
     
     
         27 . The system of  claim 25 , wherein said heavy metal is arsenic, cadmium, or lead. 
     
     
         28 . The system of  claim 25 , wherein said sample comprises oral fluid on a swab. 
     
     
         29 . The system of  claim 28 , wherein said swab comprises a polymer of ethylene glycol and terephthalic acid.