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Appendix D

Estimates of Human Exposure Doses and Determination of Health Effects

Overview of ATSDR's Methodology for Evaluating Potential Public Health Hazards

To evaluate exposures of eating fish and shellfish from Vieques, ATSDR derived exposure doses and compared them against health-based guidelines. ATSDR also reviewed relevant toxicologic data to obtain information about the toxicity of chemicals of interest. Exposure to a certain chemical does not always result in harmful health effects. The type and severity of health effects expected to occur depend on the exposure concentration, the toxicity of the chemical, the frequency and duration of exposure, and the multiplicity of exposures.

Deriving exposure doses

Exposure doses are expressed in milligrams per kilogram per day (mg/kg/day). When estimating exposure doses, health assessors evaluate chemical concentrations to which people could be exposed, together with the length of time and the frequency of exposure. Collectively, these factors influence an individual's physiological response to chemical exposure and potential outcomes. ATSDR used site-specific information regarding the frequency and duration of exposures. In addition, ATSDR employed several conservative exposure assumptions to estimate exposures.

The following equation was used to estimate ingestion of chemicals by eating fish and shellfish:

Using exposure doses to evaluate potential health hazards

ATSDR analyzes the weight of evidence of available toxicologic, medical, and epidemiologic data to determine whether exposures might be associated with harmful health effects (noncancer and cancer). As part of this process, ATSDR examines relevant health effects data to determine whether estimated doses are likely to result in harmful health effects. As a first step in evaluatingnoncancer effects, ATSDR compares estimated exposure doses to conservative health guideline values, including ATSDR's minimal risk levels (MRLs) and EPA's reference doses (RfDs). The MRLs and RfDs are estimates of daily human exposure to a substance that are unlikely to result in noncancer effects over a specified duration. Estimated exposure doses that are less than these values are not considered to be of health concern. To maximize human health protection, MRLs and RfDs have built in uncertainty or safety factors, making these values considerably lower than levels at which health effects have been observed. The result is that even if an exposure dose is higher than the MRL or RfD, it does not necessarily follow that harmful health effects will occur.

But if health guideline values are exceeded, ATSDR examines the health effects levels discussed in the scientific literature and more fully reviews exposure potential. ATSDR reviews available human studies as well as experimental animal studies. This information is used to describe the disease-causing potential of a particular chemical and to compare site-specific dose estimates with doses shown in applicable studies to result in illness (known as the margin of exposure). For cancer effects, ATSDR compares an estimated lifetime exposure dose to available cancer effects levels (CELs), which are doses that produce significant increases in the incidence of cancer or tumors, and reviews genotoxicity studies to understand further the extent to which a chemical might be associated with cancer outcomes. This process enables ATSDR to weigh the available evidence in light of uncertainties and offer perspective on the plausibility of harmful health outcomes under site-specific conditions.

When comparing estimated exposure doses to actual health effects levels in the scientific literature, ATSDR estimates doses based on more realistic exposure scenarios to use for comparison. In this level of the evaluation, an average concentration⁽⁸⁾ is used to calculate exposure doses to estimate a more probable exposure. This approach is taken because it is highly unlikely that anyone would ingest fish or shellfish with the maximum concentration on a daily basis and for an extended period of time because not every fish or shellfish contains the maximum detected concentration of any given chemical. Therefore, it is more likely that fish or shellfish containing a range of concentrations would be ingested over time. In addition, several chemicals (e.g., arsenic, iron, and lead) were not detected in all samples collected. Therefore, fish or shellfish without any chemical contamination could also be consumed.

Using other methods to evaluate potential health hazards

When dealing with exposure to lead, ATSDR uses a second approach in addition to the traditional methodologies described above. A substantial part of human health effects data for lead are expressed in terms of blood lead level rather than exposure dose. Thus, ATSDR developed a secondary approach to utilize regression analysis with media-specific uptake parameters to estimate what cumulative blood lead level might result from exposure to a given level of contamination. This is accomplished by multiplying the detected concentration by a media-specific slope factor, which is 0.24 micrograms per deciliter (m g/dl) per ppm of lead in fish ingested (ATSDR 1999c). The Centers for Disease Control and Prevention (CDC) have determined that health effects are more likely to be observed if blood lead levels are at or above 10 mg/dl.

Sources for health-based guidelines

By Congressional mandate, ATSDR prepares toxicological profiles for hazardous substances found at contaminated sites. These toxicological profiles were used to evaluate potential health effects from ingestion of fish and shellfish from Vieques. ATSDR's toxicological profiles are available on the Internet at http://www.atsdr.cdc.gov/toxpro2.html or by contacting the National Technical Information Service (NTIS) at 1-800-553-6847. EPA also develops health effects guidelines, and in some cases, ATSDR relied on EPA's guidelines to evaluate potential health effects. These guidelines are found in EPA's Integrated Risk Information System (IRIS)--a database of human health effects that could result from exposure to various substances found in the environment. IRIS is available on the Internet at http://www.epa.gov/iris. For more information about IRIS, please call EPA's IRIS hotline at 1-301-345-2870 or e-mail at Hotline.IRIS@epamail.epa.gov.

Evaluation of Health Hazards Associated with Eating Fish and Shellfish from Vieques

Chemicals not detected

Antimony, thallium, RDX, HMX, 1,3,5-trinitrobenzene, 1,3-dinitrobenzene, 2,4,6-dinitrobenzene, 2,4,6-trinitrotoluene, tetryl, nitrobenzene, 2,4-dinitrotoluene, 2,6-dinitrotoluene, 2-amino-4,6-dinitrotoluene, 4-amino-2,6-dinitrotoluene, 2-nitrotoluene, 3-nitrotoluene, 4-nitrotoluene, and nitroglycerin were analyzed for but not detected in any fish or shellfish sample (see Tables 8 and 9). In addition, nickel was not detected in shellfish (see Table 9). Therefore, none of these chemicals are of health concern for people consuming fish and shellfish around Vieques and will not be discussed further.

Chemicals without health-based guidelines

Essential nutrients (e.g., calcium, magnesium, potassium, and sodium) are important minerals that maintain basic life functions; therefore, certain doses are recommended on a daily basis. Because these chemicals are necessary for life, MRLs and RfDs do not exist for them. They are found in many foods, such as milk, bananas, and table salt. Ingestion of these essential nutrients at the concentrations found in the fish and shellfish from Vieques will not result in harmful health effects and will not be discussed further.

