List of IRIS Substances 

Search IRIS by Keyword

IRIS Summaries/Toxicological 

Reviews

Entire IRIS Website

Category (section) Status Last Revised

You are here: EPA Home Research Environmental Assessment IRIS IRIS Summaries

view QuickView 

Reference Dose for Chronic Oral Exposure (RfD) 

You will need Adobe Reader to view some of the files on this page. See EPA's PDF 

page to learn more.

Note: A Support Document for Methylmercury can be found on EPA's Office of Water Web site. The 

Summary and Response to the Peer Review for Methylmercury is also available in Adobe PDF format (23 

Pages, 63 Kbytes). 

Similar documents can be found in the List of Available IRIS Toxicological Reviews. 

0073

Methylmercury (MeHg); CASRN 22967-92-6

Human health assessment information on a chemical substance is included in the IRIS database 

only after a comprehensive review of toxicity data, as outlined in the IRIS assessment 

development process. Sections I (Health Hazard Assessments for Noncarcinogenic Effects) and II 

(Carcinogenicity Assessment for Lifetime Exposure) present the conclusions that were reached 

during the assessment development process. Supporting information and explanations of the 

methods used to derive the values given in IRIS are provided in the guidance documents located 

on the IRIS website. 

STATUS OF DATA FOR Methylmercury 

File First On-Line 01/31/1987

Oral RfD Assessment (I.A.) on-line 07/27/2001 

Inhalation RfC Assessment (I.B.) no data 07/27/2001

Carcinogenicity Assessment (II.) on-line 05/01/1995

_I. Chronic Health Hazard Assessments for Noncarcinogenic Effects

Integrated Risk Information System

http://www.epa.gov/iris/subst/0073.htm

Last updated on Friday, October 31, 2014

http://www.epa.gov/iris/subst/0073.htm
Critical Effect Experimental Doses*

_I.A. Reference Dose for Chronic Oral Exposure (RfD)

Substance Name — Methylmercury (MeHg) 

CASRN — 22967-92-6 

Last Revised — 07/27/2001

The oral Reference Dose (RfD) is based on the assumption that thresholds exist for certain toxic 

effects such as cellular necrosis. It is expressed in units of mg/kg-day. In general, the RfD is an 

estimate (with uncertainty spanning perhaps an order of magnitude) of a daily exposure to the 

human population (including sensitive subgroups) that is likely to be without an appreciable risk 

of deleterious effects during a lifetime. Please refer to the Background Document for an 

elaboration of these concepts. RfDs can also be derived for the noncarcinogenic health effects of 

substances that are also carcinogens. Therefore, it is essential to refer to other sources of 

information concerning the carcinogenicity of this substance. If the U.S. EPA has evaluated this 

substance for potential human carcinogenicity, a summary of that evaluation will be contained in 

Section II of this file. 

__I.A.1. Oral RfD Summary

UF MF RfD

Developmental

neuropsychological 

impairment

Human epidemiological 

studies (Grandjean et al., 

1997; Budtz-Jørgensen et 

al., 1999a)

Benchmark Dose: BMDL05

range of 46-79 ppb in 

maternal blood for different

neuropsychological effects in the 

offspring at 7 years of age, 

corresponding to a range of 

maternal daily intakes of 

0.857-1.472 μg/kg-day

10 1 

 1E-4 

mg/kg-day 

(0.0001 

mg/kg-day)

*Conversion Factors and Assumptions —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. This 

conversion is explained in the text below. A benchmark dose approach (BMD) was used rather than a no-observed-adverseeffect level/lowest-observed-adverse-effect level (NOAEL/LOAEL) approach to analyze the neurological effects in children 

as the response variable. This analysis is also explained in the text below.

This assessment updates the 1995 RfD assessment on IRIS and is the same as the RfD that was 

based on the study of a poisoning episode in Iraq in which developmental neurotoxicity was 

observed following ingestion of methylmercury-treated grain (Marsh et al., 1987).

__I.A.2. Principal and Supporting Studies (Oral RfD)

Congress directed EPA, through the House Appropriations Report for Fiscal Year 1999, to contract 

with the National Research Council (NRC), a body of the National Academy of Sciences, to 

evaluate the available data on the health effects of methylmercury, with particular emphasis on 

new data since the publication of the Mercury Study Report to Congress (MSRC) (U.S. EPA, 

1997). NRC was asked to provide recommendations regarding issues relevant to the derivation of 

an appropriate RfD for methylmercury. The NRC report, "Toxicological Effects of Methylmercury," 

was released to the public on July 11, 2000 (NRC, 2000). This assessment reported here relied on 

the quantitative analyses performed by the NRC, as described in that report. 

http://www.epa.gov/iris/subst/0073.htm
Methylmercury is a highly toxic substance; a number of adverse health effects associated with 

exposure to it have been identified in humans and in animal studies. Most extensive are the data 

on neurotoxicity, particularly in developing organisms. The nervous system is considered to be 

the most sensitive target organ for which there are data suitable for derivation of an RfD. 

There are three epidemiological studies for which quantitative analyses have become available 

since EPA's derivation of an RfD in 1995 (NRC, 2000). These longitudinal, developmental studies 

were conducted in the Seychelles Islands, the Faroe Islands, and New Zealand. The subjects of 

the Seychelles longitudinal prospective study were 779 mother-infant pairs from a fish-eating 

population (Myers et al., 1995a-c, 1997; Davidson et al., 1995, 1998). Infants were followed 

from birth to 5.5 years of age, and assessed at various ages on a number of standardized 

neuropsychological endpoints. The independent variable was maternal-hair mercury levels. The 

Faroe Islands study was a longitudinal study of about 900 mother-infant pairs (Grandjean et al., 

1997). The main independent variable was cord-blood mercury; maternal-hair mercury was also 

measured. At 7 years of age, children were tested on a variety of tasks designed to assess 

function in specific behavioral domains. The New Zealand study was a prospective study in which 

38 children of mothers with hair mercury levels during pregnancy greater than 6 ppm were 

matched with children whose mothers had lower hair mercury levels (Kjellstrom et al., 1989, 

1986). At 6 years of age, a total of 237 children were assessed on a number of 

neuropsychological endpoints similar to those used in the Seychelles study (Kjellstrom et al., 

1989). The Seychelles study yielded scant evidence of impairment related to in utero 

methylmercury exposure, whereas the other two studies found dose-related effects on a number 

of neuropsychological endpoints. In the assessment described here, emphasis is placed on the 

results of the Faroe Islands study, the larger of the two studies that identified methylmercuryrelated developmental neurotoxicity. Supporting evidence from the New Zealand study provides 

assurance that choosing this focus is the appropriate strategy for protecting public health. In 

addition, of all three studies an integrative analysis is set out later in this assessment report. 

EPA chose BMD analysis as the most appropriate method of quantifying the dose-effect 

relationship in these studies, which was also the recommendation of the NRC (2000). EPA chose 

the K power model for BMD analysis, with the constraint that K >= 1, such that the model 

precludes supralinearity. There is no identified mechanism by which methylmercury would 

produce a supralinear response; therefore the K power model was thought to have more 

biological plausibility compared with other models. A power of 1 provided the best fit of the 

Faroese data using the K power model (Budtz-Jørgensen et al., 1999b, 2000), so this model was 

used in this RfD derivation. A value of P0 = 0.05 was used: that is, the cutoff for abnormal 

response was set at the lowest 5% (5th percentile) of children. Most human characteristics, 

including children's neurodevelopmental abilities, have an approximately bell-shaped or "normal" 

distribution. Generally speaking, children who function at or below approximately the 5th

percentile are considered significantly developmentally compromised for the ability that is being 

measured (e.g., IQ < 75, or comparable standard scores for more specific abilities such as 

attention, language, or memory). A BMR of 0.05 was chosen for this assessment, which would 

result in a doubling of the number of children with a response at the 5th percentile of the 

population. This choice was particularly appropriate, because effects were identified on a number 

of neuropsychological endpoints in the offspring at approximately the same body burden in the 

mother. A benchmark dose lower limit (BMDL05) (the lower 95% confidence limit of the BMD05) 

was calculated for each endpoint described above from the three studies. 

DOSE CONVERSION

http://www.epa.gov/iris/subst/0073.htm
The biomarker of choice for the Faroese data was cord blood, and the BMDLs were reported in 

units of ppb mercury in cord blood. In order to calculate an RfD, it is necessary to convert this 

figure to an ingested daily amount that would result in exposure to the developing fetus at the 

BMDL level in terms of ppb mercury in blood. EPA chose the one-compartment model for dose 

conversion for this RfD. This model has shown reasonably good fit to data on mercury blood-level 

changes in human subjects during and after consumption of methylmercury-contaminated fish 

(Ginsberg and Toal, 2000). 

The model is described by the formula below: 

d= (c x b x V)/(A x f x bw) μg/kg/day

where

• d = daily dietary intake (expressed as μg of methylmercury)

• c = concentration in blood (expressed as μg/L)

• b = elimination constant (expressed as days-1)

• V = volume of blood in the body (expressed as liters)

• A = absorption factor (expressed as a unitless decimal fraction)

• f = fraction of absorbed dose taken up by blood (unitless)

• bw = body weight (expressed in kg) 

In this one-compartment model, all maternal compartments are compressed to one: namely, 

blood. It is assumed that the blood methylmercury concentration is at steady state. 

Concentration in blood (c)

The concentration in blood corresponds to the BMDL05. 

Fraction of mercury in diet that is absorbed (A)

After administration of radiolabeled methylmercuric nitrate in water to three healthy volunteers, 

uptake was reported to be >95 % (Aberg et al., 1969). This value is supported by experiments 

involving human volunteers conducted by Miettinen et al. (1971). It is generally believed that 

absorption of ingested methylmercury is high and not likely to vary a great deal. An absorption 

factor of 0.95 was used as in the Mercury Study Report to Congress (U.S. EPA, 1997). 

Fraction of the absorbed dose that is found in the blood (f)

Currently, four published reports address the fraction of absorbed methylmercury dose 

distributed to blood volume in humans. Kershaw et al. (1980) reported an average fraction of 

5.9% of absorbed dose in total blood volume, based on a study of five adult male subjects who 

ingested methylmercury-contaminated tuna. In a group of nine male and six female volunteers 

who had received 203Hg-methylmercury in fish, approximately 10% of the total mercury body 

burden was present in 1 L of blood in the first few days after exposure; this amount dropped to 

approximately 5% over the first 100 days (Miettinen et al., 1971). In another study, an average 

value of 1.14% for the percentage of absorbed dose per kg of blood was derived from data on 

subjects who consumed a known amount of methylmercury in fish over a 3-month period 

(Sherlock et al., 1984). Average daily intake in the study ranged from 43 to 233 μg/day, and 

there was a dose-related effect on percentage of absorbed dose that ranged from 1.03% to 

1.26% in 1 L of blood. Smith et al. (1994) administered radiolabeled methylmercury to seven 

http://www.epa.gov/iris/subst/0073.htm
subjects. The paper presented published modeled data rather than observations; the mean 

fraction of absorbed dose in blood was 7.7% (SD, 0.88%). 

Stern (1997) noted that although the Smith et al. (1994) and Kershaw et al. (1980) data could 

be fit by a log-normal distribution, the data sets were too small for a reasonable determination of 

the underlying distributions. Stern used the mean and standard deviation of those two data sets 

for average parameter values as inputs to the log-normal distribution; the average of the means 

is 0.067. Swartout and Rice (2000) used the observations published by Kershaw et al. (1980), 

Miettinen et al. (1971), and Sherlock et al. (1984) as adjusted for 5 L of blood as inputs with a 

log-triangular distribution. The median value was 5.9% or 0.059, close to the values of 0.05 used 

in the MSRC and by other groups (e.g., Berglund et al., 1971; WHO, 1990). 

EPA chose to use the median value of 0.059 published by Swartout and Rice (2000) for f in the 

dose conversion. 

Elimination constant (b)

Currently, five studies report clearance half-times for methylmercury from blood or hair: 

Miettinen et al. (1971), Kershaw et al. (1980), Al-Shahristani et al. (1974), Sherlock et al. 

(1984), and Smith et al. (1994). The clearance half-lives for blood in these reports are quite 

variable, ranging from 32 to 189 days. In the Al-Shahristani et al. (1974) study, 10% of the 

sample population had mercury half-lives of 110 to 120 days. Average mercury half-lives as 

gleaned from the five publications are 45 to 70 days. The MSRC (U.S. EPA, 1997) used an 

average elimination constant from four of the studies (data from Smith et al. [1994] were not 

used). The corresponding elimination constant of 0.014 days-1 also was noted to be the average 

of individual values reported for 20 volunteers ingesting from 42 to 233 μg mercury/day in fish 

for 3 months (Sherlock et al., 1982). 

