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The GESAMP evaluation of potentially harmful substances in fish and other seafood with special reference to carcinogenic substances
Aquatic Toxicology, 11 (1988) 379-393
379
Elsevier
A Q T 00303
The GESAMP evaluation of potentially harmful substances in fish and other seafood with special reference to carcinogenic substances Lars Friberg* Department of Environmental Hygiene, Karolinska Institute, Stockholm, Sweden; National Institute of Environmental Medicine, Stockholm, Sweden (Received 16 September 1986; accepted 15 April 1987)
The
joint
Group
of
Experts
on
the Scientific
Aspects
of
Marine
Pollution,
GESAMP
(IMO/FAO/UNESCO/WMO/WHO/IAEA/UN/UNEP), has evaluated two groups of metals, (1) cadm i u m , lead and tin, and (2) arsenic, mercury and selenium, and has preliminarily discussed risks for carcinogenic effects arising from pollutants. These evaluations are based on work carried out within the G E S A M P Working Group 13 and cover hazards to living resources as well as to h u m a n health. In this presentation only the h u m a n health aspects are discussed. Only under exceptional circumstances will c a d m i u m intake from fish constitute an important part of the total daily intake via food. High consumption of certain shellfish may considerably increase the intake. Lead in seafood does not greatly contribute to the daily intake of lead. The contribution o f seafood to the daily intake of tin is low. However, more data are needed for trimethyltin. Exposure to arsenic via seafood m a y be substantial. Most of this arsenic is in the form of arsenobetaine, which is considered relatively atoxic. Extreme seafood consumption m a y give rise to an intake of several hundred micrograms of inorganic arsenic per day; an exposure level which over a lifetime m a y be related to a significant increase in skin cancer. Groups with high fish intake or intake of fish with a high methylmercury content can easily exceed the W H O / F A O provisional tolerable intake level. Pregnant women constitute a special risk group. A coordinated research approach on an international basis is needed to obtain the necessary data to establish valid guidelines. Selenium does not pose a toxicological problem. Its importance as related to different mercury c o m p o u n d s is discussed. Preliminary evaluations of the risks for carcinogenic effects have been carried out, partly in collaboration with the W H O International Agency for Research on Cancer. Taking all the evidence into account it was considered as a matter o f urgency to mobilize the necessary support for the further development and acceleration of work on the impact of carcinogenic substances on marine organisms and the implications for public health. Key words: Marine pollution; Cancer; G E S A M P ; Mercury; Arsenic; PCB; Hydrocarbons Presented at the Symposium "Toxic Chemicals and Aquatic Life: Research and M a n a g e m e n t " , September 16-18, 1986, Seattle, Washington, U.S.A.
Correspondence to: L. Friberg, National Institute of Environmental Medicine, 104 01 Stockholm, Sweden. * C h a i r m a n of the G E S A M P Working Group 13. 0166-445X/88/$ 03.50 © 1988 Elsevier Science Publishers B.V. (Biomedical Division)
380 INTRODUCTION
GESAMP, the joint Group of Experts on the Scientific Aspects of Marine Pollution, is an international body sponsored by several international organizations, IMO, FAO, UNESCO, WMO, WHO, IAEA, UN and UNEP. The group, which consists of one technical secretary from each of the international organizations mentioned and some 20 outside experts, is concerned with different aspects of the health of the marine environment. Normally, the group convenes once a year. Most of the business of GESAMP is carried out in working groups, but all reports have to be approved by GESAMP as a whole before publication. The work to be presented here is the result of evaluations carried out within Working Group 13 on 'Potentially Harmful Substances'. This work has been sponsored by IMO, WHO and UNEP. We have dealt with both hazards to living resources and hazards to human health. In this presentation only the human health aspects are discussed. We have made a thorough evaluation of six metals/metalloids, namely cadmium, lead, tin, arsenic, mercury and selenium. All the reports presented by the group have been approved by GESAMP; those for cadmium, lead and tin have already been published (GESAMP, 1985a), and those for arsenic, mercury and selenium will be published shortly (GESAMP, 1986a). Most of the work on possible carcinogenic risks is at the preliminary stage only and no detailed discussion has yet taken place within GESAMP. There is, however, general consensus that an evaluation of both the risks for living resources and for humans are of great importance. EVALUATION REPORTS
Cadmium, lead and tin In regard to cadmium, lead and tin, consumption of seafood does not generally constitute a serious toxicological problem. The contribution of seafood to the daily intake of these metals by humans is low. Under certain exceptional circumstances, however, cadmium may create a problem. Although low concentrations of cadmium are generally reported in fish meat, certain species of molluscs, scallops and oysters may have cadmium concentrations exceeding 1 mg/kg fresh weight. As a daily consumption level of only a couple of hundred micrograms of cadmium, over a period of many years of exposure, may increase cadmium concentrations in the critical organ in humans (the kidney) to toxic levels (Friberg et al., 1986a, b), it is possible to identify groups of people at increased risk. The daily intake of tin from seafood is only a small fraction of the total daily intake of tin. However, tin in fish and in other marine food products can be in the organic form. Organic tin may originate from anthropogenic sources, and/or from the synthesis of trimethyltin in the marine biota. In studies on experimental animals low doses of trimethyltin have produced irreversible damage of the central nervous
381
system (WHO, 1980a; Magos, 1986). At present it is not possible to predict whether, under certain exposure conditions, trimethyltin may present a hazard to human health. The reasons for this are twofold: (1) the lack of concentration data on marine food products; and (2) the lack of quantitative human toxicological data, on both toxic doses and clearance half-time.
