Risk Assessment Of Nerve Conduction Velocity Change In Workers Exposure To Lead

Lead is one of metal element which has been considered as a environmental harmful pollutant concerned of WHO and ATSDR. Lead can cause toxic effects on several organs in human. Exposure to lead can cause nerve injury,kidney damage, and toxicity of hemoglobin metabolism. At lower doses, lead has been associated with alterations in cognitive development in children. Because of difference of nutrition, lifestyles, especially the genetic background, workers in the same workplace show different susceptibility to lead toxicity and poisoning. Better understanding of genetic factors that influence susceptibility to lead-induced toxic effects is very important for prevention and protection against lead toxicity in occupationally workers'health.The purpose of our study are:(1) To investigate the effects of occupational lead exposure on nerve conduction velocity changes using the method of epidemiological investigation and the dose-response relationship between lead exposure and the toxicity effeects on nerve and blood system using the method of benchmark dose (BMD). (2) To analysis the relationship between exposure biomarkers (BPb, SPb, UPb) and effective biomarkers (nerve conducting velocity and hemoglobin, ZPP, urinaryδ-ALA). (3) To investigate the BMD value and BMDL value of blood lead reflecting nerve conducting velocity and hemoglobin, ZPP, urinaryδ-ALA in workers exposure to lead. (4) To examine a possible relationship between lead and its effects on nerve conduction velocity and the relationship betweenδ-Aminolevulinic Acid Dehydratase (ALAD)gene polymorphism, vitamin receptor gene polymorphism and lead toxicity on nerve and blood system.There are 221 workers were selected from lead exposure factories, including 158 males and 63 females, with average length of work 1.75years (1 month to 15 years).The monitoring data shows:the average concentration of air lead is 0.70 mg/m3, seven times more than TWA of Chinese national standard. The control group included 91 subjects (male 65, female 26),and the location of control factory is 2 km far from the battery factory. The living style, social and economic condition, and constitiue of control factory are similar with the lead exposur factory. The information of workers was collected with questionnaires.We used the portable electromyography apparatus to meassure the nerve conduction velocity of upper limbs and lower limbs in each subject of study population. Blood lead, urinary lead and serum lead were measured as exposure biomarkers. Motor median nerve conduction velocity,sense median nerve conduction velocity, motor ulnar nerve conduction velocity,sense ulnar nerve conduction velocity, motor superficial peroneal nerve conduction velocity, and sense superficial peroneal nerve conduction velocity,and zpp, hemoglobin, urinaryδ-ALA were also measured as effect biomarkers. We estimated benchmark dose(BMD) and the lower confidence limit of the benchmark dose (BMDL)for the adverse effects of nerve and hemoglobin metabolism. We also measured the ALAD and VDR genotype for each subject.We calculate the external dosage of lead exposure:The lead dust concentration varibrate largely. The highest lead dust concentration in workshop is 3.08 mg/m3 and the lead dust concentration in 2006 dreases with the upper concentration 0.75 mg/m3. The lead dust concentration in 2007 raised with the upper concentration 0.75 mg/m3.52 locations were monitored from 2005 to 2007,50 locations exceeding the national standard. The external dosage estimination shows:with the manufacturing technique in different workshop varying, there are different average lead dust concentration in different workshops. The external dosage of workers increase with exposure hours and work length.Effects of lead on nerve system:It was showed that BPb, SPb, and UPb levels in the exposure group were significantly higher than those in the control group. The values of nerve conduction velocity in the exposure group were lower than those in control group. We define 95% upper limits of each index of control group as the abnormal value. The abnomal rates of exposure group were significantly higher in control group. After dividing the participants into several groups according to SPb, UPb and BPb levels, respectively, sense nerve conduction velocity significantly decreased when BPb was higher than 200μg/L, sense nerve conduction velocity significantly decreased when UPb was higher than 10μg/gCr. Sense nerve conduction velocity significantly decreased when SPb was higher than 5μg/L. The prevalence of abnormity of nerve conduction velocity were significantly increasing following the increase of BPb,UPb and SPb levels. After benchmark dose calculatin for nerve conduction