Swartout and Rice (2000) applied a log-triangular distribution to the data from the five extant 

studies. They noted that the distribution was highly skewed and that the median was 53 days; 

the corresponding elimination constant was 0.013 days-1. 

Stern (1997) discussed the variability in the data sets. His analysis of variance indicated 

significant differences among the sets, which were eliminated when the Al-Shahristani data were 

removed. The author observed that the half-lives reported by Al-Shahristani were larger than 

those observed in the other studies. Stern offers the opinion that this difference may result from 

relatively large size of the Al-Shahristani data set as compared with the others. Stern says that 

an alternative explanation is that the Al-Shahristani data reflect a genetic polymorphism in the 

metabolism occurring with higher frequency in the Iraqi population, which was the subject of this 

study. In his analyses, Stern (1997) treated the Al-Shahristani data both separately and in 

combination with the data from the other four studies. He reported a mean elimination constant 

of 0.011 days-1 for the Al-Shahristani data alone; the combined data set mean elimination 

constant was 0.014 days-1. 

The decision to select point estimates for dose conversion parameters was done in this 

assessment with the acknowledgment that some of the variability around these parameters would 

be truncated. This loss was compensated for by using a pharmacokinetic uncertainty factor. 

Nevertheless, it did not seem prudent to select a point estimate, which is meant to reflect a 

population's central tendency, from one data set only. The two central tendency estimates of 

Swartout and Rice (2000) and Stern (1997) were very close in value (0.013 versus 0.014); the 

http://www.epa.gov/iris/subst/0073.htm
differences presumably resulted from the application of different distribution types. In this 

assessment the value of 0.014 days-1 was used for b in the dose conversion. 

Volume of blood in the body (V)

Stern (1997) cited three studies (Brown et al., 1962; Retzlaff et al., 1969; Huff and Feller, 1956) 

wherein correlation of body weight and blood volume were demonstrated. All studies were of U.S. 

women, presumably not pregnant at the time of the study. The mean blood volumes for each 

study were 3.58 L, 3.76 L, and 3.49 L, respectively; the mean of the combined data set is 3.61 L. 

If one assumes a 30% increase in blood volume with pregnancy, this would be 4.67 L. In their 

analysis, Swartout and Rice (2000) used data from a cohort of 20 pregnant Nigerian women 

(Harrison, 1966). Whole-blood volumes in the third trimester ranged from 4 to 6 L; the mean and 

median were both 5 L. Although 5 L is somewhat higher than the blood volume estimated from 

three studies of U.S. women, it is a reasonable value to use for V. 

Body weight (bw)

Swartout and Rice (2000) in their distributional analysis used the body weight data collected on 

the cohort of 20 pregnant Nigerian women (Harrison, 1966); this was the data set that they used 

for blood volume. Body weight during the third trimester of pregnancy ranged from 49.5 kg to 

73.9 kg, with a geometric mean of 55 kg. Stern (1997) used the Third National Health and 

Nutritional Survey (NHANES III) data for women 18 to 40 years old (NCHS, 1995). The mean 

weight was 66.6 kg and the 50th percentile value was 62.8 kg. The EPA Methodology for Deriving 

Ambient Water Quality Criteria for the Protection of Human Health (U.S. EPA, 2000) also cites 

NHANES III data; in the agency document, women of childbearing age were considered to be 

between the ages of 15 and 44 years old. The median body weight in this group was 63.2 kg and 

the mean was 67.3 kg. EPA also cites the earlier analyses of Ershow and Canter (1989); they do 

not state the age range but give a median of 64.4 kg and a mean of 65.8 kg. The 

recommendation in the EPA Methodology was to use a body weight value of 67 kg for a pregnant 

woman on the basis of the relatively current data from NHANES III. This value was used for body 

weight in the dose conversion. 

Dose conversion using the one-compartment model

d= (c x b x V)/(A x f x bw)

d= (BMDL05 μg/L x 0.014days-1 x 5L)/(0.95 x 0.059 x 67 kg)

BMD ANALYSIS OF THE FAROE ISLANDS STUDY 

The Faroe cohort was exposed to polychlorinated biphenyls (PCBs) as well as to methylmercury. 

An association was identified between PCB levels in cord tissue and four measures for which an 

effect of methylmercury also was identified (Grandjean et al., 1997). Analyses performed by the 

Faroe investigators indicate that the effects of methylmercury and PCBs are independent of each 

other (Budtz-Jørgensen et al., 1999a). Further, NRC presented an analysis of benchmark 

analyses designed to explore the influence of PCBs (Table 1). PCB measurements were made on 

cord tissue taken from about one-half of the Faroese cohort (about 450 children) and the 

"adjusted for PCBs" values are based on those children for whom PCB cord tissue levels and cordblood mercury levels were available. PCB-adjusted analyses also were conducted of children in 

the lowest tertile with respect to PCB levels, which reduced the number of children studied to 

about 150. No clear pattern arose from a comparison of the PCB-adjusted analyses and the 

http://www.epa.gov/iris/subst/0073.htm
original results. The observed variability probably was no more than that which would be 

expected to exist by chance alone. This analysis provides compelling evidence that the effects of 

methylmercury identified in this study are not the consequence of exposure to PCBs. 

BMD ANALYSIS OF ALL THREE EPIDEMIOLOGICAL STUDIES 

Benchmark dose analyses were performed for a number of endpoints from all three studies 

(Faroe Islands, Seychelles, New Zealand) (NRC, 2000, Chapter 7). NRC estimated a central 

tendency measure, equivalent to a BMD, across all three studies for all endpoints that were 

identified as significant in the Faroe Islands and New Zealand studies, and for all endpoints at 5.5 

years of age in the Seychelles study. They also determined a lower limit based on a theoretical 

distribution of BMDs, which is the logical equivalent of a BMDL. 

NRC also used a hierarchical random-effect model to reduce random variation in the estimate for 

these same endpoints from all three studies (NRC, 2000, Table 7-5, pp. 290-294). Additionally, 

this analysis was used in calculating BMD and BMDLs for the most sensitive and median endpoints 

from both the Faroe Islands and New Zealand studies (NRC, 2000, Table 7-6, p. 294). This 

approach also allowed an integrative analysis of data from all three studies. 

Table 1. BMD (BMDL) Estimates from the Faroe Islands Study with and without Adjustment for 

PCBs and in the Subset of Children Whose PCB Exposure Was Low (calculated using the K-power 

model) 

Exposure Endpointa

Full Cohort Adjusted for 

PCBs Low-PCB Tertile

BMD05

(BMDL05)

b BMD05 (BMDL05) BMD05 (BMDL05)

Maternalhair 

(ppm)

Finger 

tapping 20 (12) 17 (9) 7 (4)

CPT 

reaction 

time

18 (10) 27 (11) 13 (5)

BNT 15 (10) 24 (10) 21 (6)

CVLT: 

delayed 

recall

27 (14) 39 (12) 32 (7)

Cord 

blood 

(ppb)

Finger 

tapping 140 (79) 149 (66) 41 (24)

CPT 

reaction 

time

72 (46) 83 (49) 53 (28)

BNT 85 (58) 184 (71) 127 (40)

CVLT: 

delayed 

recall

246 (103) 224 (78) 393 (52)

a

CPT = Continuous Performance Test; BNT = Boston Naming Test; CVLT = California Verbal 

Learning Test.

http://www.epa.gov/iris/subst/0073.htm
b

BMDs are calculated under the assumption that 5% of the responses will be abnormal in 

unexposed subjects (P0 = 0.05), assuming a doubling of the excess risk (BMR = 0.05). 

Source: E. Budtz-Jørgensen, Copenhagen University, N. Keiding, Copenhagen University, and P. 

Grandjean,University of Southern Denmark, unpublished material, April 28, 2000, in Table 7-4, p. 

289, NRC 2000. 

Table 2 presents BMDL05s from a number of endpoints in terms of cord-blood mercury. These 

tests are all indications of neuropsychological processes involved in a child's ability to learn and 

process information. The BMDLs for these scores are all within a relatively close range. They were 

converted using a one-compartment model to an ingested dose of methylmercury that would 

result in the cord-blood level. The last column shows the corresponding RfD from application of a 

UF of 10 (see next section). The calculated RfD values converge at the same point: 0.1 

μg/kg/day. Among the endpoints from the Faroe Islands study were three deviations from 0.1 

μg/kg/day: 0.2 μg/kg/day for the CVLT entire cohort and 0.05 μg/kg/day for CPT and Finger 

Tapping, the lowest PCB tertile. EPA also calculated geometric means from the four endpoints 

from the Faroe Islands study; RfDs were 0.1 μg/kg/day based on these calculations. For the New 

Zealand study smoothed values, both the median value and the results of the McCarthy Perceived 

Performance test yielded RfDs of 0.05 μg/kg/day, and the McCarthy Motor Test yields an RfD of 

0.1 μg/kg/day. Based on the integrative analysis of all three studies, the RfD would be 0.1 

μg/kg/day 

Table 2. Comparison of BMDL05s and Corresponding RfDs from Faroes, New Zealand, and NRC 

Integrative Analysisa

Testb

BMDL05 ppb 

mercury 

cord

Ingested 

dose

μg;/kg/dayc

RfD 

μg/kg/dayd

BNT Faroes 

Whole cohort 58 1.081 0.1

PCB-adjusted 71 1.323 0.1

Lowest PCB 40 0.745 0.1

CPT Faroes

Whole cohort 46 0.857 0.1

PCB-adjusted 49 0.913 0.1

Lowest PCB 28 0.522 0.05

CVLT Faroes

Whole cohort 103 1.920 0.2

PCB-adjusted 78 1.454 0.1

Lowest PCB 52 0.969 0.1

Finger Tap Faroes

Whole cohort 79 1.472 0.1

PCB-adjusted 66 1.230 0.1

http://www.epa.gov/iris/subst/0073.htm
Lowest PCB 24 0.447 0.05

Geometric mean 

Faroes

Whole cohort 68 1.268 0.1

PCB-adjusted 65 1.212 0.1

Lowest PCB 34 0.634 0.1

Smoothed values

BNT Faroes 48 0.895 0.1

CPT Faroes 48 0.895 0.1

CVLT Faroes 60 1.118 0.1

Finger Tap Faroes 52 0.969 0.1

MCCPP New 

Zealand 28 0.522 0.05

MCMT New Zealand 32 0.596 0.1

Median values

Faroes 48 0.895 0.1

New Zealand 24 0.447 0.05

Integrative

All endpoints 32 0.596 0.1

a

BMDL05s from NRC (2000), Tables 7-4, 7-5, 7-6. Hair mercury was converted to blood mercury 

using a250:1 ratio (WHO, 1990) and an assumption of equivalent maternal and cord levels.

b

BNT = Boston Naming Test; CPT = Continuous Performance Test; CVLT = California Verbal 

Learning Test;MCCPP = McCarthy Perceived Performance; MCMT = McCarthy Motor Test.

c

 Calculated using a one-compartment model.

d

 Calculated using an UF of 10. 

Rather than choose a single measure for the RfD critical endpoint, EPA based this RfD for 

thisassessment on several scores from the Faroes measures, with supporting analyses from the 

New Zealandstudy, and the integrative analysis of all three studies.

__I.A.3. Uncertainty and Modifying Factors (Oral RfD)

UF = 10. 

MF = 1. 

In its report, NRC presented an analysis of the interindividual variability in the ingested dose of 

methylmercury corresponding to a given maternal-blood or hair-mercury concentration (NRC, 

2000, pp.83-95). NRC cited two analyses of the variability and uncertainty in the ingested dose 

estimates based on the one-compartment model (Stern, 1997; Swartout and Rice, 2000) as well 

as similar analysis of a PBPKmodel (Clewell et al., 1999). In general, all three analyses found 

similar ranges of variability due to pharmacokinetic factors. The ratios of estimated ingested 

http://www.epa.gov/iris/subst/0073.htm
doses at the 50th percentile/99th percentile ranged from 1.7 to 3.3. Using maternal blood as the 

starting point, the consolidated range from the three analyses is 1.7 to 3.0. 