Chemicals below health guidelines for all exposure scenarios

ATSDR derived conservative exposure doses for the metals that were detected in edible samples by using the maximum concentrations found in fish and shellfish in the equation provided above in the Deriving exposure doses section and by comparing the estimated exposure doses to standard health guideline values (MRLs and RfDs). Using the maximum detected concentration for the daily exposure scenario, the resulting exposure doses for aluminum, barium, beryllium, cobalt, manganese, silver, and vanadium were below health guidelines for both fish and shellfish. In addition, cadmium, nickel, and zinc were below the health guidelines in fish ⁽⁹⁾ (see Tables D-1 and D-2 for fish and shellfish, respectively). Therefore, none of these chemicals were detected at a level of health concern in fish and shellfish from Vieques and will not be discussed further.

Chemicals above health guidelines for one or more exposure scenarios

One or more exposure scenarios for arsenic, cadmium (in shellfish), chromium, copper, iron, mercury, selenium, and zinc (in shellfish) resulted in exposure doses higher than the health guideline for that chemical (see Tables D-3 and D-4 for the estimated doses of these metals in fish and shellfish, respectively). However, calculated exposure doses higher than the health guidelines do not automatically mean harmful health effects will occur. Rather, they are an indication that ATSDR should further examine the harmful effect levels reported in the scientific literature and more fully review exposure potential. The remainder of this appendix further evaluates these metals and their realistic exposure potential. Lead is also included in this analysis because a health guideline is not available for lead. The chemical-specific evaluations follow.

Arsenic

Although elemental arsenic sometimes occurs naturally, arsenic is usually found in the environment in two forms--inorganic (arsenic combined with oxygen, chlorine, and sulfur) and organic (arsenic combined with carbon and hydrogen). The organic forms of arsenic are usually less toxic than the inorganic forms (ATSDR 2000a). Arsenic can be found in most foods, with seafood, particularly shellfish, containing the highest concentrations (FDA 1993). Therefore, ingesting fish and shellfish containing arsenic is one way arsenic can enter the body. However, most of the arsenic in fish and shellfish is the less harmful organic form (Cullen 1998; Dabeka et al. 1993; Eisler 1994; Gebel et al. 1998b as cited in ATSDR 2000a; FDA 1993).

Once in the body, the liver changes some of the inorganic arsenic into the less harmful organic form (i.e., by methylation). This process is effective as long as the dose of inorganic arsenic remains below 0.05 mg/kg/day (ATSDR 2000a). Both inorganic and organic forms of arsenic leave the body in urine. Studies have shown that 45-85% of the arsenic is eliminated within one to three days (Buchet et al. 1981a; Crecelius 1977; Mappes 1977; Tam et al. 1979b as cited in ATSDR 2000a); however, some will remain for several months or longer.

Because inorganic arsenic is much more harmful than organic arsenic, ATSDR based its health assessment on the levels of inorganic arsenic that are present. In fish and shellfish, generally about 1-20% of the total arsenic is in the more harmful inorganic form (ATSDR 2000a; Francesconi and Edmonds 1997; NAS 2001b; FDA 1993). The US Food and Drug Administration (FDA) proposes that 10% of the total arsenic be estimated as inorganic arsenic rather than specifically analyze for inorganic arsenic (FDA 1993). To be conservative, ATSDR used a conversion factor of 20% in the numerator of the dose equation described in the Deriving exposure doses section to calculate the estimated dose from exposure to inorganic arsenic in fish and shellfish from Vieques (i.e., ATSDR conservatively assumed that 20% of the total arsenic detected was inorganic arsenic).

Noncancer health effects

Daily exposure to the average concentrations of arsenic (averages = 4.0 ppm in fish and 11.1 ppm in shellfish) in fish and shellfish from a variety of locations would result in exposure doses of 0.0026-0.0072 mg/kg/day for adults and 0.0057-0.0157 mg/kg/day for children. Consuming the average concentration of arsenic from any one location would result in exposure doses ranging from 0.0008-0.0206 mg/kg/day for adults and from 0.0018-0.045 mg/kg/day for children (see Table D-5). As noted above, the metabolism (i.e., how it is broken down in the body) of inorganic arsenic has been extensively studied in humans and animals. ATSDR's estimated doses are well below those that inhibit the body's ability to detoxify or change it to non-harmful forms (doses greater than 0.05 mg/kg/day inhibit detoxification). Therefore, the amount of arsenic that a person consumes in fish and shellfish from Vieques should be controlled by normal metabolic processes in the body.

There is some indication in the scientific literature, however, that some dermal health effects could result from ingesting a lower dose of arsenic--hyperkeratosis and hyperpigmentation were reported in humans exposed to 0.014 mg/kg/day of arsenic in their drinking water for more than 45 years (Tseng et al. 1968 as cited in ATSDR 2000a). However, there is much uncertainty surrounding the reported dose. Because estimates of water intake and dietary arsenic are highly uncertain in this and similar studies, some scientists argue that reported effects may actually be associated with doses higher than 0.014 mg/kg/day. Specifically, the full extent of arsenic intake from dietary sources and the health status of the study population are not well documented.

The estimated exposure doses for every day consumption of shellfish with the average concentration of arsenic exceed the health effects level of 0.014 mg/kg/day for the fish market (Location 5) and overall exposure scenarios (see Table D-5). The disproportionally high arsenic average observed at the fish market is due to the lobsters collected from that location. As shown in the text box, shellfish caught from Vieques displayed noticeably different levels of total arsenic contamination, with lobsters containing by far the highest arsenic body burdens. Therefore, ATSDR evaluated exposure to inorganic arsenic for each individual species. As shown in Table D-6, all estimated doses are within the body's capability to metabolize arsenic (i.e., doses are lower than 0.05 mg/kg/day), although some of the more frequent consumption scenarios for lobster are above the health effects level of 0.014 mg/kg/day. Hence, ATSDR determined how much lobster could safely be consumed given the average concentration of arsenic in lobsters from Vieques. Based on the use of highly conservative assumptions, ATSDR does not expect noncancer health effects to occur in people consuming up to two meals of lobster a week.

Given the fact that the metabolism of arsenic has been well studied in people and the estimated exposure doses for consumption of fish and shellfish are within the body's capability to metabolize arsenic, ATSDR does not expect that people who eat arsenic-contaminated fish and shellfish from Vieques would experience adverse noncancer health effects.

Cancer health effects

The US Department of Health and Human Services (DHHS), the International Agency for Research on Cancer (IARC), the National Toxicology Program (NTP), and EPA have all independently determined that inorganic arsenic is carcinogenic to humans (ATSDR 2000a) . Skin cancer was reported for people exposed to 0.014 mg/kg/day of arsenic in their water for more than 45 years (Tseng et al. 1968 as cited in ATSDR 2000a). As explained above, scientists argue that this CEL may be underestimated (i.e., doses associated with cancer may actually be higher). Additional CELs in the literature generally ranged from 0.01-0.05 mg/kg/day (ATSDR 2000a).