Mercury An extensive review of mercury has been performed by GESAMP. The evaluation of human health aspects was based partly on Health Criteria Documents by WHO (WHO, 1976, 1980b) and on drafts of an updated Health Criteria Document on MeHg (methylmercury) which is currently being prepared by WHO. In the GESAMP report a number of other key articles used in the human health evaluation are listed, including Clarkson (1984), Clarkson et al. (1985) and Berlin (1986). Mercury, in the form of methylmercury (MeHg), is still considered a prime pollutant in fish, including marine fish. Its possible implications for human health are important and more and more emphasis is being put on the study of developmental effects, as observed in young children prenatally exposed to low concentrations of MeHg. It was estimated that in the most sensitive group of an adult population the earliest symptoms may appear following long-term daily ingestion of 200-500/zg Hg (as MeHg) for a 70-kg person (WHO, 1976). In 1972, FA O / WH O suggested a provisional tolerable weekly intake (PTWI) of 200/~g Hg (as MeHg) or 300 #g (as total Hg) for a 70-kg person (FAO/WHO, 1972). The PTWI for mercury has been reconfirmed (UNEP, 1980), but it was pointed out that 'there are indications that prenatal life is more sensitive to MeHg' and it was strongly recommended that 'further research be directed towards the recognition of any early health effects associated
TABLE I Daily intake of mercury as methylmercury via fish resulting from different combinations of fish cons u m p t i o n and methylmercury concentration in fish (from G E S A M P , 1986a). Concentration in fish (mg M e H g / k g ) 0.1 0.25 0.5 0.75 1.0 1.25 1.5
Intake (g fish/day) 20
40
60
100
150
300
1000
2 5 10 15 20 25 30
4 10 20 30 40 50 60
6 15 30 45 60 75 90
10 25 50 75 100 125 150
15 38 75 113 150 188 225
30 75 150 225 300 375 450
100 250 500 750 1000 1250 1500
382 with low levels of exposure'. According to a review by Clarkson et al. (1985), the fetus m a y be as much as 10 times more sensitive than the adult, but the response estimates for prenatal effects have wide confidence limits due to the small number o f children studied. Table I shows the daily intakes of M e H g that could be reached by different combinations of fish consumption and M e H g concentration in fish. The P T W I for adults (70 kg body weight) is equivalent to a M e H g intake of 30/zg H g / d a y . A separate P T W I has not yet been recommended for pregnant women but should, as discussed above, be set considerably lower. The mercury concentrations in fish presented in Table I are representative for sardine and cod (0.1 mg/kg), tuna fish (0.5 m g / k g ) and shark (1.0 mg/kg). In some species and in some areas concentrations may be considerably higher. The largest tuna fish in the Mediterranean have Hg concentrations of up to about 4 mg H g / k g fresh weight. Mercury concentrations in the muscle of shark species f r o m Mediterranean, South African and Australian coastal waters range f r o m 0.6 to 2.6/tg/g fresh weight. The consumption of seafood varies widely both between and within countries. Estimates of the average intake of fish have been carried out in a number of countries, but using various methods. Some data include both fish consumers and nonconsumers, other data are confined to fish consumers only. In some studies the form of seafood is defined and in very few instances the species are identified. The G E S A M P Working G r o u p has evaluated probable consumption habits in various countries (GESAMP, 1986a). Many of the published results indicate a consumption o f the order of 20 g / d a y (or about one seafood meal/week), but for several countries 60 g / d a y is more representative. It has been estimated that the world average fish consumption is approximately 16 g/day. For populations where the fish consumption distributions have been studied it has been estimated that the 97.5 percentile m a y be about 3 times the average ( W H O , 1985). F r o m Table I it can be seen that at this intake level the P T W I can be reached when MeHg concentrations in fish are lower than 0.75 m g / k g . Population groups consuming one normal fish m e a l / d a y (150 g fish) will reach the P T W I even when MeHg concentrations in the fish consumed are very low. For people who eat only one seafood meal per week (about 20 g fish/day), the P T W I will not be exceeded, even when the average MeHg concentration is very high. The P T W I for adults has a built-in safety factor of 10 from an intake (in adults) that has caused approximately a 5% prevalence of symptomatic MeHg poisoning. It is therefore not surprising that the relatively small-scale studies carried out so far fail to demonstrate health effects at intake levels only moderately higher than the P T W I . Even at a 10-times higher intake level one should expect only one affected case for every 20 studied (GESAMP, 1986a). It is concluded that there is a need for an international coordinated research approach to obtain the information necessary for governments and international