Investigators have found that the placenta is not a barrier to the transfer of methylmercury from 

the mother to the developing fetus. Typically, a strong correlation exists between maternal-blood 

mercury concentrations and fetal-blood mercury concentrations, as shown by cord-blood. A 

review of the literature identified 21 studies that reported cord-blood mercury and maternal blood 

mercury data (Amin-Zaki et al., 1974; Baglan et al., 1974; Dennis and Fehr, 1975; Pitkin et al., 

1976; Kuhnert et al., 1981; Nishima et al., 1977; Lauwerys et al., 1978; Fujita and Takabatake, 

1977; Kuntz et al., 1982; Tsuchiya et al., 1984; Truska et al., 1989; Sikorski et al., 1989; 

Hansen et al., 1990; Soong et al.,1991; Soria et al., 1992; Ong et al., 1993; Akagi et al., 1997; 

Yang et al., 1997; Ramirez et al., 2000; Bjerregaard and Hansen, 2000; Vahter et al., 2000). 

Overall, data from these studies indicate that cord-blood mercury is higher than maternal blood 

mercury. The composite ratio from the studies reporting methylmercury concentrations indicates 

that the cord-blood: maternal blood ratio is around 1.7. These values are ratios of means and do 

not reflect the full range of variability in the individual mother-fetal pairs. Vahter et al. (2000) 

reported the 5th and 95th percentiles of cord:maternal Hg to be 0.88 and 3.1. Individual data 

were available from Fujita and Takabatake (1997); ratios calculated from these data ranged from 

0.78 to 4.36. 

EPA has chosen not to make a numerical adjustment between cord-blood and maternal-blood 

mercury. At this time the relationship between cord-blood and maternal-blood mercury is 

considered subject to variability and uncertainty, and is to be included in the determination of the 

uncertainty factor (UF). 

CHOICE OF UNCERTAINTY FACTOR

An RfD is based on human data, so an interspecies UF was not needed. The points of departure 

were the BMDL for a number of endpoints from the Faroe Islands study, with supporting analyses 

from the New Zealand study, and an integrative analysis of all three recent large epidemiological 

studies. RfDs derived from these BMDLs all converged on the same value; this convergence 

provides reassurance that additional UFs, other than for intraspecies variability, are not needed. 

Further, no issues were identified that indicated the need for a modifying factor (i.e., MF = 1). 

The two major phenomena included in the intraspecies UF for methylmercury were interindividual 

toxicokinetic variability in ingested dose estimation and pharmacodynamic variability and 

uncertainty. For the former, EPA relied in part on the NRC analyses of variability in the 

pharmacokinetic factors underlying the conversion of a biomarker level of methylmercury to an 

ingested daily dose of methylmercury that corresponds to that level. EPA chose not to make a 

numerical adjustment in the dose conversion for the potential differences between cord- and 

maternal-blood mercury levels, but rather toconsider them additional aspects of toxicokinetic 

variability and uncertainty. 

A quantitative uncertainty analysis of toxicodynamics was not possible. However, the population 

of the Faroe Islands is descended from Scandinavian stock that settled many generations ago, 

and is extremely homogeneous. The average toxicodynamic response of this population 

compared with that of the United States, which is genetically much more diverse, is unknown. 

Similarly, the relative variability of different populations also is unknown. A threefold UF for 

toxicodynamic variability and uncertainty was applied. 

In calculating the methylmercury RfD for this assessment, a composite UF of 10 was used. This 

choice was made to account for the following factors:

http://www.epa.gov/iris/subst/0073.htm
1. Pharmacokinetic variability and uncertainty in estimating an ingested mercury dose from 

cord-blood mercury concentration: a factor of 3 was applied.

2. Pharmacodynamic variability and uncertainty: a factor of 3 was applied.

Choosing an overall UF of 10 is supported by additional analyses of the Faroese 

neuropsychological data, wherein the observations made of the most highly exposed subgroup 

were excluded from the model (Grandjean et al., 1997). Associations remained significant when 

the part of the cohort with maternal-hair mercury concentrations greater than 10 ppm was 

excluded from the analyses. This finding indicates that it would be reasonable to expect some 

percentage of the population to show effects at or below 10 ppm hair mercury, or at levels at or 

below 40 ppb cord-blood. 

It is also important to note that no evidence of a threshold arose for methylmercury-related 

neurotoxicity within the range of exposures in the Faroe Islands study. This lack is indicated by 

the fact that, of the K power models, K = 1 provided a better fit for the endpoint models than did 

highervalues of K. 

ADDITIONAL IDENTIFIED DATA GAPS

Areas were identified that require additional research and/or analysis. 

Cardiovascular effects

There are two recently published studies show an association between low-level methylmercury 

exposure and cardiovascular effects. Sørensen et al. (1999) reported that in a study of 1,000 

7-year-old Faroese children, diastolic and systolic blood pressures increased by 13.9 and 14.6 

mm Hg, respectively, as the cord-blood mercury increased from 1 to 10 μg/L. They also reported 

a 47% decrease in heart rate variability (an indication of cardiac autonomic control) for the same 

increase in cord-blood mercury. Salonen et al. (1995) reported effects in adults from a study of 

1,833 Finnish men. Over the 7-year observation period, men with hair mercury in the highest 

tertile (2 ppm or higher) had a 2.0 times greater risk of acute myocardial infarction than the rest 

of the study population. 

Persistent and delayed neurotoxicity

Another area of concern is the onset or exacerbation of neurological deficits in aging populations 

previously exposed to methylmercury. In a follow-up study of the Minamata population, Kinjo et 

al. (1993) reported a high prevalence of sensory disturbance in people with Minamata disease 

(MD). Also evaluated were "acts of daily living" (ADL) that included the abilities to independently 

eat, bathe, wash, dress, and use the toilet. The prevalence of deficits was relatively greater in 

persons with MD compared with controls as a function of increasing age. In other words, 

exposure to methylmercury three decades earlier accelerated the aging process in aged 

individuals relative to younger ones. Fukuda et al. (1999) evaluated adults who lived in a 

methylmercury-polluted area near Minamata City in Japan's Kumamoto Prefecture but who were 

not designated MD patients; the authors then compared them with age-matched adults. 

Complaints that were significantly more frequent in methylmercury-contaminated areas included 

heart palpitation, dysesthesia, staggering when standing, resting and intention tremor in the 

hands, dizziness (especially when standing), low-tone tinnitus, low-pain sensation in hands and 

legs, and (among women only) loss of touch sensations in hands and legs. 

Animal studies lend support to the conclusion that methylmercury can have delayed effects that 

are uncovered with age. Spyker (1975) identified neurological and immune impairment in mice 

http://www.epa.gov/iris/subst/0073.htm
exposed prenatally to methylmercury as they approached 1 year of age. Rats exposed to 

methylmercury in utero through 16 days of age exhibited a decline in performance in a task that 

required a substantial motor output at an earlier age than did control rats (Newland and 

Rasmussen, 2000). Rice and colleagues (Rice, 1998, 1989; Rice and Hayward, 1999) identified 

accelerated aging of sensory system function in a series of studies in monkeys exposed during 

development to methylmercury. All of these observations are consistent with a hypothesis that 

either developmental or adult exposure to methylmercury can have adverse long-term sequelae 

that may not be detected for years or decades following cessation of exposure. However, these 

effects cannot be quantified based on available data. 

Reproductive effects

Short-term, high-dose studies in rodents and guinea pigs have reported low sperm counts, 

testicular tubule atrophy, reduced litter size, decreased fetal survival, resorptions, and fetal 

malformations following exposure to methylmercury (Khera, 1973; Lee and Han, 1995; Hughes 

and Annau, 1976; Fuyuta et al., 1978, 1979; Hirano et al., 1986; Mitsumori et al., 1990; Inouye 

and Kajiwara, 1988; Suter, 1975). No studies have been done of reproductive deficits in humans 

exposed to low-dose methylmercury, nor have there been any standard, two-generation 

reproductive studies. Bakir et al. (1973) noted a small number of pregnant women in the Iraqi 

population exposed to methylmercury in treated grain. Burbacher et al. (1988) reported 

decreased conception rates, early abortions, and stillbirths in monkeys treated with 

methylmercury, but at higher doses than those at which behavioral deficits were identified in the 

offspring. Rice (1996) also found no effect on time to pregnancy or viability of offspring at doses 

that produced neurotoxicity in the offspring. The available evidence therefore suggests that the 

developing nervous system is more sensitive to methylmercury than is reproductive competence. 

The database upon which this RfD is based is considered to be of high quality and extensive. The 

effects of methylmercury on other organ systems, such as the kidney and liver, are well 

documented and occur at higher exposures than the effects on the nervous system. Further, data 

from the most sensitive subpopulation for nervous system effects, the fetus, is the basis for this 

RfD. It is therefore considered that no additional UF(s) is warranted at this time. However, as 

additional data become available, they may be used in future RfD derivation. 

__I.A.4. Additional Studies/Comments (Oral RfD)

In a second Faroese cohort recruited from children born between 1994 and 1995 (Steurwald et 

al.,2000), decreases in neurologic optimality score (NOS) were associated with increasing cordblood mercury. This association remained statistically significant after adjustment for confounders 

(including cord and maternal serum PCB levels). There was an exposure-related decrease in NOS 

as cord-blood levels increased from less than 10 μg/L to greater than 40 μg/L. This finding 

indicates a dose-dependent effect at levels as low as (or lower than) those for which 

neuropsychological deficits were reported in the study of 7-year-old children (Grandjean et al., 

1997). The size of this study was relatively small (N = 182) and identified subtle changes at a 

very early developmental period, the clinical implications of which are less clear than the changes 

found in the study of 7-year-olds. 

The Marsh et al. (1987) study, chosen as the most appropriate one for determining the RfD 

derived by EPA for methylmercury in 1995 (U.S. EPA, 1995), reported clinical neurologic signs in 

81 mother-and-child pairs. Maternal-hair mercury concentrations were the exposure metric. 

Concentrations ranging from 1 to 674 ppm mercury were determined from X-ray fluorescent 

spectrometric analysis of selected regions of maternal scalp. These were correlated with clinical 

signs observed in the affected members of the mother-child pairs. The hair concentration for 

http://www.epa.gov/iris/subst/0073.htm
developmental effects was determined by application of a BMD approach. The analysts considered 

the combined incidence of all neurological effects in children exposed in utero. A Weibull model 

for extra risk was used to determine the BMD; in current terminology, this was a BMDL10 (95% 

lower confidence limit on the dose corresponding to a 10% risk level). This level was calculated to 

be 11 ppm mercury in maternal-hair (11 mg/kg hair). The BMD of 11 ppm maternal-hair mercury 

was converted to an exposure level of 44 μg mercury/L blood using a 250:1 ratio as described in 

the MSRC (U.S. EPA, 1997, pp. 6-22-6-23). 

It is informative to compare RfDs derived from animal studies with those derived from the 

epidemiological literature. RfDs derived from monkey studies are particularly relevant, as the 

neurotoxic effects produced by developmental methylmercury exposure in monkeys are similar to 

those identified in humans (Burbacher et al., 1990a; Gilbert and Grant-Webster, 1995). Studies 

at the University of Washington were of a relatively large cohort of macaque monkeys whose 

mothers were exposed throughout pregnancy to 50 μg/kg/day of methylmercury. The studies 

revealed deficits on cognitive tests during infancy, which may represent retarded development 

(Burbacher et al., 1986; Gunderson et al., 1986, 1988). These methylmercury-exposed monkeys 

also displayed aberrant play and social behavior (Burbacher et al., 1990b). Studies at the 

Canadian Health Protection Branch in the same species of monkey, dosed with 50 μg/kg/day from 

birth to 7 years of age, revealed visual, auditory, and somatosensory deficits, including evidence 

of delayed neurotoxicity identified in middle age (Rice and Gilbert, 1995, 1992, 1982; Rice, 

1989). Research in a cohort of monkeys dosed beginning in utero and continuing until 4 years of 

age revealed similar sensory system impairment (Rice and Hayward, 1999; Rice, 1998; Rice and 

Gilbert, 1995, 1990). Three individuals dosed at 10 or 25 μg/kg/day all exhibited impaired 

function in at least one sensory system in addition to evidence of delayed neurotoxicity (Rice, 

1998). In none of these studies was a NOAEL identified. Reference doses derived from these data 

would yield an RfD of 0.05 μg/kg/day from the in utero and postnatal exposure studies, and an 

RfD as low as 0.01 μg/kg/day based on combined in utero and postnatal exposure (Rice, 1996). 