velocity, we found sense ulnar nerve conduction velocity and sense median nerve conduction velocity are small values.The BMDLs of blood lead calculated basing on median nerve conduction velocity, ulnar nerve conduction velocity, and superficial peroneal nerve conduction velocity were 457.6μg/L,333.0μg/L,468.4μg/L respectively; The BMDLs of urine lead calculated basing on median nerve conduction velocity, ulnar nerve conduction velocity, and superficial peroneal nerve conduction velocity were 14.1μg/gCr,9.2μg/gCr,13.6μg/gCr respectively. The BMDLs of serum lead calculated basing on median nerve conduction velocity, ulnar nerve conduction velocity, and superficial peroneal nerve conduction velocity were 7.87μg/L,5.43μg/L,8.51μg/L respectively. Ulnar nerve conduction velocity can be used as highly sensitive biomarkers to screen the high risk population of lead exposureLaboratory examination were adopted for measurement of other biological indices such as blood lead, blood zinc protoporphyrin (ZPP), urinaryδ-ALA and hemoglobin content in lead exposed group and control group. Sense nerve conducting velocity decreases significantly than motor nerve conducting velocity. The data indicates that decreasing of sensory nerve conducting velocity of lead contact worker was sensitive than that of motor nerve conducting velocity. The lowest BMDL of blood lead value reflecting nerve conducting velocity is of ulnar nerve sensory conducting velocity, which is 332.3μg/L. The BMDL of blood lead value reflecting ZPP, hemoglobin and Urinaryδ-ALA are separately 223.8μg/L,263.4μg/L,377.5μg/L. Generally, this study indicates lead blood can be used as the early screening index of nerve conducting injury. And the phenomenon of nerve conducting velocity decreasing is later than the change of ZPP and hemoglobin in lead exposed workers. When blood lead levels arrivals at 300μg/L, ZPP could be used to estimated the changes in the recent lead exposure level.Our researches have implicated that the polymorphism ofδ-Aminolevulinic Acid Dehydratase (ALAD)gene is associated with lead body burden and susceptibility of lead toxixity on humans. Given the ALAD polymorphism found in humans and the knowledge that the enzyme is sensitive to inhibition by lead. Study on ALAD gene polymorphism:It has been proved that the susceptibility to lead toxicicy is related toδ-Aminolevulinic Acid Dehydratase gene polymorphism. Polymerase chain reaction-restriction fragmant lengthδ-ALAD genotype. The results revealed that the frequencies of ALAD1-1 and ALAD1-2 genotype were 92.8% and 8.2% respectively. No ALAD1-2 homozygote was found. The frequencies of alleles of ALAD1 and ALAD2 were 94.2% and 5.8%,respectively. In the exposure group, Blood lead with ALAD1-2 genotype were obviously higher than those of ALAD1-1 genotype.While in the control group, there was no remarkable difference between the two genotypes in blood lead, urinary lead and the indexes of zpp and hemoglobin.Also, the vitamin receptor gene is associated with lead body burden and susceptibility of lead toxicity on humans. Study on Bsm I gene polymorphism:The results revealed that the frequencies of Bsm-BB and Bsm-Bb genotype were 15.64% and 84.36% respectively. No Bsm-bb homozygote was found. The frequencies of alleles of Bsm-B and Bsm-b were 7.82% and 92.08%,respectively. In the exposure group, Blood lead with Bsm-BB genotype were obviously higher than those of Bsm-Bb genotype.While in the control group, there was no remarkable difference between the two genotypes in blood lead, urinary lead and the indices of zpp and hemoglobin.In conclusion, the absorption of lead in workers can be roughly calculated through measuring the external dosage of lead exposure. The differences between short-term higher lead concentration exposure and long-term lower lead concentration exposure cannot be easily figured out. The correlation between the external dosage and inernal dosage is weak. The correlation among blood lead, urinary lead and serum lead vary from 0.528 to 0.619. the highest correlation is between blood lead and serum lead, which is 0.620. When we evaluate different effect indexes, we should select different exposure biomarkers.The sense ulnar conduction velocity decreases when the blood lead value reachs 333.0μg/L, serum lead value reachs 5.43μg/L, and urinary lead value reachs 9.19 u g/gCr. Sense ulnar nerve conduction velocity is the most sensitive effect index. The phenomenon of nerve conducting velocity decreasing is later than the change of ZPP and hemoglobin in lead exposed workers.ALAD1-2 and Bsm-Bb gene is susceptible to lead toxicity. under the same occupational lead exposure, ALAD1-2 and Bsm-BB gene can increase the workers' lead burden, also may increase potential risk of nerve conduction and blood metabolism.