383 organizations to be able to develop valid guidelines to deal with the problem of MeHg in marine food. Such an international approach should include epidemiological studies of prenatally and postnatally exposed young children using agreed upon protocols for measuring effects on mental and physical development. Selenium Selenium will be dealt with only briefly. It is an essential element and may, at both low and high dietary intake levels, give rise to negative effects in humans (H6gberg and Alexander, 1986; WHO, 1986). Marine food, fish and shellfish contain considerable amounts of selenium and may therefore in deficient areas serve as a useful supplement to the dietary intake of selenium. Concentrations of selenium in seafood are not so high as to constitute a risk for toxic effects. According to a recent WHO evaluation (WHO, 1986) to increase blood selenium concentrations to an undesirably high level, selenium intake has to be in excess of 700/zg/day. GESAMP concludes that even the uninterrupted daily consumption of 1000 g seafood in the upper concentration range, around 1.5/zg/g, would bring daily consumption of selenium to a level only marginally higher than that considered to be the lower limit of undesirable exposure. The working group also discussed the interaction between selenium and mercury. Inorganic mercury and selenium form a stable mercuric-selenide complex. The equimolar occurrence of high concentrations of selenium and mercury in the liver of marine mammals is caused by the formation of biologically inert mercuric selenide. In contrast, however, bismethylmercury selenide, the complex formed between selenide and methylmercury is not stable. In animal experiments dietary selenium only delayed the onset of methylmercury intoxication. Arsenic From the toxicological point of view there are two forms of arsenic in marine organisms which should be considered, namely arsenobetaine, which is the dominant form in most seafood, and inorganic arsenic, which constitutes 2-10070 of the total arsenic content in seafood (WHO, 1981; Ishinishi et al., 1986). Inorganic arsenic is by far the most toxic form and has given rise to skin lesions, such as hyperkeratosis, hyperpigmentation and skin cancer, peripheral vascular disturbances including the so-called Blackfoot disease, effects on the central nervous system and chromosome damage. Inhalation of inorganic arsenic, both within industry and around arsenic-emitting industries, has given rise to lung cancer. Inorganic arsenic, primarily trivalent, but also pentavalent forms, must be considered to be toxicologically very potent. So far, the organic arsenic compounds present in seafood have not been shown to cause adverse health effects in man. A small number of studies, in which experimental animals have been exposed to a seafood
384
diet containing moderate levels of arsenic, have not revealed any overt signs of toxic effects. However, the consequences of lifelong intake of the organic arsenicals present in marine organisms are unknown. Seafood is the predominating source of human arsenic intake. To make possible a meaningful evaluation of the arsenic exposure from various types of seafood, both the inorganic and the organic arsenic components must be analyzed. This is of great importance when evaluating risks for the development of skin cancer. As a rule only total arsenic has been analyzed, but data on hand indicate that up to 10°70 of the arsenic in fish may be in the inorganic form (GESAMP, 1986a). In the W H O (1981) Health Criteria Document for Arsenic it was estimated that a total intake, from drinking water, of 10 g arsenic over a lifetime was related to a 5070 prevalence of arsenic-induced skin cancer. This would correspond to a daily intake of 0.4 mg inorganic arsenic over a lifetime, or a daily intake of 1 mg inorganic arsenic for about 25 yr. In the GESAMP review four levels o f seafood consumption have been evaluated, namely 20 g seafood/day (about one meal/wk), 60 g / d a y (three meals/wk), 150 g / d a y (one meal/day) and for the extreme consumer 1000 g/day. An estimation of the daily intake of inorganic and organic arsenic by consumers of various amounts and types of seafood, assuming different concentrations of arsenic in seafood and different relationships between inorganic and organic arsenic, is shown in Table II. It can be seen from Table II that a daily consumption of about 60 g seafood would correspond to a daily intake of 6-30 #g inorganic arsenic. Even 30/zg/day would be less than a 10th of the amount which according to the W H O Criteria Document would give rise to a 5070 increased risk for skin cancer after a lifetime. However, this amount may contribute significantly to the total daily intake of inorganic arsenic. In cases of extreme consumption of seafood, the intake of inorganic arsenic would reach levels at which the increased risk for skin cancer is definitely no longer negligible. In arriving at these estimates it has been assumed that the inorganic arsenic in TABLE II Total daily intake of inorganic and organic arsenic by consumers of various amounts and types of seafood (from GESAMP, 1986a). Mean concentration in seafood (gg As/g)
Consumption of seafood (g/day) 20 Inorg.
1.0a l0 b
2 10
60 Org. 18 190
Inorg. 6 30
150 Org. 54 570
1000
Inorg.
Org.
Inorg.
Org.
15 75
135 1425
100 500
900 9500
aNormal concentration in most commercially important fish species; 10% is assumed to be inorganic arsenic. bConcentration likely to be found in bottom feeding fish (e.g., flounder, sole) and in various crustacea; 5% is assumed to be inorganic arsenic.
