ATSDR, ICF Kaiser International (under the ITER PR column), NSF International, RIVM, and U.S. EPA have evaluated the noncancer oral toxicity data for methylmercury. EPA derived a reference dose (RfD) of 0.0001 mg/kg-day based on a Faroe Islands study of children exposed in utero from mothers who were chronically exposed to methylmercury through ingestion of fish and pilot whale meat. EPA used benchmark dose modeling to estimate the 95\% lower confidence limit of the methylmercury concentration in maternal blood that resulted in a 5\% increased incidence of neuropsychological impairments in infants born of women who had consumed fish and pilot whale meat. Maternal daily dietary intake levels were used as the dose surrogate for the observed developmental effects in the children exposed in utero. The daily dietary intake levels were calculated from blood concentrations measured in the mothers with supporting additional values based on their hair concentrations. EPA used an uncertainty factor of 10 to account for pharmacokinetic variability and uncertainty in estimating an ingested mercury dose from cord-blood mercury concentration and for pharmacodynamic variability and uncertainty. NSF International has adopted EPA's RfD of 0.0001 mg/kg-day for methylmercury (US EPA, 2001).

ATSDR based its value on a study in the Seychelles Islands of children exposed in utero from mothers who were chronically exposed to methylmercury through ingestion of fish. From this study ATSDR designated the median maternal hair concentration from the highest exposure group as a NOAEL. ATSDR used a conversion equation to estimate daily intake value and used an uncertainty factor of 4.5 [1.5 each for variability in hair-to-blood ratios among women and fetuses in the U.S. population, for the remainder of any inter-individual variability (i.e., pharmacodynamics) in the U.S. population, and for the possibility that the domain-specific tests, as employed extensively in the Faroe Islands but not the Seychelles, which used primarily neurobehavioral tests of global function, might be able to detect very subtle neurological effects not tested for in the 66-month Seychelles cohort] to determine the minimal risk level (MRL) of 0.0003 mg/kg/day.

RIVM based its tolerable daily intake (TDI) on the same study and estimated NOAEL as ATSDR, but used an uncertainty factor of 10 for intraspecies variation, resulting in a TDI of 0.0001 mg/kg-day (which is the same as EPA's RfD).

ICF Kaiser International (under the ITER PR column) also used the Seychelles data and used benchmark dose modeling to estimate the 95\% lower confidence limit of the methylmercury concentration in maternal hair that resulted in a 10\% increased incidence of neurological deficits in infants. ICF Kaiser International, unlike any of the other organizations, used PBPK (physiologically-based pharmacokinetic) modeling and Monte Carlo analysis to develop a distribution of ingestion rates. The distribution is the probability that a given rate of ingestion of fish containing methylmercury will result in levels in hair at a benchmark dose of 21 ppm. ICF Kaiser International applied a 3-fold uncertainty factor because of health concerns raised by other studies on fish eating populations and determined a site specific reference dose (RfD) range of 0.0003 to 0.001 mg/kg-day. An independent peer review panel through TERA's ITER Peer Review program has approved the ICF Kaiser International value and supporting documentation thereby qualifying it for inclusion in this database.

Noncancer Oral Specifics:

ATSDR

DCE:
See MRL Worksheet in Toxicological Profile, Appendix A, pp. A-10 through A-24. Available at http://www.atsdr.cdc.gov/toxprofiles/tp46-a.pdf.

QEST:
See MRL Worksheet in Toxicological Profile, Appendix A, pp. A-10 through A-24. Available at http://www.atsdr.cdc.gov/toxprofiles/tp46-a.pdf.

PEER:
The ATSDR Toxicological Profile has undergone the standard internal agency reviews and has been externally reviewed by a peer review panel. In addition, the studies considered by ATSDR for use in estimating a chronic oral MRL for methylmercury underwent two stringent reviews by recognized experts in the environmental health field.