The doses would be based on an UF of 10 to extrapolate from a LOAEL to a NOAEL and an UF of 

10 to extrapolate from animals to humans. Gilbert and Grant-Webster (1995) suggested an RfD 

of 0.025 μg/kg/day based on the same data. 

__I.A.5. Confidence in the Oral RfD

Study — High

Database — High

RfD — High

The overall confidence in this RfD assessment is high. Three high-quality epidemiological studies 

have been published since the last derivation of the oral RfD in 1995. Two of the studies (Faroe 

Islands, New Zealand) reported effects on a number of neuropsychological endpoints, whereas 

the third (Seychelles Islands) reported no effects related to in utero exposure to methylmercury. 

Benchmark dose analysis of a number of endpoints from both the New Zealand and Faroe Islands 

study converged on an RfD of 0.1 μg/kg-day, as did the integrative analysis combining all three 

studies. Although there was coexposure to PCBs in the Faroe Islands study, statistical analysis 

indicated that the effects of PCBs and methylmercury were independent. Moreover, benchmark 

dose analysis of the endpoints that were significantly associated with methylmercury yielded RfDs 

that were approximately the same when corrected for PCBs. The same was true when the 

analysis was or based on the subset of the cohort in the lowest tertile with respect to PCB levels, 

as compared with the full cohort. These findings provide further evidence that the identified 

effects are in fact the result of methylmercury exposure. 

http://www.epa.gov/iris/subst/0073.htm
The RfD used in this assessment report is the same as that derived in 1995 based on a study of a 

poisoning episode in Iraq. Experimental studies in monkeys also support the quantitative 

estimate of the RfD based on a NOAEL/LOAEL approach. Thus, there is a wealth of data from both 

epidemiological and experimental studies that converges on the derived RfD of 0.1 μg/kg/day. 

__I.A.6. EPA Documentation and Review of the Oral RfD

Source Document — U.S. EPA, 2001 

All reviewers' comments have been carefully evaluated and considered in the revision and 

finalization of this IRIS Summary. A record of these comments is summarized in the IRIS 

documentation files. To review, exit to the Summary and Response to the Peer Review for 

Methylmercury document (PDF). 

Other EPA Documentation — U.S. EPA, 1980, 1984, 1987, 1988, 1995

Consensus Date - 06/19/2001 

Screening-Level Literature Review Findings — A screening-level review conducted by an EPA 

contractor of the more recent toxicology literature pertinent to the RfD for Methylmercury 

conducted in September 2002 did not identify any critical new studies. IRIS users who know of 

important new studies may provide that information to the IRIS Hotline at hotline.iris@epa.gov or 

(202)566-1676.

__I.A.7. EPA Contacts (Oral RfD)

Please contact the IRIS Hotline for all questions concerning this assessment or IRIS, in general, 

at (202)566-1676 (phone), (202)566-1749 (FAX) or hotline.iris@epa.gov (internet address). 

_I.B. Reference Concentration for Chronic Inhalation Exposure (RfC)

Substance Name — Methylmercury (MeHg) 

CASRN — 22967-92-6

Not available at this time.

_II. Carcinogenicity Assessment for Lifetime Exposure

Substance Name — Methylmercury (MeHg) 

CASRN — 22967-92-6 

Last Revised — 05/01/1995

Section II provides information on three aspects of the carcinogenic assessment for the substance 

in question; the weight-of-evidence judgment of the likelihood that the substance is a human 

carcinogen, and quantitative estimates of risk from oral exposure and from inhalation exposure. 

The quantitative risk estimates are presented in three ways. The slope factor is the result of 

application of a low-dose extrapolation procedure and is presented as the risk per (mg/kg)/day. 

The unit risk is the quantitative estimate in terms of either risk per ug/L drinking water or risk per 

ug/cu.m air breathed. The third form in which risk is presented is a drinking water or air 

http://www.epa.gov/iris/subst/0073.htm
concentration providing cancer risks of 1 in 10,000, 1 in 100,000 or 1 in 1,000,000. The rationale 

and methods used to develop the carcinogenicity information in IRIS are described in The Risk 

Assessment Guidelines of 1986 (EPA/600/8-87/045) and in the IRIS Background Document. IRIS 

summaries developed since the publication of EPA's more recent Proposed Guidelines for 

Carcinogen Risk Assessment also utilize those Guidelines where indicated (Federal Register 61

(79):17960-18011, April 23, 1996). Users are referred to Section I of this IRIS file for 

information on long-term toxic effects other than carcinogenicity. 

_II.A. Evidence for Human Carcinogenicity

__II.A.1. Weight-of-Evidence Characterization

Classification — C; possible human carcinogen 

Basis — Based on inadequate data in humans and limited evidence of carcinogenicity in animals. 

Male ICR and B6C3F1 mice exposed to methylmercuric chloride in the diet had an increased 

incidence of renal adenomas, adenocarcinomas and carcinomas. The tumors were observed at a 

single site and in a single species and single sex. The renal epithelial cell hyperplasia and tumors 

were observed only in the presence of profound nephrotoxicity and were suggested to be a 

consequence of reparative changes in the cells. Several nonpositive cancer bioassays were also 

reported. Although genotoxicity test data suggest that methylmercury is capable of producing 

chromosomal and nuclear damage, there are also nonpositive genotoxicity data. 

__II.A.2. Human Carcinogenicity Data

Inadequate. Three studies were identified that examined the relationship between methylmercury 

exposure and cancer. No persuasive evidence of increased carcinogenicity attributable to 

methylmercury exposure was observed in any of the studies. Interpretation of these studies, 

however, was limited by poor study design and incomplete descriptions of methodology and/or 

results. 

Tamashiro et al. (1984) evaluated the causes of death in 334 subjects from the Kumamoto 

Prefecture who had been diagnosed with Minamata disease (methylmercury poisoning) and died 

between 1970 and 1980. The subjects involved fishermen and their families who had been 

diagnosed with the disease; thus, Minamata disease was used as a surrogate for methylmercury 

exposure. The controls were selected from all deaths that had occurred in the same city or town 

as the cases and were matched on the basis of sex, age at death (within 3 years) and year of 

death; two controls were matched to each subject. Malignant neoplasms were designated as the 

underlying cause of death in 14.7% (49/334) of the subjects and 20.1% (134/668) of the 

controls. For 47 subjects in which Minamata disease was listed as the underlying cause of death, 

the investigators reanalyzed the mortality data and selected one of the secondary causes to be 

the underlying cause of death in order to allow examination of the subjects and controls under 

similar conditions and parameters. The three subjects for which Minamata disease was listed as 

the only cause of death were excluded from further analysis. Using the Mantel-Haenzel method to 

estimate odds ratios, no significant differences were observed between the subjects and controls 

with respect to the proportion of deaths due to malignant neoplasms among males, females or 

both sexes combined. The estimated odds ratios and 95% confidence intervals were 0.84 

(0.49-1.43), 0.58 (0.28-1.21) and 0.75 (0.50-1.11) for males, females and both sexes combined. 

Similarly, no increases in odds ratio were observed among the subjects relative to the controls 

when malignant neoplasms were identified as a secondary cause of death or were listed on death 

certificates as one of the multiple causes of death. These data suggest that cancer incidence was 

not increased in persons with overt signs of methylmercury poisoning when compared with 

http://www.epa.gov/iris/subst/0073.htm
persons for whom no diagnosis of methylmercury poisoning had been made. Interpretation is 

limited by potential bias in designating the cause of death among patients with known Minamata 

disease and by the uncertainty regarding the extent of methylmercury exposure and undiagnosed 

Minamata disease among the controls. In a subsequent study, Tamashiro et al. (1986) compared 

the mortality patterns (between 1970 and 1981) among residents of the Fukuro and Tsukinoura 

districts in the Kumamoto Prefecture (inhabited mainly by fishermen and their families) with that 

of age-matched residents of Minamata City (also in the Kumamoto Prefecture) who died between 

1972 and 1978. In this study, high exposure to methylmercury was inferred from residence in a 

district believed to have higher intake of local seafood. By contrast, in the 1984 study described 

above, high methylmercury exposure was inferred from a diagnosis of Minamata disease. A total 

of 416 deaths were recorded in the Fukuro and Tsukinoura districts in 1970-1981, and 2325 

deaths were recorded in Minamata City in 1972-1978. No statistically significant increase in the 

overall cancer mortality rate was observed; however, an increase in the mortality rate due to 

liver cancer was observed (SMR, 207.3; 95% CI, 116.0-341.9). Analysis of mortality by sex 

showed a statistically significant increase in the rate of liver cancer only among males (SMR, 

250.5; 95% CI, 133.4-428.4). Males also had statistically significant higher mortality due to 

chronic liver disease and cirrhosis. The authors note that these results should be interpreted with 

caution because the population of the Fukuro and Tsukinoura districts had higher alcohol 

consumption and a higher prevalence of hepatitis B (a predisposing factor for hepatocellular 

cancer). Interpretation of these results is also limited by an incomplete description of the 

methodology used to calculate the SMRs; it is unclear whether the study authors used 

appropriate methods to compare mortality data collected over disparate time frames (12 years 

for exposed and 7 years for controls). 

In a study from Poland, Janicki et al. (1987) reported a statistically significant increase in 

mercury content of hair in leukemia patients (0.92 +/- 1.44 ppm [sic]; n=47) relative to that in 

healthy unrelated patients (0.49 +/- 0.41 ppm; n=79). Similarly, the mercury content in the hair 

of a subgroup of leukemia patients (0.69 +/- 0.75; n=19) was significantly greater than that in 

healthy relatives who had shared the same residence for at least 3 years preceding the onset of 

the disease (0.43 +/- 0.24 ppm; n=52). When patients with specific types of leukemia were 

compared with the healthy unrelated subjects (0.49 +/- 0.41 ppm; n=79), only those with acute 

leukemia (type not specified; 1.24 +/- 1.93 ppm; n=23) had a significantly increased hair 

mercury content. No significant differences in hair mercury content were observed in 9 patients 

with chronic granulocytic leukemia or 15 patients with chronic lymphocytic leukemia when 

compared with the unrelated, healthy controls. The authors inferred that acute leukemia was 

associated with increased level of mercury in hair. This study is of limited use for cancer risk 

assessment because of the following: uncertainty regarding the correlation between the 

chronology of incorporation of mercury in the hair and onset of the disease; the small population 

studied; the failure to describe adequately the characteristics of the leukemia patients or healthy 

controls (age distribution, length of residence in the region, criteria for inclusion in the study); 

uncertainty regarding the source of mercury exposure (the authors presumed that exposure was 

the result of use of methylmercury-containing fungicides); and the failure to address exposure to 

other chemicals or adjust for other leukemia risk factors. Furthermore, the variability of hair 

mercury content was large, and the mean hair mercury levels were within normal limits for all 

groups. Thus, the statistical significance may have been due to chance. 

The carcinogenic effects of organomercury seed dressing exposure were investigated in a series 

of case-control studies for incidence of soft-tissue sarcomas (Eriksson et al., 1981, 1990; Hardell 

and Eriksson, 1988) or malignant lymphomas (Hardell et al., 1981). These studies were 

conducted in Swedish populations exposed to phenoxyacetic acid herbicides or chlorophenols (the 

exposures of primary interest in the studies), organomercury seed dressings, or other pesticides. 

Exposure frequencies were derived from questionnaires and/or interviews. Control groups from 

http://www.epa.gov/iris/subst/0073.htm
the same region of the country were matched to cases based on vital status. A total of 402 cases 

of soft-tissue sarcoma and (among persons not exposed to phenoxyacetic acid herbicides) 128 

cases of malignant lymphoma were reported. In each study, the odds ratio for exposure to 

organomercury in seed dressings and the incidence of sarcoma or lymphoma was either <1.0 or 

the range of the 95% confidence interval for the odds ratio included 1.0; therefore, no 

association was indicated for organomercury exposure and soft-tissue sarcoma or malignant 

lymphoma. The study subjects were likely to have experienced exposures to the other pesticides 

and chemicals. 

__II.A.3. Animal Carcinogenicity Data

Limited. Three dietary studies in two strains of mice indicate that methylmercury is carcinogenic. 

Interpretation of two of the positive studies was complicated by observation of tumors only at 

doses that exceeded the MTD. A fourth dietary study in mice and four dietary studies in rats 

failed to indicate carcinogenicity associated with methylmercury exposure. Interpretation of four 

of the nonpositive studies was limited because of deficiencies in study design or failure to achieve 

an MTD. 