385
seafood has the same bioavailability and toxicity as that in drinking water. Data concerning the toxicity of organic arsenic compounds are very scarce. There are no data at all concerning the toxicity for man. However, it seems likely that the toxicity of organic arsenic for man is much lower than that of inorganic arsenic. The few studies performed on experimental animals show that arsenic of marine origin gives rise to much lower tissue levels than does inorganic arsenic, and has a lower acute toxicity than inorganic arsenic. Considering the high concentration in certain food products consumed more or less daily by a large number of people and a tendency of organic arsenic to accumulate in, e.g., epididymis and testes, possible adverse health effects in man following long-term exposure need to be investigated. Further evaluations For arsenic what has been discussed above has also been discussed with and approved by GESAMP. Some further evaluations on arsenic have been made within the subgroup. Fishermen are probably exposed to arsenic via fish to a greater extent than are other groups of people and, therefore, if arsenic in seafood is carcinogenic, it is to be expected that this will show up as an increased incidence of skin cancer in this group. The problem is that fishermen are also exposed to UV light more often than most other population groups, a fact that makes causal evaluation difficult. There is one report from Spain (Cabre and Lasanta, 1968), in which an increased incidence o f malignant skin tumors has been reported for deep-sea fishermen and dockworkers on fishing wharves. The overall incidence was 170/1000 persons, compared to 71/1000 in the local population as a whole. Friberg and Norell (GESAMP, 1985b) studied the incidence of different cancer forms among marine fishermen living along the Swedish coastline. Information relating to occupation and cancer incidence has been made available through the Cancer Environment Register. This Swedish register was formed by record linkage between the 1960 Census and the 1961-79 Cancer Register (Swedish Cancer Environment Register, 1980). The 1960 Census in Sweden provides information on occupation, age, sex and domicile for a population of about 7.5 million. All cases of cancer diagnosed in this population can be obtained from the Swedish Cancer Register. Every inhabitant in Sweden has an individual identification number which is used in both registers. A total of 7225 marine fishermen aged 26-64 were identified in the 1960 Census. The reference group included all Swedish men, employed and between the ages of 20-64 (1960) and consisted of 2 million men. Cumulative incidences were calculated as the proportion of the 1960 Census population recorded in the Cancer Register 1961-79. Stratification was made by year of birth (5-yr groups) and county of domicile. To quantify the increase in risk, if ~my, the standardized morbidity ratio (SMR) was calculated as the observed number of cases divided by the expected number. Assessment of 90°7o confidence limits was performed according to Rothman and Boice (1979).
386 T A B L E III SMRs and cumulative incidence for cancer of the lip and s q u a m o u s carcinoma of the skin in Swedish marine fishermen, N = 7225 (ICD 7th revision) (from G E S A M P , 1985b). Cancer site
Lip cancer Skin cancer
N u m b e r of cases Observed
Expected
26 29
10.8 14.9
SMR
90O7o confidence limits
2.42 1.95
1.69-3.35 1.40-2.66
A high occurrence of lip cancer and of squamous carcinoma of the skin was found among fishermen (Table III). For most cancer sites the SMRs did not differ significantly from unity. SMR for melanoma was 1.30, but the 90°-/0 confidence limit had a lower value of 0.79. The location of the skin cancer (%) was: ear (24), face (48), neck (14), upper and lower limbs (10), unspecified (4). The corresponding location for Sweden as a whole (males) was; ear (27), face (33), neck (7), upper and lower limbs (16), trunk (6), unspecified (9). These findings are based on a record linkage, and the accuracy of data provided by the registers was checked in different ways. Comparing the Cancer Register with death certificates, the total loss of cases was estimated to be 3.4°70 (Mattson, 1977). Only 1.2070 of the persons registered in the Cancer Register were not identified in the Swedish 1960 Census (Wiklund et al., 1981). Random sample quality control disclosed that in the linkage between the Cancer Register and the 1960 Census 0.5°70 of the hits were inaccurate owing to incorrect personal identification numbers (Eklund and Wiklund, 1979). As there was reason to believe that the skin tumors found were related to exposure to UV light a comparison has been made with the occurrence of skin tumors found in two other occupational groups: agricultural workers and road-building workers, where exposure to sunlight is also considerable. The results are given in Table IV, and show that no similar relationship was found, although the SMR was slightly elevated.
T A B L E IV SMRs and cumulative incidence for squamous carcinoma of the skin in Swedish male workers in agriculture and road-building (from G E S A M P , 1985b). Occupation
Agriculture Road-building
N u m b e r of cases Observed
Expected
652 116
543 93
SMR
90o7o confidence limits
1.20 1.25
1.12-1.28 1.06-1.44
387 At a meeting of the working group held at IARC in L y o n in 1985 (GESAMP, 1986b), the following conclusions were reached: 'For arsenic some human data are available and these indicate that an increased risk of squamous carcinomas of the skin could be associated with high consumption of fish with high levels of inorganic arsenic. There is some epidemiological evidence of an increased incidence of squamous carcinoma of the skin in fishermen. It seems probable that one important cause of this increase is ultraviolet radiation from sunlight. Exposure to inorganic arsenic via seafood may have contributed to the increased incidence. However, there are no epidemiological data that support or deny the hypothesis of an association between arsenic intake via fish and cancer'.