BIB:
Davidson, P.W., G.J. Myers, C. Cox, et al. 1998. Effects of prenatal and postnatal methylmercury exposure from fish consumption on neurodevelopment: outcomes at 66 months of age in the Sechelles child development study. JAMA. 280(8): 701-707.

MOREI:
ATSDR (Agency for Toxic Substances and Disease Registry). 1999. Toxicological Profile for Mercury. Update. U.S. Department of Health and Human Services, Public Health Service. March. Available at http://www.atsdr.cdc.gov/toxprofiles/tp46.html .

For the list of ATSDR minimal risk levels (MRLs), see http://www.atsdr.cdc.gov/mrls/index.html .

Noncancer Oral Specifics:

ITER PR

DCE:
This assessment was developed by ICF Kaiser International. An independent peer review panel through TERA's ITER Peer Review program has approved the ICF Kaiser International value and supporting documentation thereby qualifying it for inclusion in this database.

The neurotoxic effects of ingested methylmercury have been well-documented in major poisoning incidents in Iraq (Bakir et al. 1973; Amin-Zaki et al. 1974) and in Minimata and Niigata, Japan (Harada 1978; 1982). Following exposure at nonlethal levels, methylmercury produced neurological signs and symptoms in adults that ranged from paresthesia, usually the first symptom to appear, to ataxia, dysarthria, and constriction of visual fields (Harada 1978, 1982; Bakir et al. 1973; Amin-Zaki et al. 1979). Neurological effects were also noted in children exposed in utero, some of whom were borne to mothers who were clinically asymptomatic during pregnancy (Harada 1978, 1995; Amin-Zaki et al. 1974, 1976, 1979; Marsh et al. 1980, 1981, 1987). These data, as well as data in experimental animals (Spyker et al. 1972; Bornhausen et al. 1980; Gunderson et al. 1986; Rice and Gilbert 1990; Evans et al. 1997), suggest that neurodevelopmental effects may result from fetal exposure at maternal methylmercury levels as much as an order of magnitude lower than those associated with the earliest effects in nonpregnant adults (Clarkson 1989, 1992). Therefore, it appears that the critical effect for methylmercury toxicity is its impact on neurodevelopment and that a reference dose (RfD) for methylmercury ingestion should be based on data for children exposed in utero.

Epidemiological studies that evaluated neurodevelopmental effects in children exposed to methylmercury in utero have been conducted in Iraq (Amin-Zaki et al. 1974, 1976, 1979; Marsh et al. 1980, 1981, 1987; Seafood Safety 1991), Canada (McKeown-Eyssen et al. 1983), New Zealand (Kjellstrom et al. 1986, 1989), the Seychelles Islands (Myers et al. 1995, 1997; Davidson et al. 1995), Peru (Marsh et al. 1995), and the Faroe Islands (Grandjean et al. 1997). Maternal exposure in the Iraqi population was acute in nature and resulted from ingestion of methylmercury-contaminated bread, while in the other populations chronic exposure to methylmercury resulted from ingestion of fish and shellfish and/or marine mammals. Since the RfD documented here was intended to be a site-specific RfD for a population chronically exposed to methylmercury via fish ingestion, studies in populations similarly exposed were preferred. However, other factors were also considered, such as cohort size, quality of exposure characterization, potential for confounding factors, availability of data suitable for dose-response analysis, and relative sensitivity of the endpoint measured. The Iraqi study was not selected for several reasons, including: 1) the retrospective nature of the study; 2) the small cohort size (81 mother-infant pairs); 3) the acute nature of the exposure, entailing, therefore, the possibility that the dynamics of fetal exposure and toxicity could be much different than for a relatively constant chronic exposure; 4) the dissimilarity of the route of exposure (contaminated bread) to the exposure route of interest (fish ingestion); and 5) the fact that the reported results for developmental milestones (walking and talking) were subject to recall bias and misclassification. The studies in Peru (Marsh et al. 1995) and Canada (McKeown-Eyssen et al. 1983) examined only clinically observable signs and symptoms, such as developmental milestones for walking and talking or neurophysiological exams. When controlled for confounders, no association with methylmercury exposure was reported in either of these published studies.