Methylmercuric chloride (>99% pure) was administered in the diet at levels of 0, 0.4, 2 or 10 

ppm (0, 0.03, 0.15 and 0.73 (mg/kg)/day in males and 0, 0.02, 0.11 and 0.6 (mg/kg)/day in 

females) to 60 ICR mice/sex/group for 104 weeks (Hirano et al., 1986). Interim sacrifices 

(6/sex/group) were conducted at 26, 52 and 78 weeks. Complete histopathological examinations 

were performed on all animals found dead, killed in extremis or killed by design. Mortality, group 

mean body weights and food consumption were comparable to controls. The first renal tumor was 

observed at 58 weeks in a high-dose male, and the incidence of renal epithelial tumors 

(adenomas or adenocarcinomas) was significantly increased in high-dose males (1/32, 0/25, 0/29 

and 13/26 in the control, low-, mid- and high-dose groups, respectively). Ten of the 13 tumors in 

high-dose males were adenocarcinomas. These tumors were described as solid type or cystic 

papillary types of adenocarcinomas. No invading proliferation into the surrounding tissues was 

observed. The incidence of renal epithelial adenomas was not significantly increased in males, 

and no renal adenomas or adenocarcinomas were observed in any females studied. Focal 

hyperplasia of the tubular epithelium was reported to be increased in high-dose males (13/59; 

other incidences not reported). Increases in non-neoplastic lesions in high- dose animals provided 

evidence that an MTD was exceeded. Non-neoplastic lesions reported as increased in treated 

males included the following: epithelial degeneration of the renal proximal tubules; cystic kidney; 

urinary cast and pelvic dilatation; and decreased spermatogenesis. Epithelial degeneration of the 

renal proximal tubules and degeneration or fibrosis of the sciatic nerve was reported in high-dose 

females. 

Methylmercuric chloride (>99% pure) was administered in the diet at levels of 0, 0.4, 2 or 10 

ppm (0, 0.3, 0.14 and 0.69 (mg/kg)/day in males and 0, 0.03, 0.13 and 0.60 (mg/kg)/day in 

females) to 60 B6C3F1 mice/sex/group for 104 weeks (Mitsumori et al., 1990). In high-dose 

males, a marked increase in mortality was observed after week 60 (data presented graphically; 

statistical analyses not performed by authors). Survival at study termination was approximately 

50, 60, 60 and 20% in control, low-, mid- and high-dose males, respectively, and 58, 68, 60 and 

60% in control, low-, mid- and high-dose females, respectively. The cause of the high mortality 

was not reported. At study termination, the mean body weight in high-dose males was 

approximately 67% of controls and in high-dose females was approximately 90% of controls 

(data presented graphically; statistical analyses not performed by study authors). The incidence 

of focal hyperplasia of the renal tubules was significantly increased in high-dose males (14/60; 

the incidence was 0/60 in all other groups). The incidence of renal epithelial carcinomas 

(classified as solid or cystic papillary type) was also significantly increased in high- dose males 

http://www.epa.gov/iris/subst/0073.htm
(13/60; the incidence was 0/60 in all other groups). The incidence of renal adenomas (classified 

as solid or tubular type) was also significantly increased in high-dose males; the incidence was 

0/60, 0/60, 1/60 and 5/60 in control, low-, mid- and high-dose males, respectively, and 0/60, 

0/60, 0/60 and 1/60 in control low-, mid- and high-dose females, respectively. No metastases 

were seen in the animals. The incidences of a variety of non- neoplastic lesions were increased in 

the high-dose mice including the following: sensory neuropathy; neuronal necrosis in the 

cerebrum; neuronal degeneration in the cerebellum; and chronic nephropathy of the kidney. 

Males exhibited tubular atrophy of the testis (1/60, 5/60, 2/60 and 54/60 in control, low-, midand high-dose, respectively) and ulceration of the glandular stomach (1/60, 1/60, 0/60 and 7/60 

in control, low-, mid- and high- dose males, respectively). An MTD was achieved in mid-dose 

males and high- dose females. High mortality in high-dose males indicated that the MTD was 

exceeded in this group. 

Mitsumori et al. (1981) administered 0, 15 or 30 ppm of methylmercuric chloride (>99% pure) in 

the diet (0, 1.6 and 3.1 (mg/kg)/day) to 60 ICR mice/sex/group for 78 weeks. Interim sacrifices 

of up to 6/sex/group were conducted at weeks 26 and 52. Kidneys were microscopically 

examined from all animals that died or became moribund after week 53 or were killed at study 

termination. Lungs from mice with renal masses and renal lymph nodes showing gross 

abnormalities were also examined. Survival was decreased in a dose- related manner; at week 78 

survival was 40, 10 and 0% in control, low- and high-dose males, respectively, and 55, 30 and 

0%, in control, low- and high- dose females, respectively (statistical analyses not performed). 

The majority of high-dose mice (85% males and 98% females) died by week 26 of the study. 

Examination of the kidneys of mice that died or were sacrificed after 53 weeks showed a 

significant increase in renal tumors in low-dose males (13/16 versus 1/37 in controls). The 

incidence of renal epithelial adenocarcinomas in control and low-dose males was 0/37 and 11/16, 

respectively. The incidence of renal epithelial adenomas in control and low-dose males was 1/37 

and 5/16, respectively. No renal tumors were observed in females in any group. No metastases 

to the lung or renal lymph nodes were observed. Evidence of neurotoxicity and renal pathology 

were observed in the treated mice at both dose levels. The high mortality in both groups of 

treated males and in high- dose females indicated that the MTD was exceeded in these groups. 

(Note: Hirano et al. (1986) was a followup to this study.) 

Mitsumori et al. (1983, 1984) administered diets containing 0, 0.4, 2 or 10 ppm of 

methylmercuric chloride (0, 0.011, 0.05 and 0.28 (mg/kg)/day in males; 0, 0.014, 0.064 and 

0.34 (mg/kg)/day in females) to 56/sex/group Sprague-Dawley rats for up to 130 weeks. Interim 

sacrifices of 10/group (either sex) were conducted at weeks 13 and 26 and of 6/group (either 

sex) at weeks 52 and 78. Mortality was increased in high-dose males and females. At week 104, 

survival was approximately 55, 45, 75 and 10% in control, low-, mid- and high-dose males, 

respectively, and 70, 75, 75 and 30% in control, low-, mid- and high-dose females, respectively 

(data presented graphically). All males in the high-dose group had died by week 119. Body 

weight gain was significantly decreased in high-dose males starting after week 44 and females 

after 44 weeks (approximately 10-20%, data presented graphically). No increase in tumor 

incidence was observed in either males or females. Noncarcinogenic lesions that were 

significantly increased in high-dose rats included the following: degeneration in peripheral nerves 

and the spinal cord (both sexes); degeneration of the proximal tubular epithelium (both sexes); 

severe chronic nephropathy (females); parathyroid hyperplasia (both sexes); polyarteritis nodosa 

and calcification of arterial wall (females); fibrosis of bone (females); bile duct hyperplasia 

(males); and hemosiderosis and extramedullary hematopoiesis in the spleen (males). Mid-dose 

males exhibited significantly increased degeneration of the proximal tubular epithelium and 

hyperplasia of the parathyroid. An MTD was achieved in mid-dose males and exceeded in highdose males and high-dose females. 

http://www.epa.gov/iris/subst/0073.htm
No tumor data were reported in a study using Wistar rats (Munro et al., 1980). Groups of 50 

Wistar rats/sex/dose were fed diets containing methylmercury; doses of 2, 10, 50 and 250 

(ug/kg)/day were fed for 26 months. High-dose female rats exhibited reduced body weight gains 

and showed minimal clinical signs of neurotoxicity; however, high-dose male rats showed overt 

clinical signs of neurotoxicity, decreased hemoglobin and hematocrit values, reduced weight gains 

and significantly increased mortality. Histopathologic examination of the high-dose rats of both 

sexes revealed demyelination of dorsal nerve roots and peripheral nerves. Males showed severe 

dose-related kidney damage, and females had minimal renal damage. 

No increase in tumor incidence or decrease in tumor latency was observed in another study using 

rats of an unspecified strain (Verschuuren et al., 1976). Groups of 25 female and 25 male rats 

were administered methylmercuric chloride at dietary levels of 0, 0.1, 0.5 and 2.5 ppm (0, 0.004, 

0.02 and 0.1 (mg/kg)/day) for 2 years. No significant effects were observed on growth or food 

intake except for a 6% decrease (statistically significant) in body weight gain at 60 weeks in 

high-dose females. Survival was 72, 68, 48 and 48% in control, low-, mid- and high-dose males, 

respectively, and 76, 60, 64 and 56% in control, low-, mid- and high-dose females, respectively 

(statistical significance not reported). Increases in relative kidney weights were observed in both 

males and females at the highest dose. No effects on the nature or incidence of pathological 

lesions were observed, and tumors were reported to have been observed with comparable 

incidence and latency among all of the groups. This study was limited by the small sample size. 

No increase in tumor incidence was observed in a study using white Swiss mice (Schroeder and 

Mitchener, 1975). Groups of mice (54/sex/group) were exposed until death to methylmercuric 

acetate in the drinking water at two doses. The low-dose group received 1 ppm methylmercuric 

acetate (0.19 (mg/kg)/day). The high-dose group received 5 ppm methylmercuric acetate (0.95 

(mg/kg)/day) for the first 70 days and then 1 ppm thereafter, due to high mortality (21/54 males 

and 23/54 females died prior to the dose reduction). Survival among the remaining mice was not 

significantly different from controls. Significant reductions in body weight were reported in highdose males (9-15% lower than controls) and high-dose females (15-22% lower than controls) 

between 2 and 6 months of age. After dying, mice were weighed and dissected; gross tumors 

were counted, and limited histopathologic sections were made of heart, lung, liver, kidney and 

spleen for microscopic examination. This study is limited because complete histological 

examinations were not performed. 

No increase in tumor incidence was observed in a multiple-generation reproduction study using 

Sprague-Dawley rats (Newberne et al., 1972). Groups of rats (30/sex) were given semisynthetic 

diets supplemented with either casein or a fish protein concentrate to yield dietary levels of 0.2 

ppm methylmercury (0.008 (mg/kg)/day). Another group of controls received untreated rat 

chow. Rats that received diets containing methylmercury during the 2-year study had body 

weights and hematology comparable to controls. Detailed histopathological analyses revealed no 

lesions of the brain, liver, or kidney that were attributable to methylmercury exposure. Mortality 

data were not presented. Interpretation of these data is limited by the somewhat small group 

sizes and failure to achieve an MTD. 

__II.A.4. Supporting Data for Carcinogenicity 

Blakley (1984) administered methylmercuric chloride to female Swiss mice (number/group not 

specified) in drinking water at concentrations of 0, 0.2, 0.5 or 2.0 mg/L for 15 weeks 

(approximately 0, 0.03, 0.07 and 0.27 (mg Hg/kg)/day). At the end of week 3, a single dose of 

1.5 mg/kg of urethane was administered intraperitoneally to 16-20 mice/group. No effects on 

weight gain or food consumption were observed. Lung tumor incidence in mice not administered 

urethane (number/group not specified) was less than one tumor/mouse in all groups. Statistically 

http://www.epa.gov/iris/subst/0073.htm
significant trends for increases in the number and size of lung adenomas/mouse with increasing 

methylmercury dose were observed; the number of tumors/mouse was 21.5, 19.4, 19.4 and 33.1 

in control, low-, mid- and high-dose mice, respectively, and the tumor size/mouse was 0.70, 

0.73, 0.76 and 0.76 mm in control, low-, mid- and high-dose mice, respectively. The study 

authors suggest that the increase in tumor number and size may have been related to the 

immunosuppressive activity of methylmercury. It should be noted that this study is considered a 

short-term bioassay, and pulmonary adenomas were the only tumor type evaluated. 

Humans ingesting methylmercury-contaminated foods have been reported to experience 

chromosomal aberrations (Skerfving et al., 1970, 1974) or SCE (Wulf et al., 1986); however, 

interpretation of these studies is limited by methodological deficiencies. 

As reviewed in WHO (1990), methylmercury is not a potent mutagen but appears to be capable 

of causing chromosome damage and nuclear perturbations in a variety of systems. In Bacillus 

subtilis, methylmercury produced DNA damage (Kanematsu et al., 1980). Methylmercury 

produced chromosomal aberrations and aneuploidy in human peripheral lymphocytes (Betti et al., 

1992), SCE in human lymphocytes (Morimoto et al., 1982), and DNA damage in human nerve 

and lung cells as well as Chinese hamster V-79 cells and rat glioblastoma cells (Costa et al., 

1991). 