Other carcinogenic substances Working Group 13 on 'Potentially Harmful Substances' has also considered possible carcinogenic risks of substances other than arsenic. This has been done in ad hoc subgroups and only a very brief discussion has taken place within GESAMP. One subgroup meeting took place at the International Agency for Research on Cancer (IARC), Lyon, France (GESAMP, 1986b), and another at the International Council for Exploration of the Sea (ICES), Copenhagen, Denmark (GESAMP, 1986c). A report (GESAMP, 1985b), prepared by the Chairman of Working Group 13, in cooperation with the IMO Technical Secretary of GESAMP and the advice of two outside experts, B.G. Bennet (UNEP/WHO) and D.C. Malins (National Oceanic Atmospheric Administration, Seattle, WA, U.S.A.), served as a basis for the discussions. IARC has listed more than 100 chemicals or complex mixtures, for which there is considered to be sufficient evidence of carcinogenicity in experimental animals. About 40 chemicals or groups of chemicals are considered carcinogenic or probably carcinogenic for humans. It is clear that there is much evidence that harmful, including carcinogenic, substances accumulate in fish, crustaceans and molluscs. The sources of these harmful substances could be 'natural' processes, general urban sewage pollution or specific industrial and agricultural pollution. For certain substances accumulation can be observed globally (e.g., arsenic and mercury), while for others (e.g., polyaromatic hydrocarbons) accumulation is limited to areas where local pollution occurs. In such areas concentrations of carcinogenic substances in marine organisms may reach levels several hundred times higher than in reference areas. This may be exemplified by results (Fig. 1) from a study by Malins et al. (1984) in which the summation values for PCBs in sediments and marine organisms from two areas of Puget Sound in Washington, U.S.A., were studied. A very high accumulation of PCBs (0.2-0.5/zg/g wet weight) was seen in a polluted area of the sound. A Swedish study showed mean PCB values of between 0.3-0.7 #g/g wet weight in herring from the Baltic (Andersson et al., 1984). An accumulation in marine organisms has also been observed for polyaromatic
388 ng/g wet weight
PCBs n
500400300200-
O
~ Sed Clam Crab Qurtermaster Harbor
Sed Clam Crab Fish Hylebos
Fig. 1. Concentrations (ppb) of PCBs in sediment and edible tissue of bottomfish, crab and clam (Malins et al., 1984).
hydrocarbons. It has, for example, been observed in the Chesapeake Bay in the U.S.A. that in a highly polluted area native oysters contain polyaromatic hydrocarbons at the-tens-of-ppm level (Malins, pers. comm.). In studies carried out in Puget Sound concentrations of aromatic hydrocarbons were very high in clams from a contaminated area, Hylebos (Fig. 2). Concentrations in fish were low, however, probably because fish can metabolize hydrocarbons (Varanasi et al., 1979; Varanasi and Gmur, 1981). In a recent Swedish study (Larsson, 1986) an estimate has been made of the contribution of various food groups in an average Swedish diet to the total dietary intake of a number of ng/g wet weight
I 8100
1000-
0 Sed Clam Crab
Sed Clam Crab Fish
Quartermaster Harbor
Hylebos
Fig. 2. Concentrations of 27 different aromatic hydrocarbons in sediment and edible tissue of bottomfish, crab and clam (D.C. Malins, pers. comm.).
389
~9 PAH=Flu, Py, BaA, Chr/Tri Bbf/Bjk, Bep, Bap, IPy
40"I" n O)
3 0 -_
I
"5 O
o
20-
HnnooHn
10-
h.
g O
.=
"~--
O
¢"
•J
o
'=
~
-~
0
~
O
•
0
Fig. 3. Estimated contribution of various food groupsmanaverage Swedish dietto the total dietary intake of fluoranthene, pyrene, benz(a)anthracene, chrysene/triphenylene, benzo(b)fluoranthene, benzo0)fluoranthene/benzo(k)fluoranthene, benzo(e)pyrene, benzo(a)pyrene, and indenol(l,2,3-cd)pyrene (Larsson, 1986).
polyaromatic hydrocarbons (Fig. 3). Cereals appear to be the principal contributor (about 34%0), followed by vegetables (about 18%) and oils and fats (about 16%). Smoked fish contributed only a few percent. The intake of cereals would, on an average, mean 330 ~g/person per year (Larsson, 1986). It is obvious when looking at Fig. 2 that already the consumption of 0.5-1 kg of clams/yr f r o m a polluted area will contribute considerably more. There seems to be very little data on concentrations in marine organisms for most of the chemicals classified by I A R C as 'associated' or 'highly probably associated' with cancer in humans, or for which there is considered to be sufficient evidence o f carcinogenicity in experimental animals. For certain key chemicals (e.g., dioxins, toxaphene, PCBs, D D T derivatives, other organo-halogens, benzo(a)pyrene, other hydrocarbons, arsenic, and certain other metals) data from different parts of the world are available. These data show that there can be a considerable accumulation in fish, shellfish and marine mammals. These data are seldom published in the open literature and are, therefore, not readily accessible. It is natural that the highest concentrations of carcinogens have usually been found close to point sources of pollution in harbors, estuaries and rivers but, as pointed out by the working group, elevated levels of carcinogens have also been reported in some large confined waters (e.g., the Baltic, Mediterranean, North American Great Lakes). In these waters the reported levels in marine organisms are a b o u t 10 times higher than those in the open seas of the North Atlantic or the North Pacific.