Consuming the average concentration of inorganic arsenic in fish and shellfish from Vieques on a daily basis is estimated to result in lifetime doses of 0.0008-0.0052 mg/kg/day for fish and 0.0018-0.0206 mg/kg/day for shellfish (see adult exposure in Table D-5). Eating arsenic-contaminated fish would not increase your risk of developing cancer. However, some of the exposure scenarios presented in Table D-5 for shellfish resulted in doses higher than some of the CELs. As explained in the noncancer health effects section, lobsters had substantially higher arsenic burdens than conch and land crabs. Therefore, ATSDR evaluated exposure to inorganic arsenic for each individual species of shellfish. As shown in Table D-6, eating conch and land crab would not increase your risk of developing cancer. However, some of the more frequent consumption scenarios for lobster are above the health effects level of 0.01 mg/kg/day. Hence, ATSDR determined how much lobster could safely be consumed given the average concentration of arsenic in lobsters from Vieques. Based on the use of highly conservative assumptions (ATSDR assumed that 20% of the total arsenic is in the inorganic form), ATSDR does not expect cancer health effects to occur in people consuming up to two meals of lobster a week.

Cadmium

Generally, the main sources of cadmium exposure are through smoking cigarettes and, to a lesser extent, eating foods contaminated with cadmium. However, only about 5 to 10% of ingested cadmium is actually absorbed by the body; the majority is passed out of the body in feces (McLellan et al. 1978; Rahola et al. 1973 as cited in ATSDR 1999b). Cadmium that is absorbed goes to the kidneys and liver. Once absorbed, however, cadmium tends to remain in the body for years. The body changes most of the cadmium into a form that is not harmful, but if too much cadmium is absorbed, the liver and kidneys cannot convert all of it into the harmless form (Goyer et al. 1989; Kotsonis and Klaassen 1978; Sendelbach and Klaassen 1988 as cited in ATSDR 1999b).

Noncancer health effects

Cadmium was only detected above health guidelines in shellfish (i.e., fish did not contain levels of cadmium above health concern). The oral health guideline for cadmium is based on a toxicokinetic model which predicts that no adverse health effects would result in people chronically exposed to 0.01 mg/kg/day of cadmium in their food (USEPA 1985 as cited in EPA 1991a).

Daily exposure to the average concentration of cadmium (overall average = 0.36 ppm) in shellfish from a variety of locations would result in exposure doses of 0.0012 mg/kg/day for adults and 0.0026 mg/kg/day for children. Consuming the average concentration in shellfish from any one location would result in exposure doses ranging from 0.0009-0.0016 mg/kg/day for adults and from 0.0019-0.0035 mg/kg/day for children (see Table D-7). Even consuming the highest concentration of cadmium detected in shellfish on a daily basis would result in estimated doses lower than the NOAEL mentioned above (exposure doses = 0.0022 mg/kg/day for adults and 0.0049 mg/kg/day for children; see Table D-4). Therefore, cadmium concentrations in fish and shellfish from Vieques are below levels of health concern for noncancer effects.

Cancer health effects

Studies of cadmium in humans and animals have not found an increase in cancer, however, more research is needed before a definitive conclusion can be reached regarding whether cadmium does or does not cause cancer. As a conservative approach, IARC has determined that cadmium is carcinogenic to humans. DHHS reasonably anticipates that cadmium is a carcinogen. EPA has determined that cadmium, when inhaled, is a probable human carcinogen (ATSDR 1999b). Lifetime exposure to the average concentration of cadmium in fish and shellfish from Vieques is also not expected to result in an increase in cancer because the expected lifetime doses (0.00026 mg/kg/day for fish--see adult exposure in Table D-1; and 0.0009-0.0016 mg/kg/day for shellfish--see adult exposure in Table D-7) are lower than the CEL (increased rates of prostatic adenomas resulted in rats from exposure to 3.5 mg/kg/day of cadmium in food; Waalkes and Rehm 1992 as cited in ATSDR 1999b). Therefore, cadmium concentrations are also below levels of health concern for cancer effects.

Chromium

Chromium can be found in three main forms--chromium 0, chromium III (also known as trivalent chromium), and chromium VI (also known as hexavalent chromium). Chromium VI is more harmful than chromium III, an essential nutrient required by the body. Although some or all of the chromium detected in fish and shellfish from Vieques could be chromium III; as a conservative approach to the health evaluation, ATSDR assumed that all of the chromium was the more harmful chromium VI.

Chromium VI is more easily absorbed than chromium III; therefore, ingesting fish and shellfish containing chromium can lead to harmful forms of chromium entering the body. However, once inside the body, the more harmful chromium VI is converted into the essential nutrient, chromium III. In addition, most of the chromium ingested will exit the body in feces within a few days and never enter the bloodstream. Only a very small amount (0.4 to 2.1%) of chromium can pass through the walls of the intestine and enter the bloodstream (Anderson et al. 1983; Anderson 1986; Donaldson and Barreras 1966 as cited in ATSDR 2000b).

Noncancer health effects

The oral health guideline for chromium VI is based on a study in which no adverse health effects were reported in animals exposed to 2.5 mg/kg/day of chromium VI in their drinking water (MacKenzie et al. 1958 as cited in EPA 1998). Eating fish or shellfish from Vieques on a daily basis would result in chromium doses much lower than this NOAEL, and would not result in harmful health effects.

Daily exposure to the average concentrations of chromium (averages = 0.16 ppm in fish and 0.19 ppm in shellfish) in fish and shellfish from a variety of locations would result in exposure doses of 0.0005-0.0006 mg/kg/day for adults and 0.0011-0.0013 mg/kg/day for children. Consuming the average concentration of chromium from any one location would result in exposure doses ranging from 0.0003-0.0012 mg/kg/day for adults and from 0.0007-0.0027 mg/kg/day for children (see Table D-8). Even consuming the highest concentration of chromium detected in fish and shellfish on a daily basis would result in estimated doses orders of magnitude lower than the NOAEL mentioned above (exposure doses = 0.0042-0.0065 mg/kg/day for adults and 0.0092-0.0141 mg/kg/day for children; see Tables D-3 and D-4). Therefore, chromium concentrations in fish and shellfish from Vieques are well below levels of health concern for noncancer effects.