Three studies, in which mothers were exposed chronically to methylmercury through fish ingestion (Kjellstrom et al. 1989; Davidson et al. 1995; Grandjean et al. 1997), reported the results of neuropsychological and neurobehavioral tests administered to children exposed in utero in order to assess the presence of more subtle neurodevelopmental effects. The Seychelles study (Myers et al. 1995, 1997; Davidson et al. 1995) was a large, longitudinal study (approximately 740 mother-infant pairs) conducted in a fairly stable population with exceptional prenatal and antenatal care. Exposure to methylmercury was chronic, likely multigenerational, and only through ingestion of fish and shellfish. Further, children were administered age-specific tests at several ages with the results of the test batteries reported in sufficient detail to be used in dose-response modeling. The New Zealand study was also a well-conducted study in a fish-eating population and provided quantitative information for dose-response modeling. However, cohort was smaller than the Seychelles (228 mother-infant pairs) and a single individual and ethnicity influenced the outcome. The Faroe Islands study was also a large study (917 mother-infant pairs) and also administered a battery of neurobehavioral and neurophysiological tests. This population was exposed to methylmercury through ingestion of both fish and marine mammals, which also contained high levels of PCBs. However, the data as reported were not useable for dose-response modeling. Moreover, potential confounding from co-exposure to PCBs, in particular for the subgroup designated as less than 10 ppm methylmercury in maternal hair, was considered a serious limitation.

After consideration of these three most relevant studies for the derivation of a RfD, the Seychelles study was preferred as the critical study upon which to base the RfD. Extensive dose-response analyses have already been conducted for the New Zealand cohort (Crump et al. 1998); however, because of the larger cohort for the Seychelles and other considerations noted above, the Seychelles study was chosen. The Faroe Islands study (Grandjean et al. 1997), which did report statistically significant associations between the ingestion of methylmercury in pilot whale meat and neurological effects, could not be used for dose-response modeling due to unavailability of the necessary data. However, the information provided by the Faroe Islands and New Zealand studies was used in the evaluation of the uncertainty in the estimates of intake.

QEST:
The study conducted in the Seychelles Islands (Davidson et al., 1995, Myers et al., 1995) was subjected to quantitative dose-response analysis using the Benchmark Dose method (Crump 1984, 1995). This study consisted of a cohort of 740 mother-infant pairs, with maternal hair mercury levels ranging from 0.5 to 26.7 ppm (median 5.94 ppm, mean and standard deviation - 6.85 +/- 4.50 ppm) (Cernichiari et al. 1995). A battery of neurological tests was administered to the infants at 6.5, 19, and 29 months of age. At 6.5 months of age, the infants were administered the Denver Developmental Screening Test-Revised (DDST-R) and the Fagan's test of visual recognition memory (Infantest). The DDST-R, when administered early in infancy, has good predictability of future cognitive outcomes (Marsh et al. 1995). At both 19 and 29 months, the Bayley Scales of Infant Development (BSID) were administered. These tests have been widely used as a measure of cognitive function (Marsh et al. 1995). Children were also given a general medical and a neurological examination. An advantage of using the Seychelles study for the quantitative derivation of an RfD is that the individual scores from the infants, along with the associated maternal hair level of methylmercury are available in the published reports. Additional advantages of this cohort include the fact that there were a limited number of potential confounders, which were identified a priori and controlled for in the analyses of the results. Therefore the data as reported are highly suitable for dose-response analysis using the Benchmark Dose method.

Evaluation of the Benchmark Dose method used in this analysis, as well as in the current USEPA RfD, has demonstrated that the resulting 95\% lower bound on the 10\% benchmark dose (BMDL) represents a conservative alternative to the traditional NOAEL, and that it is superior to the use of "average" or "grouped" exposure estimates when dose-response information is available, as is the case for the Seychelles study.