390
RISK ASSESSMENT
Risk assessments based on concentrations of carcinogenic substances in marine organisms used as food have, with few exceptions, not been carried out. However, in the preparation of an Environmental Health Criteria Document (WHO, 1981) risk assessment procedures were used for arsenic in water. If the bioavailability of inorganic arsenic in food is the same as that for arsenic in water, the available data indicate that an increased risk of squamous carcinomas of the skin can be associated with high consumption of fish which contains high levels of inorganic arsenic. Risk assessments have been made also for PCBs in fish (Cordle et al., 1982). This assessment was based on animal experimental data, which makes the findings more uncertain. The estimation indicates that, based on a nonthreshold model, an increased risk of cancer can be caused by the consumption of fish containing high levels of PCBs. During the evaluation within Working Group 13 it was found that there were several studies where liver tumors a n d / o r skin papillomas had been produced experimentally in fish. Furthermore, a number of field studies in several areas of the world report such tumors. It was recognized, however, that there are great difficulties in carrying out systematic tumor studies of fish using epidemiological methods. In order to utilize existing fish survey resources effectively, an international cooperative multidisciplinary p r o g r a m is needed, involving fish ecologists, fish pathologists, h u m a n epidemiologists, toxicologists and analytical chemists ( G E S A M P , 1986c). There is a lack of epidemiological data with focus directly on the risks for humans. Dietary factors are most probably a m a j o r causative element in the etiology of h u m a n cancers (see, e.g., Doll and Peto, 1981; Swedish Cancer Committee, 1984). The role of industrial chemical contamination of food has not been determined. In spite of the existence of a large number of studies on the association between diet and cancer, consumption of seafood in the etiology of h u m a n cancer has only rarely been considered. RECOMMENDATIONS
Based on the reviews and evaluations carried out so far a recommendation has been submitted to G E S A M P to the effect that 'the organizations concerned consider, as a matter of urgency, the mobilization of the necessary support for the further development and acceleration of work on the Impact of Carcinogenic Substances on Marine Organisms and Implications concerning Public Health'. At the last review meeting (GESAMP, 1986c) the above recommendation was formulated as a need to carry out comprehensive reviews and evaluations of all aspects of the hazards of carcinogens in the marine environment. Such studies should cover fish, invertebrates, marine birds, m a m m a l s as well as risks for humans. A detailed
391 review o f h u m a n fish c o n s u m p t i o n p a t t e r n s should be i n c l u d e d as well as the p a t h w a y s for carcinogens via fish meals. It was recognized that the work p r o p o s e d will be time c o n s u m i n g , will need to use a m u l t i d i s c i p l i n a r y a p p r o a c h a n d involve specialists in several fields. F u l l - t i m e s u p p o r t staff a n d other resources will be needed for a m i n i m u m period of a b o u t 3 yr. It was p o i n t e d o u t that such a review m u s t f o r m the scientific basis for a n y evaluat i o n s o f the ' s a f e t y ' or p e r c e p t i o n of ' s a f e t y ' o f c o n s u m p t i o n o f fish f r o m different parts o f the world a n d will, therefore, be o f key i m p o r t a n c e for the c o m m e r c i a l a n d sport fisheries. T h e p r o b l e m o f how a n d w h e n tO proceed is, to a great extent, o f a financial n a t u r e . A n y t h o r o u g h e v a l u a t i o n , even w i t h o u t i n v e s t m e n t s for new research, w o u l d need s u b s t a n t i a l e c o n o m i c s u p p o r t . As m e n t i o n e d in the i n t r o d u c t i o n G E S A M P has recognized the potential severity o f the p r o b l e m as well as the diversity a n d complexity o f the subject, i.e., a dual focus o n the occurrence o f t u m o r s in fish as well as o n h u m a n carcinogenicity related to seafood c o n s u m p t i o n . A considerable interest has been expressed also by the L o n d o n D u m p i n g C o n v e n t i o n a n d the Oslo C o m m i s s i o n . F o r the time being n o special f u n d s have been e a r m a r k e d for further work in the field. It is expected that the C h a i r m a n o f the W o r k i n g G r o u p at the next meeting o f G E S A M P , M a r c h 1987, will report o n possibilities o f o b t a i n i n g external s u p p o r t for further work.
REFERENCES Andersson, O., C.-E. Linder and R. Vaz, 1984. Levels of organochlorine pesticides, PCBs and certain other organohalogen compounds in fishery products in Sweden, 1976-1982. V~r F6da 36, Suppl. 1. Berlin, M., 1986. Mercury. In: Handbook on the toxicology of metals, Vol. II, edited by L. Friberg, G.F. Nordberg and V.B. Vouk, Elsevier, Amsterdam, pp. 387-445. Cabre, J. and J. Lasanta, 1968. Malignant epithelial tumors in deep-sea fishermen. Actas DermoSifiliogr. 59, 361-364. Clarkson, T.W., 1984. Mercury. In: Changing metal cycles and human health, edited by J.O. Nriagu, Dahlem Workshop Reports, Life Science Reports, Berlin, Vol. 28. Clarkson, T.W., G.F. Nordberg and P.R. Sager, 1985. Reproductive and developmental toxicity of metals. Scand. J. Work Environ. Health 11, 145-154. Cordle, F., R. Locke and J. Springer, 1982. Risk assessment in a federal regulatory agency: an assessment of risk associated with the human consumption of some species of fish contaminated with polychlorinated biphenyls (PCBs). Environ. Health Perspect. 45, 171-182. Doll, R. and R. Peto, 1981. The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J. Nat. Cancer Inst. 66, 1191-1308. Eklund, G. and K. Wiklund, 1979. Quality control study of the personal identity in the cancer environment registry. Stat. Rev., Third SeE, Vol. 17, 373-376; 407-408. Nat. Swed. Cent. Bur. Star., Stockholm. FAO/WHO, 1972. Evaluation of certain food additives and the contaminants mercury, lead and cadmium. WHO Tech. Rep. Ser. 505.