Cancer health effects

DHHS has determined that certain chromium VI compounds are known human carcinogens when inhaled. IARC has determined that chromium VI is carcinogenic to humans and chromium 0 and chromium III are not classifiable as to their carcinogenicity. EPA has determined that chromium VI in air is a human carcinogen, but insufficient evidence exists to determine whether chromium VI and chromium III in food and water are human carcinogens (ATSDR 2000b). Therefore, despite its carcinogenicity classification, consuming fish and shellfish with chromium is not expected to result in an increase in cancer because the available scientific evidence suggests that oral exposure to chromium would not result in cancer. Animal studies involving chromium ingestion have found no evidence of carcinogenicity. Therefore, chromium concentrations are also below levels of health concern for cancer effects.

Copper

Once ingested, copper is absorbed by the stomach and small intestines as ionic copper or bound to amino acids. Many factors affect the absorption of copper: (1) competition with other metals, such as cadmium and zinc (Davies and Campbell 1977; Hall et al. 1979 as cited in ATSDR 1990); (2) the amount of copper in the stomach (Farrer and Mistilis 1967; Strickland et al. 1972 as cited in ATSDR 1990); (3) certain dietary components; and (4) the form of copper. After being absorbed, copper is transported to the liver by loosely binding to plasma albumin and amino acids (Marceau et al. 1970 as cited in ATSDR 1990). The liver transforms copper into a glycoprotein (ceruloplasmin) and releases it into plasma. About 72% of copper is excreted in feces through bile (Bush et al. 1955 as cited in ATSDR 1990).

Copper is essential for good health because it aids in the absorption and utilization of iron and in the production of hemoglobin, which transports oxygen in the body (ANR 2001). However, even though the body is very good at regulating how much copper enters the bloodstream, very large single or daily intakes can cause harmful health effects (ATSDR 1990). The National Academy of Sciences reports that no adverse effects were observed at doses of 10 mg/day (NAS 2001a).

Very few toxicological and epidemiological studies are available for copper and those that are available suffer from design flaws and involve only a few subjects (NAS 2001a). Therefore, for comparison, ATSDR calculated a daily consumption of copper in fish and shellfish using a modification of the dose equation described in the Deriving exposure doses section (Dose = Conc. x IR ) and compared this daily dose to the level determined by the National Academy of Sciences to be safe (10 mg/day).

Exposure to the average concentrations of copper (averages = 0.56 ppm in fish and 7.8 ppm in shellfish) in fish and shellfish from a variety of locations would increase a child's daily consumption of copper by 0.06-0.89 mg/day and an adult's daily consumption by 0.13-1.77 mg/day. Consuming the average concentration of copper from any one location would result in daily dose increases from 0.1-2.36 mg/day for adults and from 0.05-1.18 mg/day for children (see Table D-9). Even consuming the maximum concentration of copper would only increase a child's daily consumption by 0.9-2.0 mg/day and an adult's daily consumption by 1.9-4.0 mg/day.

The median copper intake in the United States from food is approximately 1.0-1.6 mg/day (NAS 2001a). Therefore, the relatively small daily increases in consumption (from eating fish and shellfish from Vieques) are not likely to increase a person's daily dose above the National Academy of Sciences' NOAEL of 10 mg/day. Additionally, eating fish and shellfish would help a person consume the recommended dietary intake for copper. Therefore, copper concentrations in fish and shellfish from Vieques are not expected to cause adverse health effects.

Iron

Iron is an important mineral, assisting in the maintenance of basic life functions. It combines with protein and copper to make hemoglobin, which transports oxygen in the blood from the lungs to other parts of the body, including the heart. It also aids in the formation of myoglobin, which supplies oxygen to muscle tissues (ANR 2001). Without sufficient iron, the body cannot produce enough hemoglobin or myoglobin to sustain life. Iron deficiency anemia is a condition occurring when the body does not receive enough iron.

The oral health guideline for iron is based on dietary intake data collected as part of EPA's Second National Health and Nutrition Examination Survey in which no adverse health effects were associated with average iron intakes of 0.15-0.27 mg/kg/day. These levels were determined to be sufficient for protection against iron deficiency, but also low enough to not cause harmful health effects.

Daily exposure to the average concentrations (averages = 6.8 ppm in fish and 36.3 ppm in shellfish) of iron in fish and shellfish from a variety of locations would result in exposure doses of 0.022-0.118 mg/kg/day for adults and 0.048-0.258 mg/kg/day for children. Consuming the average concentration of iron from any one location would result in exposure doses ranging from 0.005-0.169 mg/kg/day for adults and from 0.011-0.37 mg/kg/day for children (see Table D-10). Some of the estimated doses for shellfish slightly exceed the NOAELs of 0.15-0.27 mg/kg/day. However, estimated doses that slightly exceed the NOAELs do not indicate that an adverse health effect will occur because NOAELs indicate a level in which no adverse health effects were observed. Additionally, it is highly unlikely that anyone would eat shellfish on a daily basis, rather a variety of different foods would be consumed. Further, the body uses a homeostatic mechanism to keep iron burdens at a constant level despite variations in the diet (Eisenstein and Blemings 1998).

Generally, iron is not considered to cause harmful health effects except when swallowed in extremely large doses, such as in the case of accidental drug ingestion. Acute iron poisoning has been reported in children under 6 years of age who have accidentally overdosed on iron-containing supplements for adults. According to the FDA, doses greater than 200 mg per event could poison or kill a child (FDA 1997). However, doses of this magnitude are generally the result of children ingesting iron pills. For comparison, ATSDR calculated a daily consumption from exposure to the average concentration of iron in fish and shellfish using a modification of the dose equation described in the Deriving exposure doses section (Dose = Conc. x IR ).

Exposure to the average concentration of iron (averages = 6.8 ppm in fish and 36.3 ppm in shellfish) in fish and shellfish from a variety of locations would increase a child's daily consumption of iron by 0.8-4.1 mg/day and an adult's daily consumption by 1.5-8.2 mg/day. Consuming the average concentration of iron from any one location would result in daily dose increases from 0.4-11.8 mg/day for adults and from 0.2-5.9 mg/day for children (see Table D-11).

The median daily intake of dietary iron is roughly 11-13 mg/day for children 1 to 8 years old, 13-20 mg/day for adolescents 9 to 18 years old, 16-18 mg/day for adult men, and 12 mg/day for adult women (NAS 2001a). Therefore, the daily increases in consumption (from eating fish and shellfish from Vieques) are not likely to cause a person's daily dose to exceed levels known to induce poisoning (e.g., greater than 200 mg/event). In addition, eating fish and shellfish would help a person meet the recommended dietary intakes for iron. Therefore, ATSDR does not expect that people who eat fish and shellfish from Vieques would experience adverse health effects.