Benchmark Dose modeling over the wide range of neurological endpoints reported in the Seychelles study (Myers et al. 1995, Davidson et al. 1995) yielded a lowest BMDL for methylmercury in maternal hair of 21 ppm. This BMDL was then converted to an expected distribution of daily ingestion rates across a population of U.S. women of child-bearing age using Monte Carlo analysis with a physiologically based pharmacokinetic (PBPK) model of methylmercury (Gearhart et al. 1995) to evaluate the impact of interindividual pharmacokinetic variability. The method used for estimating an ingestion rate that corresponded to the BMDL was similar to the procedure applied in the current USEPA RfD except that a PBPK model was used instead of an empirical pharmacokinetic model, and an analysis of the variability in the relationship between ingestion rate and hair concentration was used to define a distribution of ingestion rates instead of predicting only a "best estimate."

The PBPK model used in the analysis (Gearhart et al. 1995) included a maternal model and a fetal sub-model whose compartments grow during the time of gestation. The model is able to accurately simulate reported data on methylmercury concentrations in maternal hair, maternal blood, and infant blood during pregnancy. Probability distributions were developed for each of the PBPK model parameters and used in a Monte Carlo analysis (Latin hypercube method) to determine the impact of pharmacokinetic parameter variability on the relationship between methylmercury ingestion rate and hair concentration.

The resulting distribution of ingestion rates at the BMDL of 21 ppm had a geometric mean of 1.60 ug/kg/day with a geometric standard deviation of 1.33; the 1st, 5th, and 10th percentiles of the distribution were 0.86, 1.04, and 1.15 ug/kg/day. In place of the use of an uncertainty factor of 3 for pharmacokinetic variability, as is done in the current RfD, one of these lower percentiles of the daily ingestion rate distribution provides a scientifically-based, conservative basis for taking into consideration the impact of pharmacokinetic variability across the population of U.S. women of child- bearing age.

For this assessment, an uncertainty factor of 3 was applied. This factor was included to address concerns regarding the possibility of chronic sequelae as well as concerns raised by other studies of fish-eating populations. Additional factors for variability in human pharmacodynamics, and database inadequacy, specifically lack of a two-generation reproductive study, were not considered necessary. In the current analysis, the fetus is considered to represent a sensitive subpopulation, and variability in human pharmacokinetics has been explicitly accounted for by the use of a physiologically based pharmacokinetic model. A factor for lack of a two-generation reproductive study is considered unnecessary because: 1) the putative mechanism of neurodevelopmental effects (the most sensitive endpoint) would not be expected to be passed to following generations; 2) there is no evidence that methylmercury exposures would result in heritable effects on germ cells; and 3) information from epidemiological studies suggests that chronic low-level exposures to methylmercury via fish ingestion over multiple generations have had no observable effect on reproduction. The weight of evidence of the literature on methylmercury also indicates that the development of chronic sequelae is dose-dependent, and that such effects are highly unlikely in populations exposed in utero to low methylmercury levels from maternal consumption of fish containing methylmercury. However, while concerns regarding the possibility of chronic sequelae are not supported by the available data, neither can they be absolutely ruled out. Therefore, the application of an uncertainty factor of 3 was considered in part to account for some residual concerns regarding chronic sequelae.

The uncertainty factor of 3 also provides a measure of conservatism to address the concerns raised by other studies, e.g. the Faroe Islands report (Grandjean et al. 1997). Although there can be high confidence in the Benchmark-estimated NOAEL of 21 ppm in the Seychelles study, some results in the New Zealand and Faroe Islands studies could be construed to suggest the possibility of effects at maternal hair concentrations below 10 ppm. The use of an uncertainty factor of 3 is equivalent to using a NOAEL of 7 ppm in maternal hair, which provides additional protection against the possibility that effects could occur at lower concentrations in some populations.

Recommended RfD Distribution

Based on the analysis described above, and using an uncertainty factor of 3, the distribution of acceptable daily ingestion rates (RfDs) recommended to serve as the basis for site-specific risk management decisions at the Alcoa Point Comfort Operations, Texas, ranges from approximately 0.3 to 1.1 ug/kg-day (0.0003 to 0.001 mg/kg-day), with a population median (50th percentile) of 0.5 ug/kg-day.