Bone marrow cells of cats treated with methylmercury in a study by Charbonneau et al. (1976) 

were examined by Miller et al. (1979). The methylmercury treatment resulted in an increased 

number of nuclear abnormalities and an inhibition of DNA repair capacity. Methylmercury induced 

a weak mutagenic response in Chinese hamster V-79 cells (Fiskesjo, 1979). Methylmercury also 

induced histone protein perturbations and influenced factors regulating nucleolus-organizing 

activity (WHO, 1990). Moreover, methylmercury has been reported to interfere with gene 

expression in cultures of glioma cells (WHO, 1990). Mailhes (1983) reported a significant increase 

in the number of hyperploid oocysts in Lak:LVG Syrian hamsters fed methyl mercury; however, 

no evidence of chromosomal damage was reported. Suter (1975) concluded that strain-specific 

differences exist with respect to the ability of methylmercury to produce dominant lethal effects 

in mice. Nondisjunction and sex-linked recessive lethal mutations were observed in Drosophila 

melanogaster treated with methylmercury (Ramel, 1972 as cited in U.S. EPA, 1985). 

Methylmercury produced single strand breaks in DNA in cultured L5178Y cells (Nakazawa et al., 

1975). 

Negative studies have also been reported. Methylmercury acetate was reported to be negative in 

a Salmonella typhimurium assay and a mouse micronucleus assay (Heddle and Bruce, 1977, as 

reported in Jenssen and Ramel, 1980). Methylmercury was not mutagenic and did not cause 

recombination in Saccharomyces cerevisiae but did slightly increase chromosomal nondisjunction 

(Nakai and Machida, 1973). Matsumoto and Spindle (1982) reported no significant increase in 

SCE in developing mouse embryos; they did report, however, that the developing mouse 

embryos were highly sensitive to in vitro treatment with methylmercury. 

_II.B. Quantitative Estimate of Carcinogenic Risk from Oral Exposure

None. The two studies by Mitsumori et al. (1981, 1990) were limited by high mortality in the 

high-dose males, the only group to exhibit a statistically significant increase in tumor incidence. 

Tumors were observed only in those dose groups in which the MTD had been exceeded. The 

study by Hirano et al. (1986) was not limited by low survival, but the tumors were observed in 

conjunction with nephrotoxicity and, thus, their incidence may have been a high-dose 

phenomenon that would not be expected to occur at low doses. The tumors appeared to originate 

http://www.epa.gov/iris/subst/0073.htm
from focal hyperplasia of the tubular epithelium induced as a reparative change. The hyperplasia 

was not observed in tubular epithelium that was undergoing early degenerative changes. Thus, 

the tumors may not occur where degenerative changes do not occur. The genotoxicity data 

indicate that methylmercury is not a potent mutagen but may produce chromosomal damage; 

these data do not support a hypothesis that methylmercury is a genotoxic carcinogen. It appears, 

rather, that methylmercury exerts its carcinogenic effect only at high dose, at or above an MTD. 

Because the linearized multistage procedure is based on the assumption of linearity at low doses, 

the relevance of deriving a slope factor based on data for which a threshold may exist is 

questionable. 

It is likely that systemic non-cancer effects would be seen at methylmercury exposures lower 

than those required for tumor formation. Long- term administration of methylmercury to 

experimental animals produces overt symptoms of neurotoxicity at daily doses an order of 

magnitude lower than those required to induce tumors in mice. 

_II.C. Quantitative Estimate of Carcinogenic Risk from Inhalation Exposure

None.

_II.D. EPA Documentation, Review, and Contacts (Carcinogenicity Assessment)

__II.D.1. EPA Documentation

Source Documents -- U.S. EPA, 1995 

This IRIS Summary is included in The Mercury Study Report to Congress which was reviewed by 

OHEA and EPA's Mercury Work Group in November 1994. An Interagency Review by scientists 

from other federal agencies took place in January 1995. The report was also reviewed by a panel 

of non-federal external scientists in January 1995 who met in a public meeting on January 25-26. 

All reviewers comments have been carefully evaluated and considered in the revision and 

finalization of this IRIS summary. A record of these comments is summarized in the IRIS 

documentation files. 

__II.D.2. EPA Review (Carcinogenicity Assessment)

Agency Work Group Review — 03/03/1994 

Verification Date — 03/03/1994

Screening-Level Literature Review Findings — A screening-level review conducted by an EPA 

contractor of the more recent toxicology literature pertinent to the cancer assessment for 

Methylmercury conducted in September 2002 did not identify any critical new studies. IRIS users 

who know of important new studies may provide that information to the IRIS Hotline at 

hotline.iris@epa.gov or (202)566-1676.

__II.D.3. EPA Contacts (Carcinogenicity Assessment)

Please contact the IRIS Hotline for all questions concerning this assessment or IRIS, in general, 

at (202)566-1676 (phone), (202)566-1749 (FAX) or hotline.iris@epa.gov (internet address).

http://www.epa.gov/iris/subst/0073.htm
_III. [reserved]

_IV. [reserved] 

_V. [reserved]

_VI. Bibliography 

Substance Name — Methylmercury (MeHg) 

CASRN — 22967-92-6 

Last Revised — 07/27/2001

_VI.A. Oral RfD References

Aberg, B; Ekman, L; Falk, R; et al. (1969) Metabolism of methyl mercury (203Hg) compounds in 

man. Arch Environ Health 19:478-484. 

Akagi-H, I; Kanoka; Kaneko, K. (1997) J Jpn Soc Obstet Gynecol Neonat Hematol 7(2):S112-

S113. 

Al-Shahristani, H; Shihab, KM. (1974) Variation of biological half-life of methyl mercury in man. 

Arch Environ Health 28:342-344. 

Amin-Zaki, L; Elhassani, S; Majeed, MA; et al. (1974) Intra-uterine methylmercury poisoning in 

Iraq. Pediatrics 54:587-595. 

Baglan RJ; Brill, AB; Schulert, A; et al. (1974) Utility of placental tissue as an indicator of trace 

element exposure to adult and fetus. Environ Res 8:64-70. 

Bakir, F; Damluji, S; Amin-Zaki, L; et al. (1973) Methylmercury poisoning in Iraq. Science 

181:230-241. 

Berglund, F; Berlin, M; Birke, G; et al. (1971) Methyl mercury in fish: a toxicologic- epidemiologic 

evaluation of risks. Report from an expert group. Nordisk Hygienisk Tidskrift, Stockholm Suppl. 

4:19-364. 

Bjerregaard P; Hansen, JC. (2000) Organochlorines and heavy metals in pregnant women from 

the Disko Bay area in Greenland. Sci Total Environ 17:245(1-3):195-202. 

Brown, E; Hopper, J; Hodges, JL Jr; et al. (1962) Red cell, plasma, and blood volume in healthy 

women measured by radiochromium cell-labeling and hematocrit. J Clin Invest 41:2182-2190. 

Budtz-Jørgensen, E; Keiding, N; Grandjean, P; et al. (1999a) Methylmercury neurotoxicity 

independent of PCB exposure. [Letter]. Environ Health Perspect 107(5):A236-237. 

Budtz-Jørgensen, E; Keiding, N; Grandjean, P. (1999b) Benchmark modeling of the Faroese 

methylmercury data. Final Report to U.S. EPA. Research Report 99/5. Department of Biostatistics, 

University of Copenhagen. 

Budtz-Jørgensen, E; Grandjean, P; Keiding, N; et al. (2000) Benchmark dose calculations of 

methylmercury-associated neurobehavioral deficits. Toxicol Lett 112-113:193-199. 

http://www.epa.gov/iris/subst/0073.htm
Burbacher, TM; Grant, KS; Mottet, NK. (1986). Retarded object permanence development in 

methylmercury exposed Macaca fascicularis infants. Dev Psychobiol 22:771-776. 

Burbacher, TM; Mohamed, MK; Mottett, NK. (1988) Methyl mercury effects on reproduction and 

offspring size at birth. Reprod Toxicol 1:267-278. 

Burbacher, TM; Rodier, PM; Weiss, B. (1990a) Methylmercury developmental neurotoxicity: a 

comparison of the effects in humans and animals. Neurotoxicol Teratol 12:191-202. 

Burbacher, TM; Sackett, GP; Mottet, NK. (1990b) Methylmercury effects on the social behavior of 

Macaca fascicularis infants. Neurotoxicol Teratol 12:65-71. 

Clewell, HJ; Gearhart, JM; Gentry, PR; et al. (1999) Evaluation of the uncertainty in an oral 

reference dose for methylmercury due to interindividual variability in pharmacokinetics. Risk Anal 

19:547-558. 

Davidson, P; Myers, G; Cox, C; et al. (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. 

Davidson, PW; Myers, GJ; Cox, C; et al. (1998) Effects of prenatal and postnatal methylmercury 

exposure from fish consumption on neurodevelopment: outcomes at 66 months of age in the 

Seychelles child development study. JAMA 280:701-707. 

Dennis, CA; Fehr F. (1975) The relationship between mercury levels in maternal and cord-blood. 

Sci Total Environ 3(3):275-277. 

Ershow, AG; Canter, KP. (1989) Total water and tapwater intake in the United States: populationbased estimates of quantities and sources. Life Sciences Research Office, Federation of American 

Societies for Experimental Biology, Bethesda, MD. (Prepared under NCI #263-MD-810264.) 

Fujita, M; Takabatake, E. (1977) Mercury levels in human maternal and neonatal blood, hair and 

milk. Bull Environ Contam Toxicol 18(2):205-209. 

Fukuda, Y; Ushijima, K; Kitano, T. (1999) An analysis of subjective complaints in a population 

living in a methylmercury-polluted area. Environ Res 81:100-107. 

Fuyuta, M; Fujimoto, T; Hirata, S. (1978) Embryotoxic effects of methylmercuric chloride 

administered to mice and rats during organogenesis. Teratology 18(3):353-366. 

Fuyuta, M; Fujimoto, T; Kiyofuji, E. (1979) Teratogenic effects of a single oral administration of 

methylmercuric chloride in mice. Acta Anat (Basel) 104(3):356-362. 

Gilbert, SG; Grant-Webster, KS. (1995) Neurobehavioral effects of developmental methylmercury 

exposure. Environ Health Perspect 103 Suppl. 6:135-142. 

Ginsberg, GL; Toal, BF. (2000) Development of a single-meal fish consumption advisory for 

methylmercury. Risk Anal 20:41-47. 

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. 

http://www.epa.gov/iris/subst/0073.htm
Gunderson, VM; Grant, KS; Fagan, JF. (1986) The effect of low-level prenatal methylmercury 

exposure on visual recognition memory of infant crab-eating macaques. Child Dev 57:1076-1083. 

Gunderson, VM; Grant-Webster, KS; Burbacher, TM; et al. (1988) Visual recognition memory 

deficits in methylmercury-exposed Macaca fascicularis infants. Neurotoxicol Teratol 10:373-379. 

Hansen, JE; Tarp, U; Bohm, J. (1990) Prenatal exposure to methyl mercury among Greenlandic 

Polar Inuits. Arch Environ Health 45:355-358. 

Harrison, KA. (1966) Blood volume changes in normal pregnant Nigerian women. J Obstet Gynaec 

Br Cwlth 73:717-723. 

Hirano, M; Mitsumori, K; Maita, K; et al. (1986). Further carcinogenicity study on methylmercury 

chloride in ICR mice. Nipon Juigaku Zasshi (Jpn J Vet Sci) 48(1):127-135. 

Huff, RL; Feller, DD. (1956) Relation of circulating red cell volume to body density and obesity. J 

Clin Invest 35:1-10. 

Hughes, JA; Annau, Z. (1976) Postnatal behavioral effects in mice after prenatal exposure to 

methylmercury. Pharmacol Biochem Behav 4(4):385-391. 

Inouye, M; Kajiwara, Y. (1988). Developmental disturbances of the fetal brain in guinea pigs 

caused by methylmercury. Arch Toxicol 62(1):15-21. 

Kershaw, TG; Clarkson, TW; Dhahir, PH. (1980) The relationship between blood levels and the 

dose of methylmercury in man. Arch Environ Health 35(1):28-36. 