Lead

Ingesting lead in fish and shellfish will cause some lead to enter the body and bloodstream. The amount of lead that enters the body depends on how old you are because more lead enters the blood in children than in adults (Alexander et al. 1974; Blake et al. 1983; James et al. 1985; Rabinowitz et al. 1980; Ziefler et al. 1978 as cited in ATSDR 1999c). Within a few weeks, 99% of the amount of lead absorbed by adults will exit in urine and feces (Rabinowitz et al. 1977 as cited in ATSDR 1999c), whereas only about 68% of the lead taken into children will leave their bodies (Ziegler et al. 1978 as cited in ATSDR 1999c). Once in the body, lead will travel to soft tissues, such as the liver, kidneys, lungs, brain, spleen, muscles, and heart. After several weeks of continual exposure, most of the lead moves from the soft tissue into bones and teeth. In adults, about 94% of the total amount of lead in their bodies can be found in bones. In children, about 73% of lead in their bodies is stored in their bones (Barry 1975 as cited in ATSDR 1999c).

Noncancer health effects

Health effects from chronic exposure to lead have not been documented in humans. However, no adverse effects were observed in animals chronically exposed to 0.57-27 mg/kg/day of lead (ATSDR 1999c). Eating fish and shellfish from Vieques on a daily basis would result in lead doses much lower than these NOAELs.

Daily exposure to the average concentrations of lead (averages = 0.27 ppm in fish and 0.25 ppm in shellfish) in fish and shellfish from a variety of locations would result in exposure doses of 0.0008-0.0009 mg/kg/day for adults and 0.0018-0.0019 mg/kg/day for children. Consuming the average concentration of lead from any one location would result in exposure doses ranging from 0.0006-0.0034 mg/kg/day for adults and from 0.0012-0.0075 mg/kg/day for children (see Table D-12). Even consuming the highest concentration of lead detected in fish and shellfish on a daily basis would result in estimated doses much lower than the NOAELs of 0.57-27 mg/kg/day (exposure doses = 0.0018-0.0063 mg/kg/day for adults and 0.0040-0.0138 mg/kg/day for children; see Tables D-3 and D-4).

To more fully evaluate chronic exposure in adults and children, ATSDR determined the blood lead level expected to result from exposure to lead in fish and shellfish from Vieques using the formula described in the Using other methods to evaluate potential health hazards section. Exposure to the average concentrations of lead in fish and shellfish from a variety of locations is estimated to result in blood lead levels of 0.06 m g/dl--well below CDC's level of concern (10 mg/dl). Consuming the average concentration of lead from any one location would result in blood lead levels ranging from 0.04-0.25 mg/dl (see Table D-13). Even consuming the highest concentration of lead on a daily basis would result in very low blood lead levels (0.14-0.47 m g/dl). Therefore, lead concentrations in fish and shellfish from Vieques are well below levels of health concern for noncancer effects.

Cancer health effects

Although some animal testing has shown that kidney tumors develop if animals are given large doses of lead, no evidence exists that lead causes cancer in humans. Based on the available research, however, DHHS has determined that lead acetate and lead phosphate can reasonably be expected to cause cancer. To evaluate potential increases in cancer from exposure to lead, ATSDR compared the lifetime exposure doses for adults (0.0006-0.0034 mg/kg/day for fish and 0.0006-0.0009 mg/kg/day for shellfish; see adult exposure in Table D-12) to the CELs reported in the literature (renal tubular adenomas and carcinomas resulted in animals exposed to 27 to 371 mg/kg/day of lead in food and water; ATSDR 1999c). But because of the high doses of lead used, ATSDR cautions against using these animal studies to predict whether cancer will actually occur in humans. Even so, the CELs are much higher than the doses expected to result from lifetime exposure to lead in fish and shellfish from Vieques. Therefore, lead concentrations are also below levels of health concern for cancer effects.

Mercury

Mercury exists naturally in the environment in several different forms: metallic mercury (also known as elemental mercury), inorganic mercury, and organic mercury. Metallic mercury is the pure form of mercury. Inorganic mercury is formed when metallic mercury combines with elements such as chlorine, sulfur, or oxygen. Organic mercury is formed when mercury combines with carbon. Microorganisms (bacteria and fungi) and natural processes can change mercury from one form to another. The most common organic mercury compound generated through these processes is methylmercury.

The different forms of mercury are absorbed and distributed differently in the body.

• When small amounts of metallic mercury are ingested, only about 0.01% of the mercury will enter the body through the stomach or intestines (Sue 1994; Wright et al. 1980 as cited in ATSDR 1999a). More metallic mercury can be absorbed if one suffers from a gastrointestinal tract disease. The small amount of metallic mercury that enters the body will accumulate in the kidneys and the brain, where it is readily turned into inorganic mercury. It can stay in the body for weeks or months, but most mercury is eventually excreted through urine, feces, and exhaled breath.
• Typically, less than 10% of inorganic mercury is absorbed through the stomach and intestines. But it has been reported that up to 40% can be absorbed in the intestinal tract (Clarkson 1971; Morcillo and Santamaria 1995; Nielson and Anderson 1990, 1992; Piotrowski et al. 1992 as cited in ATSDR 1999a). Once in the body, a small amount of the inorganic mercury can be converted into metallic mercury, which will be excreted or stored as described above. Inorganic mercury enters the bloodstream and moves to many different tissues, but will mostly accumulate in the kidneys. Inorganic mercury does not easily enter the brain. It can remain in the body for several weeks or months and is excreted through urine, feces, and exhaled breath.
• Methylmercury is the most studied organic mercury compound. It is readily absorbed in the gastrointestinal tract (about 95% absorbed) and can easily enter the bloodstream (Aberg et al 1969; Al-Shahristani et al. 1976; Miettinen 1973 as cited in ATSDR 1999a). It moves rapidly to various tissues and the brain, where methylmercury can be turned into inorganic mercury, which can remain in the brain for long periods. Slowly, over months, methylmercury will leave the body, mostly as inorganic mercury in the feces.

The organic form of mercury is much more harmful than the metallic and inorganic forms. In fish tissue, mercury is present predominantly as methylmercury (about 85%), the more toxic form (Jones 1996). Therefore, to be conservative, ATSDR assumed that all the mercury detected in fish and shellfish was methylmercury. The oral health guideline for methylmercury is based on a study in which people who were exposed to 0.0013 mg/kg/day of methylmercury in their food did not experience any adverse health effects⁽¹⁰⁾(Davidson et al. 1998 as cited in ATSDR 1999a). Eating fish and shellfish from Vieques would result in mercury doses much lower than this NOAEL and would not result in harmful health effects.