This RfD is for humans chronically ingesting fish containing methyl mercury, and has been developed specifically for Lavaca Bay, Texas, USA. This distribution shown in the figure and table illustrate the probability that a given rate of ingestion of fish containing methyl mercury will result in a level of 7 ppm mercury in maternal hair (equivalent to a benchmark dose of 21 ppm divided by an uncertainty factor of 3). The science underlying this RfD generates a distribution, not a single value. Selection of any single percentile or number as the RfD is a risk management decision or a regulatory policy.

Click on the following link http://www.tera.org/iter/mehgtable.html for a table that shows that the RfD derived in the ICF analysis ranges from 0.3 to 1 ug/kg-day, and that 0.5 is the 50th percentile, 0.4 is the 10th percentile, etc.

Click on the following link http://www.tera.org/iter/mehgfigure.html for a figure which shows the distribution of methyl mercury ingestion rates associated with the 7 ppm mercury in maternal hair derived by ICF in its pharmacokinetic analysis. The value of 7 ppm in hair is the BMDL from the Seychelles (21 ppm) divided by a factor of 3 to account for some uncertainties.

PEER:
ITER Independent Peer Review: 1/12/98; 2/26/98

Meeting summary available at http://www.tera.org/peer/methylmercury.html.

BIB:
Amin-Zaki L, Elhassani S, Majeed MA, Clarkson TW, Doherty RA, Greenwood M. 1974. Intra-uterine methylmercury poisoning in Iraq. Pediatrics 54:587-595.

Amin-Zaki L, Elhassani S, Majeed M, Clarkson T, Doherty R, Greenwood M. 1976. Perinatal methylmercury poisoning in Iraq. Am J Dis Child 130:1070-1076.

Amin-Zaki L, Majeed M, Elhassani S, Clarkson T, Greenwood M, Doherty R. 1979. Prenatal methylmercury poisoning. Am J Dis Child 133:172-177.

Bakir F, Damluji S, Amin-Zaki L, et al. 1973. Methylmercury poisoning in Iraq. Science 181:230-241.

Bornhausen M, Musch H, Greim H. 1980. Operant behavior performance changes in rats after prenatal methylmercury exposure. Toxicol Appl Pharmacol 56:305-310.

Cernichiari E, Brewer R, Myers GJ, Marsh DO, Lapham LW, Cox C, Shamlaye CF, Berlin M, Davidson PW, Clarkson TW. 1995. Monitoring methylmercury during pregnancy: maternal hair predicts fetal brain exposure. NeuroToxicology 16:705-710.

Clarkson T. 1989. Mercury. J Am Coll Toxicol 8:1291-1295.

Clarkson TW. 1992. Mercury: major issues in environmental health. Environ Health Perspect 100:31-38.

Crump K. 1984. A new method for determining allowable daily intakes. Fund Appl Toxicol 4:854-871.

Crump K. 1995. Calculation of benchmark doses from continuous data. Risk Anal 15:79-89.

Crump K, Kjellstrom T, Shipp A, Silvers A, Stewart A. 1998. Influence of prenatal mercury exposure upon scholastic and psychological test performance: statistical analysis of a New Zealand cohort. Risk Anal (submitted).

Davidson P, Myers G, Cox C, Shamlaye C, Marsh D, Tanner M, Berlin M, Sloane-Reeves J, Cernichiari E, Choisy O, Choi A, Clarkson T. 1995. Longitudinal neurodevelopmental study of Seychellois children following in utero exposure to methylmercury from maternal fish ingestion: outcomes at 19 and 29 months. NeuroToxicology 16:677-688.

Evans HL, Garman RH, Weiss B. 1977. Methylmercury: Exposure duration and regional distribution as determinants of neurotoxicity in nonhuman primates. Toxicol Appl Pharmacol 41:15-33.