Khera, KS. (1973) Reproductive capability of male rats and mice treated with methylmercury. 

Toxicol Appl Pharmacol 24(2):167-177. 

Kinjo, Y; Higashi, H; Nakano, A; et al. (1993) Profile of subjective complaints and activities of 

daily living among current patients with Minamata disease after 3 decades. Environ Res 63

(2):241-251. 

Kjellstrom, T; Kennedy, P; Wallis, S; et al. (1986) Physical and mental development of children 

with prenatal exposure to mercury from fish. Stage 1: Preliminary test at age 4. Natl Swed 

Environ Protec Bd, Rpt 3080 (Solna, Sweden). 

Kjellstrom, T; Kennedy, P; Wallis, S; et al. (1989) Physical and mental development of children 

with prenatal exposure to mercury from fish. Stage 2: Interviews and psychological tests at age 

6. Natl Swed Environ Prot Bd, Rpt 3642 (Solna, Sweden). 

Kuntz, WD; Pitkin, RM; Bostrom, A; et al. (1982) Maternal and cord-blood background mercury 

levels: a longitudinal surveillance. Am J Obstet Gynecol 143:440-443. 

Kuhnert, PM; Kuhnert, BR; Erhard, P (1981) Comparison of mercury levels in maternal-blood, 

fetal cord-blood, and placental tissues. Am J Obstet Gynecol. 139(2):209-213. 

Lauwerys, R; Buchet, JP; Roels, H; et al. (1978) Placental transfer of lead, mercury, cadmium, 

and carbon monoxide in women. I. Comparison of the frequency distributions of the biological 

indices in maternal and umbilical cord-blood. Environ Res 15(2):278-289. 

http://www.epa.gov/iris/subst/0073.htm
Lee, JH; Han, DH. (1995). Maternal and fetal toxicity of methylmercuric chloride administered to 

pregnant Fischer 344 rats. J Toxicol Environ Health 45(4):415-425. 

Marsh, DO; Clarkson, TW; Cox, C; et al. (1987) Fetal methylmercury poisoning: relationship 

between concentration in single strands of maternal-hair and child effects. Arch Neurol 44:1017-

1022. 

Miettinen, JK; Rahola, T; Hattula, T; et al. (1971). Elimination of 203-Hg methylmercury in man. 

Ann Clin Res 3:116-122. 

Mitsumori, K; Hiarano, M; Ueda, H; et al. (1990) Chronic toxicity and carcinogenicity of 

methylmercury chloride in B6C3F1 mice. Fundam Appl Toxicol 14:179-190. 

Myers, GJ; Marsh, DO; Cox, C; et al. (1995a) A pilot neurodevelopmental study of Seychellois 

children following in utero exposure to methylmercury from a maternal fish diet. Neurotoxicology 

16(4):629-638. 

Myers, GJ; Marsh, DO; Davidson, PW. (1995b) Main neurodevelopmental study of Seychellois 

children following in utero exposure to methylmercury from a maternal fish diet: outcome at six 

months. Neurotoxicology 16(4):653-664. 

Myers, GJ; Davidson, PW; Cox, C; et al. (1995c) Neurodevelopmetnal outcomes of Seychellois 

children sixty-six months after in utero exposure to methylmercury from a maternal fish diet: 

pilot study. Neurotoxicology 16(4):639-652. 

Myers, GJ; Davidson, PW; Shamlaye, CF; et al. (1997) Effects of prenatal methylmercury 

exposure from a high fish diet on developmental milestones in the Seychelles Child Development 

Study. Neurotoxicology 18(3):819-830. 

National Center for Health Statistics (NCHS). (1995) [Section 4.2.3, body weight]. 

Newland, CM; Rasmussen, EB. (2000) Aging unmasks adverse effects of gestational exposure to 

methylmercury in rats. Neurotoxicol Teratol 22. 

Nishima, T; Ikeda, S; Tada, T; et al. (1977) Mercury content levels in mother and newborn and 

their interrelation. Ann Rep Tokyo Metro Res Lab PH 28:215-220. 

National Research Council (NRC). (2000) Toxicological effects of methylmercury. Committee on 

the Toxicological Effects of Methylmercury, Board on Environmental Studies and Toxicology, 

Commission on Life Sciences, National Research Council. Washington, DC: National Academy 

Press. 

Ong, CN; Chia, SE; Foo, SC; et al. (1993) Concentrations of heavy metals in maternal and 

umbilical cord-blood. Biometals 6:61-66. 

Pitkin, RM; Bahns, JA; Filer, LJ, Jr; et al. (1976) Mercury in human maternal and cord-blood, 

placenta, and milk. Proc Soc Exp Biol Med 151(3):565-567. 

Ramirez, GB; Cruz, MCV; Pagulayan, O; et al. (2000) The Tagum Study: I. Analysis and clinical 

correlates of mercury in maternal and cord-blood, breast milk, meconium, and infants' hair. 

Pediatrics 106:774-781. 

http://www.epa.gov/iris/subst/0073.htm
Retzlaff, JA; Tauxe, WN; Khely, JM; et al. (1969) Erythrocyte volume, plasma volume, and lean 

body mass in adult men and women. Blood 33:649-664. 

Rice, DC. (1989) Delayed neurotoxicity in monkeys exposed developmentally to methylmercury. 

Neurotox 10:645-650. 

Rice, DC. (1996) Sensory and cognitive effects of developmental methylmercury exposure in 

monkeys, and a comparison to effects in rodents. Neurotoxicology 17:139-154. 

Rice, DC. (1998) Age-related increase in auditory impairment in monkeys exposed in utero plus 

postnatally to methylmercury. Toxicol Sci 44(2):191-196. 

Rice, DC; Gilbert, SG. (1982) Early chronic low-level methylmercury poisoning in monkeys 

impairs spatial vision. Science 216:759-761. 

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. 

Rice, DC; Gilbert, SG. (1992) Exposure to methylmercury from birth to adulthood impairs highfrequency hearing in monkeys. Toxicol Appl Pharmacol 102:151-163. 

Rice, DC; Gilbert, SG. (1995) Effects of developmental methylmercury exposure or lifetime lead 

exposure on vibration sensitivity function in monkeys. Toxicol Appl Pharmacol 134(1):161-169. 

Rice, DC; Hayward, S. (1999) Comparison of visual function at adulthood and during aging in 

monkeys exposed to lead or methylmercury. Neurotoxicology 20:767-784. 

Salonen, JT; Seppanen, K; Nyyssonen, K; et al. (1995) Intake of mercury from fish, lipid 

peroxidation, and the risk of myocardial infarction and coronary, cardiovascular, and any death in 

Eastern Finnish men. Circulation 91(3):645-655. 

Sherlock, JC; Lindsay, DG; Hislop, J; et al. (1982) Duplication diet study on mercury intake by 

fish consumers in the United Kingdom. Arch Environ Health 37(5):271-278. 

Sherlock, J; Hislop, J; Newton, D; et al. (1984) Elevation of mercury in human blood from 

controlled chronic ingestion of methylmercury in fish. Hum Toxicol 3:117-131. 

Sikorski, R; Paszkowski, T; Slawinski, P; (1989) The intrapartum content of toxic metals in 

maternal-blood and umbilical cord-blood. Ginekol Pol 60(3):151-155. 

Smith, JC; Allen, PV; Turner, MD; et al. (1994) The kinetics of intravenously administered 

methylmercury in man. Toxicol Appl Pharmacol 128:251-256. 

Soong, Y-K; Tseng, R; Liu, C; et al. (1991) Lead, cadmium, arsenic and mercury levels in 

maternal and fetal cord-blood. J Formosan Med Assoc 90:59-65. 

Soria, ML; Sanz, P; Martinez, D; et al. (1992) Total mercury and methylmercury in hair, maternal 

and umbilical blood, and placenta from women in the Seville area. Bull Environ Contam Toxicol 

48:494-501. 

Sørensen, N; Murata, K; Budtz-Jørgensen, E; et al. (1999) Prenatal methylmercury exposure as a 

cardiovascular risk factor at seven years of age. Epidemiology 10:370-375. 

http://www.epa.gov/iris/subst/0073.htm
Spyker, JM. (1975) Assessing the impact of low level chemicals on development: behavioral and 

latent effects. Fed Proc 34(9):1835-1844. 

Stern, AH. (1997) Estimation of the interindividual variability in the one-compartment 

pharmacokinetic model for methylmercury: implications for the derivation of a reference dose. 

Regul Toxicol Pharmacol 25:277-288. 

Steurwald, U; Weibe, P; Jorgensen, K; (2000) Maternal seafood diet, methylmercury exposure, 

and neonatal neurologic function. J Pediatr 136(5):599-605. 

Suter, KE. (1975) Studies on the dominant lethal and fertility effects of the heavy metal 

compounds methyl mercuric hydroxide, mercuric chloride, and cadmium chloride in male and 

female mice. Mutat Res 30:365-374. 

Swartout, J; Rice, G. (2000) Uncertainty analysis of the estimated ingestion rates used to derive 

the methylmercury reference dose. Drug Clin Toxicol 23(1):293-306. 

Truska, P; Rosival, I; Balazova, G; et al. (1989) Placental concentrations of cadmium, lead, and 

mercury in mothers and their newborns. J Hyg Epidemiol Microbiol Immunol 33(2):141-147. 

Tsuchiya, H; Mitani, K; Kodama, T; et al. (1984) Placental transfer of heavy metals in normal 

pregnant Japanese women. Arch Environ Health 39(1):11-17. 

U.S. EPA. (1980) Ambient Water Quality Criteria Document for Mercury. Prepared by the Office of 

Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, 

OH for the Office of Water Regulation and Standards, Washington, DC. EPA/440/5-80/058. NTIS 

PB 81-117699. 

U.S. EPA. (1984) Mercury Health Effects Update: Health Issue Assessment. Final Report. 

Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and 

Assessment Office, Cincinnati, OH for the Office of Air Quality Planning and Standards, Research 

Triangle Park, NC. EPA/600/8-84/019F. NTIS PB81-85-123925. 

U.S. EPA. (1987) Peer Review Workshop on Mercury Issues. Environmental Criteria and 

Assessment Office, Cincinnati, OH. Summary report. October 26-27. 

U.S. EPA. (1988) Drinking Water Criteria Document for Inorganic Mercury. Prepared by the Office 

of Health and Environmental Assessment, Environmental Criteria and Assessment Office, 

Cincinnati, OH for the Office of Drinking Water, Washington, DC. EPA/600/X-84/178. NTIS PB89-

192207. 

U.S. EPA. (1995) Mercury Study Report to Congress. Office of Research and Development, 

Washington, DC. External Review Draft. EPA/600/P-94/002Ab. 

U.S. EPA. (1997) Mercury Study Report to Congress. Office of Research and Development, 

Washington, DC. December, 1997. 

U.S. EPA. (2001) Water Quality Criterion for the Protection of Human Health: Methylmercury 

Chapter 4: Risk Assessment for Methylmercury. Office of Science and Technology, Office of 

Water. 

http://www.epa.gov/iris/subst/0073.htm
Vahter, M; Akesson, A; Lind, B; et al. (2000) Longitudinal study of methylmercury and inorganic 

mercury in blood and urine of pregnant and lactating women, as well as in umbilical cord-blood. 

Environ Res 84:186-194. 

WHO (World Health Organization). (1990) Environmental Health Criteria 101: Methylmercury. 

Geneva. 

Yang, J; Jiang, Z; Wan, Y; et al. (1997) Maternal-fetal transfer of metallic mercury via the 

placenta and milk. Ann Clin Lab Sci 27(2):135-141.

_VI.B. Inhalation RfC References

None

_VI.C. Carcinogenicity Assessment References

Betti, C., T. Davini and R. Barale. 1992. Genotoxic activity of methyl mercury chloride and 

dimethyl mercury in human lymphocytes. Mutat. Res. 281(4): 255 260. 

Blakley, B.R. 1984. Enhancement of urethane-induced adenoma formation in Swiss mice exposed 

to methylmercury. Can. J. Comp. Med. 48: 299 302. 

Charbonneau, S.M., I.C. Munro, E.A. Nera et al. 1976. Chronic toxicity of methylmercury in the 

adult cat. Toxicology. 5: 337-349. 

Costa, M., N.T. Christie, O. Cantoni, J.T. Zelikoff, X.W. Wang and T.G. Rossman. 1991. DNA 

damage by mercury compounds: An overview. In: Advances in Mercury Toxicity, T. Suzuki, N. 