Daily exposure to the average concentrations of mercury (averages = 0.12 ppm in fish and 0.03 ppm in shellfish) in fish and shellfish from a variety of locations on a daily basis would result in estimated doses of 0.0001-0.0004 mg/kg/day for adults and 0.0002-0.0009 mg/kg/day for children. Consuming the average concentration of mercury from any one location would result in exposure doses ranging from 0.0001-0.0005 mg/kg/day for adults and from 0.0001-0.0011 mg/kg/day for children (see Table D-14). All of the exposure doses are below the NOAEL of 0.0013 mg/kg/day.

Furthermore, this is a very conservative estimation of mercury exposure because typically about 85% of total mercury in fish is methylmercury, the most prevalent organic form of mercury (Jones 1996). However, in this sampling, only 36-78% of total mercury was methylmercury (three fish and one lobster were analyzed for both total mercury and methylmercury). People who eat fish and shellfish from Vieques are actually being exposed to a lower amount of the harmful form of mercury than what ATSDR calculated. Therefore, the mercury concentrations present in the fish and shellfish from Vieques are well below levels of health concern.

Selenium

Selenium is an essential nutrient that protects cell membranes, is an antioxidant in Vitamin E, and decreases the risk of cancer and heart disease (ANR 2001). The Dietary Reference Intake for maintenance of good health is 55 m g/day (NAS 2000 as cited in ATSDR 2001b). However, consuming too much selenium could lead to harmful health effects.

Absorption studies in humans reported that 80-97% of ingested selenium is absorbed in the gastrointestinal tract (Griffiths et al 1976; Martin et al. 1989a; Thomson 1974; Thomson and Stewart 1974; Thomson et al. 1977 as cited in ATSDR 2001b). Therefore, consuming fish or shellfish with elevated levels will cause some selenium to enter the body and bloodstream. Once in the body, selenium tends to be found at the highest concentrations in the liver and kidneys (Cavalieri et al. 1966; Heinrich and Kelsey 1955; Jereb et al. 1975; Thomson and Stewart 1973 as cited in ATSDR 2001b). Within 24 hours, most of the selenium will leave the body in urine, feces, and to a lesser extent though sweat (Kuikka and Nordman 1978; Levander et al. 1987; Thomson and Stewart 1974 as cited in ATSDR 2001b). Throughout the first week of exposure, about half the selenium will leave the body every day. After the first week, selenium is eliminated more slowly (Thomson and Stewart 1974 as cited in ATSDR 2001b).

The oral health guideline for selenium is based on two studies in which no adverse health effects were reported in people who were exposed to 0.015 mg/kg/day of selenium in their food over their lifetime and dermal health effects (selenosis: sloughing of nails and brittle hair) were observed when the people were exposed to 0.023 mg/kg/day of selenium (Yang and Zhou 1994 as cited in ATSDR 2001b; Yang et al. 1989b as cited in EPA 1991b). Eating fish or shellfish from Vieques on a daily basis would result in selenium doses lower than the NOAEL and health effects level, and would not result in harmful health effects.

Daily exposure to the average concentrations of selenium (averages = 0.98 ppm in fish and 0.8 ppm in shellfish) in fish and shellfish from a variety of locations would result in exposure doses of 0.0026-0.0032 mg/kg/day for adults and 0.0057-0.007 mg/kg/day for children. Consuming the average concentration of selenium from any one location would result in exposure doses ranging from 0.0024-0.0037 mg/kg/day for adults and from 0.0052-0.0082 mg/kg/day for children (see Table D-15). All of these exposure doses are well below the NOAEL mentioned above (0.015 mg/kg/day). Therefore, selenium concentrations in fish and shellfish from Vieques are below levels of health concern.

Zinc

Zinc is an essential nutrient that is needed by the body for normal growth, bone formation, brain development, behavioral response, reproduction, fetal development, sensory function, immune function, membrane stability, and wound healing. Too little zinc can lead to poor health, reproductive problems, and a lowered resistance to disease (ATSDR 1994).

Zinc absorption in humans (8-81%) varies with the amount of zinc ingested and the amount and kind of food eaten (Aamodt et al. 1983; Hunt et al. 1991; Istfan et al. 1983; Reinhold et al. 1991; Sandstrom and Abrahamson 1989; Sandstrom and Cederblad 1980; Sandstrom and Sandberg 1992 as cited in ATSDR 1994). The body uses a homeostatic mechanism to control zinc absorption in the gastrointestinal tract (Davies 1980 as cited in ATSDR 1994). People with adequate nutritional levels of zinc tend to absorb 20-30% of ingested zinc, whereas people with zinc deficiencies absorb more (Johnson et al. 1988; Spencer et al. 1985 as cited in ATSDR 1994). Zinc is one of the most abundant trace metals in the body. Muscle and bone contain about 90% (60% and 30%, respectively) of the total amount of zinc in the body (Wastney et al. 1986 as cited in ATSDR 1994). Zinc can also be found in the liver, gastrointestinal tract, kidney, skin, lung, brain, heart, pancreas, prostate, retina, and sperm (Bentley and Gribb 1991; Drinker and Drinker 1928; Forssen 1972; He et al. 1991; Llobet et al. 1988a as cited in ATSDR 1994).

Zinc was only detected above health guidelines in shellfish (i.e., fish did not contain levels of zinc above health concern). The oral health guideline for zinc is based on a study in which hematological health effects (e.g., decreased superoxide dismutase activity, hematocrit, and ferritin) were observed when people were given doses of 0.83 mg/kg/day of zinc in capsule form for 10 weeks (Yadrick et al. 1989 as cited in ATSDR 1994 and EPA 1992) and is supported by several other studies that investigated effects from zinc supplementation (Black et al. 1988; Chandra 1984; Festa et al. 1985; Fischer et al. 1984; Hooper et al. 1980; L'Abbe and Fischer 1984a,b; Pennington et al. 1989; Prasad et al. 1978; Simko et al. 1984 as cited in EPA 1992). Eating shellfish from Vieques on a daily basis would result in zinc doses lower than this health effects level, and would not result in harmful health effects.

Daily exposure to the average concentration of zinc in shellfish (overall average = 30.1 ppm) from a variety of locations would result in exposure doses of 0.098 mg/kg/day for adults and 0.214 mg/kg/day for children. Consuming the average concentration of zinc from any one location would result in exposure doses ranging from 0.026-0.147 mg/kg/day for adults and from 0.057-0.321 mg/kg/day for children (see Table D-16). All of these exposure doses are below the health effects level mentioned above (0.83 mg/kg/day). Further, as cited above, the body controls zinc absorption to keep body burdens at a constant level. Therefore, zinc concentrations in fish and shellfish from Vieques are below levels of health concern.