Gearhart J, Clewell H, Crump K, Shipp A, Silvers A. 1995. Pharmacokinetic dose estimates of mercury in children and dose-response curves of performance tests in a large epidemiological study. In: Porcella DB, Huckabee JW, Wheatley B, eds. Mercury as a Global Pollutant. Kluwer Academic Publishers, Boston. Pp. 49-58.

Grandjean P, Weihe P, White R, Debes F, Araki S, Yokoyama K, Murata K, Sorensen N, Dahl R, Jorgensen P. 1997. Cognitive deficit in 7-year-old children with prenatal exposure to methylmercury. Neurotoxicol Teratol 20:1-12.

Gunderson V, Grant K, Burbacher T, Fagan J, Mottet N. 1986. The effect of low-level prenatal methylmercury exposure on visual recognition memory in infant crab-eating macaques. Child Dev 57:1076-1083.

Harada M. 1995. Minamata disease: methylmercury poisoning in Japan caused by environmental pollution. Crit Rev Toxicol 25:1-24.

Harada M. 1982. Minamata disease: Organic mercury poisoning caused by ingestion of contaminated fish. In Jellife EF, Jellife DB, eds. Adverse Effects of Food, Plenum Press, New York NY. Pp 135-148.

Harada M. 1978. Congenital Minamata disease: Intrauterine methylmercury poisoning. Teratology 18:285-288.

Kjellstrom T, Kennedy P, Wallis S, Mantell C. 1986. Physical and mental development of children with prenatal exposure to mercury from fish. Stage 1: Preliminary tests at age 4. National Swedish Environmental Protection Board, Report 3080. Solna, Sweden.

Kjellstrom T, Kennedy P, Wallis S, Stewart A, Friberg L, Lind B, Wutherspoon T, Mantell C. 1989. Physical and Mental Development of Children with Prenatal Exposure to Mercury from Fish. Stage 2: Interviews and Psychological Tests at Age 6. Report 3642. National Swedish Environmental Board, Solna. 112 pp.

Marsh D, Myers G, Clarkson T, Amin-Zaki L, Al-Tikriti S, Majeff M. 1980. Fetal methylmercury poisoning: Clinical and toxicological data on 29 cases. Ann Neurol 7:348-353.

Marsh D, Myers G, Clarkson T, et al. 1981. Dose-response relationship for human fetal exposure to methylmercury. Clin Toxicol 18:1311-1318.

Marsh D, Clarkson T, Cox C, Myers G, Amin-Zaki L, Al-Tikriti S. 1987. Fetal methylmercury poisoning. Relationship between concentration in single strands of maternal hair and child effects. Arch Neurol 44:1017-1022.

Marsh D, Turner M, Smith J, Allen P, Richdale N. 1995. Fetal methylmercury study in a Peruvian fish-eating population. Neurotoxicology 16:717-726.

McKeown-Eyssen G, Ruedy J, Neims A. 1983. Methyl mercury exposure in northern Quebec. II. Neurologic findings in children. Am J Epidemiol 118:470-479.

Myers G, Davidson P, Shamlaye C, et al. 1997. Effects of prenatal methylmercury exposure from a high fish diet on developmental milestones in the Seychelles Child Development study. NeuroToxicology 18:819-830.

Myers G, Marsh D, Davidson P, Cox C, Shamlaye C, Tanner M, Choi A, Cernichiari E, Choisy O, Clarkson T. 1995. Main neurodevelopmental study of Seychellois children following in utero exposure to methylmercury from a maternal fish diet: outcome at six months. NeuroToxicology 16:653-664.

Rice DC, Gilbert SG. 1990. Effects of developmental exposure to methylmercury on spatial and temporal visual function in monkeys. Toxicol Appl Pharmacol 102:151-163.

Seafood Safety. 1991. Committee on Evaluation of the Safety of Fishery Products, Chapter on Methylmercury: FDA Risk Assessment and Current Regulations. National Academy Press, Washington, DC. Pp. 196-221.