Imura and T.W. Clarkson, Ed. Plenum Press, New York, NY. p. 255-273. 

Eriksson, M., L. Hardell, N.O. Berg, T. Moller and O. Axelson. 1981. Soft- tissue sarcomas and 

exposure to chemical substances: A case-referent study. Br. J. Ind. Med. 38: 27 33. 

Eriksson, M., L. Hardell and H.-O. Adami. 1990. Exposure to dioxins as a risk factor for soft-tissue 

sarcoma: A population-based case-control study. J. Natl. Cancer Inst. 82(6): 486 490. 

Fiskesjo, G. 1979. Two organic mercury compounds tested for mutagenicity in mammalian cells 

by use of the cell line V 79-4. Hereditas. 90: 103-109. 

Hardell, L. and M. Eriksson. 1988. The association between soft-tissue sarcomas and exposure to 

phenoxyacetic acids. A new case-referent study. Cancer. 62: 652 656. 

Hardell, L., M. Eriksson, P. Lenner and E. Lundgren. 1981. Malignant lymphoma and exposure to 

chemicals, especially organic solvents, chlorophenols and phenoxy acids: A case-control study. 

Br. J. Cancer. 43: 169 176. 

Heddle, J.R. and W.R. Bruce. 1977. Comparison of the micronucleus and sperm assay for 

mutagenicity with the carcinogenic activities of 61 different agents. In: Origins of Human Cancer, 

H.H. Hiatt, J.D. Watson, J.A. Winsten, Ed. Vol. 4. Cold Spring Harbor Conferences. 

http://www.epa.gov/iris/subst/0073.htm
Hirano, M., K. Mitsumori, K. Maita and Y. Shirasu. 1986. Further carcinogenicity study on 

methylmercury chloride in ICR mice. Jpn. J. Vet. Sci. 48(1): 127 135. 

Janicki, K., J. Dobrowolski and K. Krasnicki. 1987. Correlation between contamination of the rural 

environment with mercury and occurrence of leukemia in men and cattle. Chemosphere. 16: 253 

257. 

Jenssen, D. and C. Ramel. 1980. The micronucleus test as part of a short- term mutagenicity test 

program for the prediction of carcinogenicity evaluated by 143 agents tested. Mutat. Res. 75: 191 

202. 

Kanematsu, N., M. Hara and T. Kada. 1980. Rec assay and mutagenicity studies on metal 

compounds. Mutat. Res. 77: 109-116. 

Mailhes, J.B. 1983. Methylmercury effects on Syrian hamster metaphase II oocyte chromosomes. 

Environ. Mutagen. 5: 679-686. 

Matsumoto, N. and A. Spindle. 1982. Sensitivity of early mouse embryos to methylmercury 

toxicity. Toxicol. Appl. Pharmacol. 64: 108-117. 

Miller, C.T., Z. Zawidska, E. Nagy and S.M. Charbonneau. 1979. Indicators of genetic toxicity in 

leukocytes and granulocytic precursors after chronic methylmercury ingestion by cats. Bull. 

Environ. Contam. Toxicol. 21: 296-303. 

Mitsumori, K., K. Maita, T. Saito, S. Tsuda and Y. Shirasu. 1981. Carcinogenicity of 

methylmercury chloride in ICR mice: Preliminary note on renal carcinogenesis. Cancer Lett. 12: 

305 310. 

Mitsumori, K., K. Takahashi, O. Matano, S. Goto and Y. Shirasu. 1983. Chronic toxicity of 

methylmercury chloride in rats: Clinical study and chemical analysis. Jpn. J. Vet. Sci. 45(6): 747-

757. 

Mitsumori, K., K. Maita and Y. Shirasu. 1984. Chronic toxicity of methylmercury chloride in rats: 

Pathological study. Jpn. J. Vet. Sci. 46(4): 549-557. 

Mitsumori, K., M. Hirano, H. Ueda, K. Maita and Y. Shirasu. 1990. Chronic toxicity and 

carcinogenicity of methylmercury chloride in B6C3F1 mice. Fund. Appl. Toxicol. 14: 179 190. 

Morimoto, K., S. Iijima and A. Koizumi. 1982. Selenite prevents the induction of sister-chromatid 

exchanges by methyl mercury and mercuric chloride in human whole-blood cultures. Mutat. Res. 

102: 183-192. 

Munro, I., E. Nera, S. Charbonneau, B. Junkins and Z. Zawidzka. 1980. Chronic toxicity of 

methylmercury in the rat. J. Environ. Pathol. Toxicol. 3: 437-447. 

Nakai, S. and I. Machida. 1973. Genetic effect of organic mercury on yeast. Mutat. Res. 21(6): 

348. 

Nakazawa, N., F. Makino and S. Okada. 1975. Acute effects of mercuric compounds on cultured 

mammalian cells. Biochem. Pharmacol. 24: 489-493. 

http://www.epa.gov/iris/subst/0073.htm
Newberne, P.M., O. Glaser and L. Friedman. 1972. Chronic exposure of rats to methyl mercury in 

fish protein. Nature. 237: 40-41. 

Ramel, C. 1972. Genetic effects. In: Mercury in the Environment - An Epidemiological and 

Toxicological Appraisal, L. Friberg and J. Vostal, Ed. CRC Press, Cleveland, OH. p. 169-181. (Cited 

in U.S. EPA, 1985). 

Schroeder, H. and M. Mitchener. 1975. Life-time effects of mercury, methyl mercury, and nine 

other trace metals in mice. J. Nutr. 105: 452 458. 

Skerfving, S., K. Hansson and J. Lindsten. 1970. Chromosome breakage in humans exposed to 

methyl mercury through fish consumption. Arch. Environ. Health. 21: 133-139. 

Skerfving, S., K. Hansson, C. Mangs, J. Lindsten and N. Ryman. 1974. Methylmercury-induced 

chromosome damage in man. Environ. Res. 7: 83-98. 

Suter, K.E. 1975. Studies on the dominant-lethal and fertility effects of the heavy metal 

compounds methylmercuric hydroxide, mercuric chloride, and cadmium chloride in male and 

female mice. Mutat. Res. 30: 365-374. 

Tamashiro, H., M. Arakaki, H. Akagi, M. Futatsuka and L.H. Roht. 1984. Causes of death in 

Minamata disease: Analysis of death certificates. Int. Arch. Occup. Environ. Health. 54: 135-146. 

Tamashiro H., Arakaki M., Futatsuka M. and E.S. Lee. 1986. Methylmercury exposure and 

mortality in southern Japan: A close look at causes of death. J. Epidemiol. Comm. Health. 40: 

181-185. 

U.S. EPA. 1980. Ambient Water Quality Criteria Document for Mercury. Prepared by the Office of 

Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, 

OH for the Office of Water Regulation and Standards, Washington, DC. EPA/440/5-80/058. NTIS 

PB81- 117699. 

U.S. EPA. 1984a. Mercury Health Effects Update: Health Issue Assessment. Final Report. 

Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and 

Assessment Office, Cincinnati, OH for the Office of Air Quality Planning and Standards, Research 

Triangle Park, NC. EPA/600/8- 84/019F. NTIS PB81-85-123925. 

U.S. EPA. 1984b. Health Effects Assessment for Mercury. Prepared by the Office of Health and 

Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the 

Office of Emergency and Remedial Response, Washington, DC. EPA/540/1086/042. NTIS PB86-

134533/AS. 

U.S. EPA. 1988. Drinking Water Criteria Document for Inorganic Mercury. Prepared by the Office 

of Health and Environmental Assessment, Environmental Criteria and Assessment Office, 

Cincinnati, OH for the Office of Drinking Water, Washington, DC. EPA/600/X-84/178. NTIS PB89-

192207. 

U.S. EPA. 1993. Summary Review of Health Effects Associated with Mercuric Chloride: Health 

Issue Assessment (Draft). Prepared by the Office of Health and Environmental Assessment, 

Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Air Quality Planning 

and Standards, Research Triangle Park, NC. EPA/600/R-92/199. 

http://www.epa.gov/iris/subst/0073.htm
Date Section Description

U.S. EPA. 1995. Mercury Study Report to Congress. Office of Research and Development, 

Washington, DC. External Review Draft. EPA/600/P-94/002Ab. 

Verschuuren, H.G., R. Kroes, E.M. Den Tonkelaar et al. 1976. Toxicity of methylmercury chloride 

in rats. III. Long-term toxicity study. Toxicology. 6: 107 123. 

WHO (World Health Organization). 1990. Methyl mercury. Vol. 101. Geneva, Switzerland: World 

Health Organization, Distribution and Sales Service, International Programme on Chemical 

Safety. 

Wulf, H.C., N. Kromann, N. Kousgaard, J.C. Hansen, E. Niebuhr and K. Alboge. 1986. Sister 

chromatid exchange (SCE) in Greenlandic eskimos: Dose-response relationship between SCE and 

seal diet, smoking, and blood cadmium and mercury concentrations. Sci. Total Environ. 48: 81-

94. 

_VII. Revision History

Substance Name — Methylmercury (MeHg) 

CASRN — 22967-92-6 

12/01/1988 I.A. Principal study citations added

02/01/1989 I.A. Oral RfD summary is being reevaluated

08/01/1991 VI. Bibliography on-line

01/01/1992 I.A.7. Secondary contact changed

01/01/1992 IV. Regulatory Action section on-line

03/01/1994 I.A.6. Work group review date added

04/01/1994 II. Carcinogenicity assessment now under review

09/01/1994 I.A.6. Work group review date added

10/01/1994 I.A.6. Work group review dates added

11/01/1994 I.A.6. Work group review date added

12/01/1994 I.A.6. Work group review date added

05/01/1995 I.A. Oral RfD summary replaced; new RfD

05/01/1995 VI.A. Oral RfD references replaced

05/01/1995 II. Carcinogenicity assessment on-line

05/01/1995 VI.C. Carcinogenicity assessment references on-line

04/01/1997 III., IV., 

V. 

Drinking Water Health Advisories, EPA Regulatory Actions, and 

Supplementary Data were removed from IRIS on or before April 1997. 

IRIS users were directed to the appropriate EPA Program Offices for 

this information.

07/27/2001 I.A., 

VI.A.

Oral RfD Summary and references replaced

07/31/2001 VI.A. references corrected

http://www.epa.gov/iris/subst/0073.htm
IRIS Home

Chronic Health 

Hazards for NonCarcinogenic Effects

Reference Dose for 

Chronic Oral 

Exposure (RfD)

• Oral RfD 

Summary 

• Principal and 

Supporting 

Studies

• Uncertainty and 

Modifying Factors

• Additional 

Studies/Comments

• Confidence in the 

Oral RfD

• EPA 

Documentation 

and Review

Reference 

Concentration for 

Chronic Inhalation 

Exposure (RfC)

• Inhalation RfC 

Summary

• Principal and 

Supporting 

Studies

• Uncertainty and 

Modifying Factors

• Additional 

Studies/Comments

12/03/2002 I.A.6., 

II.D.2.

Screening-Level Literature Review Findings message has been added.

04/05/2011 I.A.2. Edits made to dose conversion equations.

_VIII. Synonyms

Substance Name — Methylmercury (MeHg) 

CASRN — 22967-92-6 

Last Revised — 07/27/2001

• 22967-92-6

• MeHg

• Methylmercury

• Methylmercury II

• Mercury(1+), methyl-

• Mercury (1+), Methyl-, Ion

• Methyl Mercury

• Methylmercury (II) Cation

• Methylmercury Ion

http://www.epa.gov/iris/subst/0073.htm
• Confidence in the 

Inhalation RfC

• EPA 

Documentation 

and Review

Carcinogenicity 

Assessment for 

Lifetime Exposure

Evidence for Human 

Carcinogenicity

• Weight-ofEvidence 

Characterization

• Human 

Carcinogenicity 

Data

• Animal 

Carcinogenicity 

Data

• Supporting Data 

for 

Carcinogenicity

Quantitative 

Estimate of 

Carcinogenic Risk 

from Oral Exposure

• Summary of Risk 

Estimates

• Dose-Response 

Data

• Additional 

Comments

• Discussion of 

Confidence

Quantitative 

Estimate of 

Carcinogenic Risk 

from Inhalation 

Exposure

• Summary of Risk 

Estimates

• Dose-Response 

Data

• Additional 

Comments

• Discussion of 

Confidence

• EPA 

Documentation, 

Review and, 

Contacts

Bibliography

Revision History

Synonyms

http://www.epa.gov/iris/subst/0073.htm