Multiple Chemicals

Several studies, including those conducted by the National Toxicology Program in the United States and the TNO Nutrition and Food Research Institute in the Netherlands, among others, generally support the conclusion that if each individual chemical is at a concentration not likely to produce harmful health effects (as is the case on Vieques ), exposures to multiple chemicals are also not expected to be of health concern (for reviews, see Seed et al. 1995; Feron et al. 1993).

Special Case: Snapper

Universidad Metropolitana reported that yellowtail snapper was the most commonly consumed species of fish (Caro et al. 2000). Through talking with several Vieques fishermen and residents, including the petitioner, ATSDR also found that snapper were more commonly sought after, caught, and consumed than any other species of fish. Therefore, ATSDR also considered a situation where people ate snapper on a daily basis and evaluated this special scenario using the same methodology that was used previously for people who consume a variety of fish species.

Chemicals not detected

Antimony, cadmium, thallium, vanadium, HMX, RDX, 1,3,5-trinitrobenzene, 1,3-dinitrobenzene, 2,4,6-dinitrobenzene, 2,4,6-trinitrotoluene, tetryl, nitrobenzene, 2,4-dinitrotoluene, 2,6-dinitrotoluene, 2-amino-4,6-dinitrotoluene, 4-amino-2,6-dinitrotoluene, 2-nitrotoluene, 3-nitrotoluene, 4-nitrotoluene, and nitroglycerin were analyzed for but not detected in snapper. Therefore, none of these chemicals are of health concern for people consuming snapper from Vieques.

Chemicals without health-based guidelines

Essential nutrients (e.g., calcium, magnesium, potassium, and sodium) are important minerals that maintain basic life functions; therefore, certain doses are recommended on a daily basis. Because these chemicals are necessary for life, MRLs and RfDs do not exist for them. They are found in many foods, such as milk, bananas, and table salt. Ingestion of these essential nutrients at the concentrations found in snapper will not result in harmful health effects.

Chemicals below health guidelines

Using the maximum concentration detected in snapper and assuming that snapper is consumed every day, the resulting exposure doses for aluminum, barium, beryllium, chromium, cobalt, iron, manganese, nickel, silver, and zinc were below the conservative health guidelines (see Table D-17). Therefore, none of these chemicals were detected at a level of health concern in snapper.

Chemicals above health guidelines

Eating snapper with the maximum concentration of arsenic, copper, mercury, and selenium every day resulted in exposure doses higher than the health guidelines (see Table D-17). In addition, because a health guideline is not available for lead, ATSDR further examined the harmful effect levels reported in the scientific literature and more fully reviewed exposure potential for these four chemicals and lead. The toxicology and health effects of each of these chemicals have been explained in greater detail previously in this appendix.

Arsenic

Eating snapper from Vieques every day would result in arsenic exposure doses of 0.0037 mg/kg/day for adults and 0.008 mg/kg/day for children (see Table D-18). These doses are within the body's capacity (i.e., less than 0.05 mg/kg/day) to metabolize arsenic into non-harmful forms and are lower than the health effect level of 0.014 mg/kg/day. In addition, the lifetime exposure dose for adults (0.0037 mg/kg/day) is well below the CELs reported in the literature (0.01 to 0.05 mg/kg/day). Therefore, arsenic concentrations in snapper are well below levels of health concern for noncancer and cancer health effects.

Copper

Eating snapper from Vieques would increase a child's daily consumption of copper by 0.12 mg/day and an adult's daily consumption by 0.23 mg/day (see Table D-18). These relatively small daily increases in consumption are not likely to increase a person's daily dose above the National Academy of Sciences' NOAEL of 10 mg/day. Therefore, copper concentrations in snapper are not expected to cause adverse health effects.

Lead

Eating snapper from Vieques every day would result in exposure doses lower than the NOAELs of 0.57-27 mg/kg/day (0.0007 mg/kg/day for adults and 0.0015 mg/kg/day for children; see Table D-18). In addition, the resulting blood lead level is estimated to be 0.05 m g/dl, well below CDC's level of concern (10 mg/dl). Finally, the lifetime exposure dose for adults (0.0007 mg/kg/day) is orders of magnitude below the CELs reported in the literature (27 to 371 mg/kg/day). Therefore, lead concentrations in snapper are well below levels of health concern for noncancer and cancer health effects.

Mercury

Eating snapper from Vieques every day would result in exposure doses to mercury (0.0002 mg/kg/day for adults and 0.0004 mg/kg/day for children; see Table D-18) lower than the NOAEL of 0.0013 mg/kg/day. Therefore, mercury concentrations in snapper are well below levels of health concern.

Selenium

Eating snapper from Vieques every day would result in exposure doses to selenium (0.0036 mg/kg/day for adults and 0.0079 mg/kg/day for children; see Table D-18) below the NOAEL of 0.015 mg/kg/day. Therefore, selenium concentrations in snapper are well below levels of health concern.

Special Case: Boxfish

While on Vieques, ATSDR met with the petitioner, who at that time, specifically requested ATSDR to collect and analyze boxfish from the fish market. At the request of ATSDR, the petitioner had compiled a list of fish caught and eaten on Vieques and reported that Chapín (boxfish; e.g., trunkfish and cowfish) are the preferred fish to use as filling in pastelillos. Realizing that the results and conclusions would be limited⁽¹¹⁾ , ATSDR purchased a honeycomb cowfish (Lactophrys polygonia) from the fish market for analysis.

Chemicals not detected

Antimony, beryllium, cadmium, cobalt, iron, lead, manganese, mercury, nickel, silver, thallium, vanadium, HMX, RDX, 1,3,5-trinitrobenzene, 1,3-dinitrobenzene, 2,4,6-dinitrobenzene, 2,4,6-trinitrotoluene, tetryl, nitrobenzene, 2,4-dinitrotoluene, 2,6-dinitrotoluene, 2-amino-4,6-dinitrotoluene, 4-amino-2,6-dinitrotoluene, 2-nitrotoluene, 3-nitrotoluene, 4-nitrotoluene, and nitroglycerin were analyzed for but not detected (see Table 10). Therefore, none of these chemicals were detected at a level of health concern in this representative sample.

Chemicals without health-based guidelines

Essential nutrients (e.g., calcium, magnesium, potassium, and sodium) are important minerals that maintain basic life functions; therefore, certain doses are recommended on a daily basis. Because these chemicals are necessary for life, MRLs and RfDs do not exist for them. They are found in many foods, such as milk, bananas, and table salt. Ingestion of these essential nutrients will not result in harmful health effects.

Chemicals below health guidelines

Using the detected concentration in the representative cowfish sample and assuming that boxfish are consumed every day, the resulting exposure doses for chromium and copper were below the conservative health guidelines (see Table D-19). Therefore, none of these chemicals were detected at a level of health concern.