392 Friberg, L., T. Kjellstr6m and G.F. Nordberg, 1986a. Cadmium. In: Handbook on the toxicology of metals, Vol. II, edited by L. Friberg, G.F. Nordberg and V.B. Vouk, Elsevier, Amsterdam, pp. 130-184. Friberg, L., C.-G. Elinder, T. Kjellstr6m and G.F. Nordberg, eds., 1986b. Cadmium and health: a toxicological and epidemiological appraisal, Vols. I, II, CRC Press, Boca Raton, FL, 209, 307 pp. GESAMP, 1985a. Review of potentially harmful substances - cadmium, lead and tin. WHO Rep. Stud. 22, Geneva. GESAMP, 1985b. The impact of carcinogenic substances on marine organisms and implications concerning public health, GESAMP XV/2/4. WHO Intern. Rep, Geneva. GESAMP, 1986a. Review of potentially harmful substances - arsenic, mercury and selenium, WHO Rep. Stud. 28, Geneva. GESAMP, 1986b. Impact of carcinogenic substances on marine organisms and implications concerning public health, GESAMP XVI/2/3. WHO Intern. Rep, Geneva. GESAMP, 1986c. Occurrence of potential carcinogens and tumours in marine organisms, GESAMP XVI/2/4. WHO Intern. Rep, Geneva. H6gberg, J. and J. Alexander, 1986. Selenium. In: Handbook on the toxicology of metals, Vol. If, edited by L. Friberg, G.F. Nordberg and V.B. Vouk, Elsevier, Amsterdam, pp. 482-520. Ishinishi, N., K. Tsuchiya, M. Vahter and B.A. Fowler, 1986. Arsenic. In: Handbook on the toxicology of metals, Vol. II, edited by L. Friberg, G.F. Nordberg and V.B. Vouk, Elsevier, Amsterdam, pp. 43-83. Larsson, B., 1986. Polycyclic aromatic hydrocarbons in Swedish foods. Aspects on analysis, occurrence and intake. Doctoral thesis, Swedish University of Agricultural Sciences, Uppsala. Magos, L., 1986. Tin. In: Handbook on the toxicology of metals, Vol. II, edited by L. Friberg, G.F. Nordberg and V.B. Vouk, Elsevier, Amsterdam, pp. 568-593. Malins, D.C., B.B. McCain, D.W. Brown, S.-L. Chan, M.S. Myers, J.T. Landahl, P.G. Prohaska, A.J. Friedman, L.D. Rhodes, D.G. Burrows, W.D. Gronlund and H.O. Hodgins, 1984. Chemical pollutants in sediments and diseases of bottom-dwelling fish in Puget Sound, Washington. Environ. Sci. Technol. 18, 705-713. Mattson, B., 1977. Completeness of registration in the Swedish Cancer Registry. Stat. Rep. HS 1977, 12. Nat. Swed. Cent. Bur. Stat., Stockholm. Rothman, J.J. and J.D. Boice, 1979. Epidemiologic analysis with a programmable calculator. DHEW Publ. (NIH) 79-1649, U.S. Government Printing Office, Washington, DC. Swedish Cancer Committee, 1984. Cancer - causes - prevention, etc. SOU 1984, 67. Minis. Health Soc. Aff., Stockholm. Swedish Cancer Environment Register, 1980. National Board of Health and Welfare Committee for the Cancer Environment Register in collaboration with the National Swedish Central Bureau of Statistics and the Swedish Work Environment Fund, Stockholm. UNEP, 1980. Report of the UNEP/FAO/WHO meeting of experts on environmental quality criteria for mercury in Mediterranean seafood. Rep. UNEP/MED-HG/14, UN Environ. Program., Nairobi, 19 PP. Varanasi, U. and D.J. Gmur, 1981. Hydrocarbons and metabolites in English sole (Parophrys vetulus) exposed simultaneously to (3H)benzo(a)-pyrene and (14C)naphthalene in oil-contaminated sediment. Aquat. Toxicol. 1, 49. Varanasi, U., D.J. Gmur and P.A. Treseler, 1979. Influence of time and mode of exposure on biotransformation of naphthalene by juvenile starry flounder (Platchthys stellatus) and rock sole (Lepidopsetta bilineata). Arch. Environ. Contam. Toxicol. 8, 673-692. WHO, 1976. Environmental health criteria 1. Mercury. WHO, Geneva, 132 pp. WHO, 1980a. Environmental health criteria 15. Tin and organotin compounds. WHO, Geneva, 109 pp. WHO, 1980b. Consultation to re-examine the WHO environmental health criteria for mercury. EHE/EHC/80.22, WHO Geneva Intern. Rep., 18 pp.
393 WHO, 1981. Environmental health criteria 18. Arsenic. WHO, Geneva, 174 pp. WHO, 1985. Guidelines for the study of dietary intakes of chemical contaminants, GEMS. WHO Offset Publ. 87, Geneva. WHO, 1986. Environmental health criteria. Selenium. WHO, Geneva, in press. Wiklund, K., J. Einhorn and G. Wennerstrfm, 1981. Swedish cancer environment register available for research. Scand. J. Work Environ. Health 7, 64-67.