Spyker JM, Sparber SH, Goldberg AM. 1972. Subtle consequences of methylmercury exposure: behavioral deviations in offspring of treated mothers. Science 177:621-623.

MOREI:
ICF Kaiser. 1998. Site-Specific Reference Dose for Methylmercury for Fish-Eating Populations. Ruston, Louisiana. March.

Copies of this document are available at a cost of $75.00, to cover reproduction and mailing, from: KS Crump Group, Inc.

ICF Kaiser International

602 East Georgia Avenue

Ruston, Louisiana, 71270

Phone: (318) 255-4800

FAX: (318) 255-4960

http://www.icfconsulting.com.

Noncancer Oral Specifics:

NSF Intl

DCE:
NA

QEST:
NSF International adopts the US EPA IRIS reference dose (RfD) values for certain chemicals as its basis for deriving acceptable long-term exposure levels for these chemicals in drinking water. If the US EPA has both a noncancer oral RfD and a cancer risk level, NSF International will adopt the more conservative of the two, which is usually the cancer risk value.

PEER:
Since the US EPA IRIS RfD values have been internally and externally peer reviewed before being published on IRIS, NSF International adopts EPA's RfDs without additional peer review of its own. However, prior to the publication of NSF International's drinking water levels in the NSF International drinking water standards NSF/ANSI 60 and 61 (2005), both the NSF International Joint Committee on Drinking Water Additives and the Council of Public Health Consultants (CPHC) recommended to adopt the US EPA IRIS RfD values.

BIB:
U.S. EPA, 2001. Integrated Risk Information System (IRIS). Online. National Center for Environmental Assessment, Washington, DC. Available at http://www.epa.gov/iris/subst/0073.htm .

MOREI:
NSF/ANSI Standard 60. 2005. Drinking Water Treatment Chemicals - Health Effects. NSF International, Ann Arbor, MI. Available for a fee at: http://www.techstreet.com/cgi-bin/detail?product\_id=1247346.

NSF/ANSI Standard 61. 2005. Drinking Water System Components - Health Effects. NSF International, Ann Arbor, MI. Available for a fee at: http://www.techstreet.com/cgi-bin/detail?product\_id=1247365.

Noncancer Oral Specifics:

RIVM

PEER:
The RIVM toxicological profile has undergone internal reviews.

BIB:
ATSDR, 1999. Toxicological Profile for Mercury (Update). Agency for Toxic Substances Disease Registry, US Public Health Service.

MOREI:
Baars AJ et al. 2001. Re-evaluation of human-toxicological maximum permissible risk levels. RIVM report no. 711701025, National Institute of Public Health and the Environment, Bilthoven, The Netherlands, March 2001, p 70-74. Available at http://www.rivm.nl/bibliotheek/rapporten/711701025.pdf or at http://www.rivm.nl/en/ (click on Search, type "711701025", then click on document).

Previous source document:

Vermeire, TG, ME van Apeldoorn, JC de Fouw and PJCM Janssen. "Voorstel voor de humaan-toxicologische onderbouwing van C-(toetsings)warden" (In Dutch). RIVM report no. 725201005. National Institute of Public Health and the Environment, Bilthoven, The Netherlands, February 1991, p 67-68. Report can be ordered from RIVM (see http://www.rivm.nl/en/ click on Publications, then click on "How to order" for instructions).

Noncancer Oral Specifics:

U.S.EPA

BIB:
Budtz-Jorgensen, E; Keiding, N; Grandjean, P; et al. (1999) Methylmercury neurotoxicity independent of PCB exposure. [Letter]. Environ Health Perspect 107(5):A236-237.

Grandjean, P; Weihe, P; White, R; et al. (1997) Cognitive deficit in 7-year-old children with prenatal exposure to methylmercury. Neurotoxicol Teratol 20:1-12.

MOREI:
Details on this chemical's assessment are available on U.S. EPA's Integrated Risk Information System (IRIS).