Chemicals above health guidelines

Eating boxfish every day with the concentrations of arsenic and selenium detected in the representative cowfish sample resulted in exposure doses higher than the health guidelines (see Table D-19). Therefore, ATSDR further examined the harmful effect levels reported in the scientific literature and more fully reviewed exposure potential for these two chemicals. The toxicology and health effects of each of these chemicals have been explained in greater detail previously in this appendix.

Arsenic

Eating boxfish every day with arsenic levels similar to those found in the representative cowfish sample would result in arsenic exposure doses of 0.019 mg/kg/day for adults and 0.042 mg/kg/day for children (see Table D-19). These doses are within the body's capacity (i.e., less than 0.05 mg/kg/day) to metabolize arsenic into non-harmful forms, but are slightly higher than the health effect level of 0.014 mg/kg/day. However, as stated previously, there is much uncertainty surrounding this reported dose and some scientists argue that reported effects may actually be associated with doses higher than 0.014 mg/kg/day. The lifetime exposure dose for adults is within the range of CELs reported in the literature (0.01 to 0.05 mg/kg/day). However, this estimated dose is based upon a hypothetical exposure situation (eating boxfish from Vieques every day), using highly conservative assumptions (ATSDR assumed that 20% of the total arsenic is in the inorganic form.

Given the fact that the metabolism of arsenic has been well studied in people and the estimated exposure doses are within the body's capability to metabolize arsenic, ATSDR does not expect that people who eat boxfish with similar arsenic levels would experience adverse health effects. Furthermore, the representative cowfish sample did not contain higher levels of arsenic than FDA's level of concern for average consumption (76 ppm; FDA 1993). Based upon this one cowfish sample, boxfish are safe to eat and only under highly unlikely, hypothetical scenarios with several levels of conservatism built into the evaluation would the arsenic levels be a problem for people eating more than two meals of boxfish a week for a lifetime.

Selenium

Eating boxfish every day with concentrations of selenium similar to the representative cowfish sample would result in exposure doses of 0.008 mg/kg/day for adults and 0.018 mg/kg/day for children (see Table D-19). Both doses are below the health effects level of 0.023 mg/kg/day. Therefore, selenium concentrations are below levels of health concern.

Evaluating Health Concerns Using Fish Fillet Data from Universidad Metropolitana

Universidad Metropolitana (Caro et al. 2000) sampled fish fillets for arsenic, cadmium, lead, mercury, selenium, and zinc (see Table 3).

Chemicals below health guidelines

Using the maximum concentration detected by Universidad Metropolitana and assuming that fish is consumed every day, the resulting exposure doses for cadmium and zinc were below the conservative health guidelines (see Table D-20). Therefore, these two chemicals were not detected at a level of health concern.

Chemicals above health guidelines

Eating snapper with the maximum concentration of arsenic, mercury, and selenium every day resulted in exposure doses higher than the health guidelines (see Table D-20). In addition, because a health guideline is not available for lead, ATSDR further examined the harmful effect levels reported in the scientific literature and more fully reviewed exposure potential for these three chemicals and lead. The toxicology and health effects of each of these chemicals has been explained in greater detail previously in this appendix.

Arsenic

Eating fish from fish markets on Vieques and the Parquera area on the mainland of Puerto Rico every day would result in exposure doses to arsenic of 0.0008 mg/kg/day for adults and 0.0017 mg/kg/day for children (see Table D-21). These doses are within the body's capacity (i.e., less than 0.05 mg/kg/day) to metabolize arsenic into non-harmful forms and are lower than the health effect level of 0.014 mg/kg/day. In addition, the lifetime exposure dose for adults (0.0008 mg/kg/day) is well below the CELs reported in the literature (0.01 to 0.05 mg/kg/day). Therefore, arsenic concentrations are well below levels of health concern for noncancer and cancer health effects.

Lead

Eating fish every day would result in exposure doses lower than the NOAELs of 0.57-27 mg/kg/day (0.0006 mg/kg/day for adults and 0.0014 mg/kg/day for children; see Table D-21). In addition, the resulting blood lead level is estimated to be 0.05 m g/dl, well below CDC's level of concern (10 mg/dl). Finally, the lifetime exposure dose for adults (0.0006 mg/kg/day) is orders of magnitude below the CELs reported in the literature (27 to 371 mg/kg/day). Therefore, lead concentrations in fish collected from fish markets on Vieques and the Parquera area on the mainland of Puerto Rico are well below levels of health concern for noncancer and cancer health effects.

Mercury

Eating fish from fish markets on Vieques and the Parquera area on the mainland of Puerto Rico every day would result in exposure doses to mercury (0.0001 mg/kg/day for adults and 0.0002 mg/kg/day for children; see Table D-21) lower than the NOAEL of 0.0013 mg/kg/day. Therefore, mercury concentrations are well below levels of health concern.

Selenium

Eating fish every day would result in exposure doses to selenium (0.0019 mg/kg/day for adults and 0.0043 mg/kg/day for children; see Table D-21) below the NOAEL of 0.015 mg/kg/day. Therefore, selenium concentrations in fish from fish markets on Vieques and the Parquera area on the mainland of Puerto Rico are well below levels of health concern.

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⁸ Averages were calculated using detected concentrations only and do not take into account nondetected values. Even though this tends to overestimate the true average values, ATSDR chose to base its health evaluations on the more conservative averages to be more protective of public health.

⁹ Nickel was not detected in shellfish. Estimated doses for zinc were above health guidelines in shellfish.

¹⁰ The chronic oral MRL for methylmercury is based upon the Seychelles Child Development Study (SCDS), in which over 700 mother-infant pairs have, to date, been followed and tested from parturition through 66 months of age. The Seychellois regularly consume a large quantity and variety of ocean fish, with 12 fish meals per week representing a typical methylmercury exposure. The results of the 66-month testing in the SCDS revealed no evidence of adverse effects attributable to chronic ingestion of low levels (median total mercury concentration in 350 fish sampled from 25 species consumed by the Seychellois was <1 ppm (range, 0.004-0.75 ppm)) of methylmercury in fish. In this study, developing fetuses were exposed in utero through maternal fish ingestion before and during pregnancy. Neonates continued to be exposed to maternal mercury during breastfeeding (i.e., some mercury is secreted in breast milk), and methylmercury exposure from the regular diet continued after the gradual post-weaning shift to a fish diet (Davidson et al. 1998 as cited in ATSDR 1999a).

¹¹ It is not unusual for different samples of the same species or family to contain varying chemical concentrations; therefore, other boxfish samples may contain higher or lower levels of these chemicals. There are not enough data from this one sample upon which to base any meaningful health decisions for consumption of boxfish.