REANALYSIS OF DOSE-RESPONSE DATA FROM THE IRAQI METHYLMERCURY POISONING EPISODE

被引:37
作者
CRUMP, K [1 ]
VIREN, J [1 ]
SILVERS, A [1 ]
CLEWELL, H [1 ]
GEARHART, J [1 ]
SHIPP, A [1 ]
机构
[1] ELECT POWER RES INST,PALO ALTO,CA 94303
关键词
METHYLMERCURY; RISK ASSESSMENT; BENCHMARK;
D O I
10.1111/j.1539-6924.1995.tb00345.x
中图分类号
R1 [预防医学、卫生学];
学科分类号
1004 ; 120402 ;
摘要
Applying a hockey stick parametric dose-response model to data on late or retarded development in Iraqi children exposed in utero to methylmercury, with mercury (Hg) exposure characterized by the peak Hg concentration in mothers' hair during pregnancy, Cox ed al. calculated the ''best statistical estimate'' of the threshold for health effects as 10 ppm Hg in hair with a 95% range of uncertainty of between 0 and 13.6 ppm.((1)) A new application of the hockey stick model to the Iraqi data shows, however, that the statistical upper limit of the threshold based on the hockey stick model could be as high as 255 ppm. Furthermore, the maximum likelihood estimate of the threshold using a different parametric model is virtually zero. These and other analyses demonstrate that threshold estimates based on parametric models exhibit high statistical variability and model dependency, and are highly sensitive to the precise definition of an abnormal response. Consequently, they are not a reliable basis for setting a reference dose (RfD) for methylmercury. Benchmark analyses and statistical analyses useful for deriving NOAELs are also presented. We believe these latter analyses-particularly the benchmark analyses-generally form a sounder basis for determining RfDs than the type of hockey stick analysis presented by Cox et al. However, the acute nature of the exposures, as well as other limitations in the Iraqi data suggest that other data may be more appropriate for determining acceptable human exposures to methylmercury.
引用
收藏
页码:523 / 532
页数:10
相关论文
共 24 条
[2]   DOSE-RESPONSE ASSESSMENT FOR DEVELOPMENTAL TOXICITY .2. COMPARISON OF GENERIC BENCHMARK DOSE ESTIMATES WITH NO OBSERVED ADVERSE EFFECT LEVELS [J].
ALLEN, BC ;
KAVLOCK, RJ ;
KIMMEL, CA ;
FAUSTMAN, EM .
FUNDAMENTAL AND APPLIED TOXICOLOGY, 1994, 23 (04) :487-495
[3]   METHYLMERCURY POISONING IN IRAQ - INTERUNIVERSITY REPORT [J].
BAKIR, F ;
DAMLUJI, SF ;
AMINZAKI, L ;
MURTADHA, M ;
KHALIDI, A ;
ALRAWI, NY ;
TIKRITI, S ;
DHAHIR, HI ;
CLARKSON, TW ;
SMITH, JC ;
DOHERTY, RA .
SCIENCE, 1973, 181 (4096) :230-241
[4]  
CLARKSON TW, 1991, MEASUREMENTS RISKS, P111
[5]   DOSE-RESPONSE ANALYSIS OF INFANTS PRENATALLY EXPOSED TO METHYL MERCURY - AN APPLICATION OF A SINGLE COMPARTMENT MODEL TO SINGLE-STRAND HAIR ANALYSIS [J].
COX, C ;
CLARKSON, TW ;
MARSH, DO ;
AMINZAKI, L ;
TIKRITI, S ;
MYERS, GG .
ENVIRONMENTAL RESEARCH, 1989, 49 (02) :318-332
[6]  
COX DR, 1984, MONOGRAPHS STATISTIC
[7]  
CRUMP K, 1994, IN PRESS RISK AN DEC
[8]   A NEW METHOD FOR DETERMINING ALLOWABLE DAILY INTAKES [J].
CRUMP, KS .
FUNDAMENTAL AND APPLIED TOXICOLOGY, 1984, 4 (05) :854-871
[9]  
GAYLOR DW, 1990, NEUROTOXICOLOGY, V11, P211
[10]  
GRANDJEAN P, 1992, ARCH ENVIRON HEALTH, V47, P195