Evaluation and analysis of exposure levels of di(2-ethylhexyl) phthalate from blood bags.

BACKGROUND: The US FDA and The Ministry of Health, Labor and Welfare of Japan have indicated that the risk assessment of di(2-ethylhexyl) phthalate (DEHP) released from polyvinyl chloride (PVC) medical devices requires immediate attention. In particular, the analysis of the exposure to DEHP from blood bags is very important for medical treatment. However, human exposure to DEHP via blood transfusion remains poorly understood. We evaluated DEHP and mono(2-ethylhexyl) phthalate (MEHP) levels, migration patterns, and metabolism in blood products for the detailed assessment of exposure to DEHP. METHODS: A method that is based on column-switching liquid chromatography-electrospray mass spectrometry (LC-MS) coupled with on-line extraction was used for the direct analysis of DEHP and MEHP in the blood products. From the Japanese Red Cross Society, 78 blood products (red blood cell concentrate: n=18, irradiated red blood cell concentrate: n=18, whole blood: n=18, blood platelet: n=18, and frozen plasma: n=6) were sampled in January 2003 for use in this study. RESULTS: The detection levels of DEHP and MEHP ranged from 1.8 to 83.2 microg/ml and from 0.1 to 9.7 microg/ml, respectively. The levels of MEHP and DEHP in the blood products were increased with increasing storage time. In addition, whole blood products in PVC bags had the highest DEHP levels compared to the other blood products. Our results indicate that the maximum level of human exposure to DEHP released from blood bags is 0.7 mg/kg weight/time. CONCLUSION: This first quantitative evidence may be useful for the risk assessment of DEHP released from blood bags.

Sex- and age-specific carriers of hepatitis B and C viruses in Japan estimated by the prevalence in the 3,485,648 first-time blood donors during 1995-2000.

OBJECTIVE: Carriers of hepatitis B virus (HBV) and hepatitis C virus (HCV) in Japan were estimated on a national basis. METHODS: Sera from the first-time blood donors aged 16-64 years in eight jurisdictions of the Japanese Red Cross Blood Center during 1995-2000 were tested for hepatitis B surface antigen (HBsAg) and antibody to HCV (anti-HCV). Viremia with HCV was estimated to be present in 70% of donors with anti-HCV. RESULTS: HBsAg was detected in 22,018 of 3,485,648 (0.63%) blood donors including 12,990 of 1,780,149 (0.73%) men and 9,028 of 1,705,499 (0.53%) women, and anti-HCV in 17,010 (0.49%) including 8,504 (0.48%) men and 8,506 (0.50%) women. Multiplying the carrier rate by the population registered in the Census 2000, the total HBV carriers aged 15-65 years were estimated at 967,753 (95% confidence interval 806,760-1,128,745), of whom 571,210 (479,267-663,152) were men and 396,543 (327,494-465,593) were women. Likewise, the total HCV carriers were estimated at 884,954 (95% confidence interval 725,082-1,044,826), of whom 464,363 (377,927-550,799) were men and 420,591 (347,156-494,027) were women. CONCLUSION: Estimated numbers of HBV and HCV carriers would help plan to prevent the development of hepatocellular carcinoma in Japan.

Titration of hepatitis C virus in chimpanzees for determining the copy number required for transmission.

OBJECTIVE: To determine the copy number of hepatitis C virus (HCV) RNA, determined by nucleic acid amplification test (NAT) for screening blood units in Japan, that can transmit infection to chimpanzees. METHODS: Fresh-frozen plasma with markers of HCV infection, as well as inocula pedigreed from 1 of them, were evaluated for the infectious activity in chimpanzees. RESULTS: One unit each (273-282 ml) of fresh-frozen plasma from 2 blood donors or a pool from 13 donors to make a unit, which contained high-titered antibody to HCV but without HCV RNA detectable by NAT, did not infect any of 3 chimpanzees. Two chimpanzees were infected, however, when they were inoculated with 1 ml of serum from a blood donor in the 'window period' of HCV infection and containing 7.0 x 10(6) copies/ml of HCV RNA. The preacute phase serum from 1 of them harvested 7 weeks after the inoculation was titrated in 2 chimpanzees, and an inoculum containing approximately 2 x 10(1) copies of HCV RNA could transmit infection to both of them. CONCLUSION: Approximately 20 copies of HCV can transmit infection to recipients, which needs to be taken into consideration in planning the screening of blood units for HCV RNA by NAT. Although the sensitivity of present NAT could be improved further, there would be a limit of it in detecting a low-level HCV RNA in the window period of donors with the infectious capacity in recipients.

High throughput screening of 16 million serologically negative blood donors for hepatitis B virus, hepatitis C virus and human immunodeficiency virus type-1 by nucleic acid amplification testing with specific and sensitive multiplex reagent in Japan.

Nationwide nucleic acid amplification testing (NAT) for hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) of blood donated voluntarily after serological screening was implemented on July 1st 1999 for transfusion and plasma fractionation by the Japanese Red Cross blood transfusion services. From February 1st 2000, HBV, HCV and HIV-1 NAT screening of pools of 50 negative serologically screened donated blood was started and the results were reported within 1 day after blood donation. Systems were established for rapid shipment, electronic communication, automated specimen preparation, pooling and automated amplification and detection. At present, NAT screening is carried out within 1 day after donation. This report describes the blood screening system by NAT and the results obtained from over 16 million blood samples using simultaneous screening for HBV, HCV and HIV-1 with multiplex reagent. Between February 1, 2000 and December 31, 2002, 16012175 serologically negative units were tested by NAT. 308 units with Hepatitis B virus DNA (HBV DNA) were detected. The sensitivity of 50 pool NAT screening with input volume of 0.2 ml is significantly higher than that of highly sensitive HBsAg testing. 46 cases with HCV RNA and six cases with HIV-1 RNA were detected. These cases were not detected by HCV antibody and HIV-1 antibody screening. The false positive rate was 0.18%. The NAT system was developed from serological screening test negative non-remunerated voluntary donations. We supply blood products to medical organizations after screening by NAT for HBV, HCV and HIV-1 for transfusion and source plasma for fractionation. This is the first automated integrated system for prevention of transfusion transmitted HBV, HCV and HIV-1 infections, by NAT screening.