379
Elsevier
A Q T 00303
The GESAMP evaluation of potentially harmful substances in fish and other seafood with special reference to carcinogenic substances Lars Friberg* Department of Environmental Hygiene, Karolinska Institute, Stockholm, Sweden; National Institute of Environmental Medicine, Stockholm, Sweden (Received 16 September 1986; accepted 15 April 1987)
The
joint
Group
of
Experts
on
the Scientific
Aspects
of
Marine
Pollution,
GESAMP
(IMO/FAO/UNESCO/WMO/WHO/IAEA/UN/UNEP), has evaluated two groups of metals, (1) cadm i u m , lead and tin, and (2) arsenic, mercury and selenium, and has preliminarily discussed risks for carcinogenic effects arising from pollutants. These evaluations are based on work carried out within the G E S A M P Working Group 13 and cover hazards to living resources as well as to h u m a n health. In this presentation only the h u m a n health aspects are discussed. Only under exceptional circumstances will c a d m i u m intake from fish constitute an important part of the total daily intake via food. High consumption of certain shellfish may considerably increase the intake. Lead in seafood does not greatly contribute to the daily intake of lead. The contribution o f seafood to the daily intake of tin is low. However, more data are needed for trimethyltin. Exposure to arsenic via seafood m a y be substantial. Most of this arsenic is in the form of arsenobetaine, which is considered relatively atoxic. Extreme seafood consumption m a y give rise to an intake of several hundred micrograms of inorganic arsenic per day; an exposure level which over a lifetime m a y be related to a significant increase in skin cancer. Groups with high fish intake or intake of fish with a high methylmercury content can easily exceed the W H O / F A O provisional tolerable intake level. Pregnant women constitute a special risk group. A coordinated research approach on an international basis is needed to obtain the necessary data to establish valid guidelines. Selenium does not pose a toxicological problem. Its importance as related to different mercury c o m p o u n d s is discussed. Preliminary evaluations of the risks for carcinogenic effects have been carried out, partly in collaboration with the W H O International Agency for Research on Cancer. Taking all the evidence into account it was considered as a matter o f urgency to mobilize the necessary support for the further development and acceleration of work on the impact of carcinogenic substances on marine organisms and the implications for public health. Key words: Marine pollution; Cancer; G E S A M P ; Mercury; Arsenic; PCB; Hydrocarbons Presented at the Symposium "Toxic Chemicals and Aquatic Life: Research and M a n a g e m e n t " , September 16-18, 1986, Seattle, Washington, U.S.A.
Correspondence to: L. Friberg, National Institute of Environmental Medicine, 104 01 Stockholm, Sweden. * C h a i r m a n of the G E S A M P Working Group 13. 0166-445X/88/$ 03.50 © 1988 Elsevier Science Publishers B.V. (Biomedical Division)
380 INTRODUCTION
GESAMP, the joint Group of Experts on the Scientific Aspects of Marine Pollution, is an international body sponsored by several international organizations, IMO, FAO, UNESCO, WMO, WHO, IAEA, UN and UNEP. The group, which consists of one technical secretary from each of the international organizations mentioned and some 20 outside experts, is concerned with different aspects of the health of the marine environment. Normally, the group convenes once a year. Most of the business of GESAMP is carried out in working groups, but all reports have to be approved by GESAMP as a whole before publication. The work to be presented here is the result of evaluations carried out within Working Group 13 on 'Potentially Harmful Substances'. This work has been sponsored by IMO, WHO and UNEP. We have dealt with both hazards to living resources and hazards to human health. In this presentation only the human health aspects are discussed. We have made a thorough evaluation of six metals/metalloids, namely cadmium, lead, tin, arsenic, mercury and selenium. All the reports presented by the group have been approved by GESAMP; those for cadmium, lead and tin have already been published (GESAMP, 1985a), and those for arsenic, mercury and selenium will be published shortly (GESAMP, 1986a). Most of the work on possible carcinogenic risks is at the preliminary stage only and no detailed discussion has yet taken place within GESAMP. There is, however, general consensus that an evaluation of both the risks for living resources and for humans are of great importance. EVALUATION REPORTS
Cadmium, lead and tin In regard to cadmium, lead and tin, consumption of seafood does not generally constitute a serious toxicological problem. The contribution of seafood to the daily intake of these metals by humans is low. Under certain exceptional circumstances, however, cadmium may create a problem. Although low concentrations of cadmium are generally reported in fish meat, certain species of molluscs, scallops and oysters may have cadmium concentrations exceeding 1 mg/kg fresh weight. As a daily consumption level of only a couple of hundred micrograms of cadmium, over a period of many years of exposure, may increase cadmium concentrations in the critical organ in humans (the kidney) to toxic levels (Friberg et al., 1986a, b), it is possible to identify groups of people at increased risk. The daily intake of tin from seafood is only a small fraction of the total daily intake of tin. However, tin in fish and in other marine food products can be in the organic form. Organic tin may originate from anthropogenic sources, and/or from the synthesis of trimethyltin in the marine biota. In studies on experimental animals low doses of trimethyltin have produced irreversible damage of the central nervous
381
system (WHO, 1980a; Magos, 1986). At present it is not possible to predict whether, under certain exposure conditions, trimethyltin may present a hazard to human health. The reasons for this are twofold: (1) the lack of concentration data on marine food products; and (2) the lack of quantitative human toxicological data, on both toxic doses and clearance half-time.
Mercury An extensive review of mercury has been performed by GESAMP. The evaluation of human health aspects was based partly on Health Criteria Documents by WHO (WHO, 1976, 1980b) and on drafts of an updated Health Criteria Document on MeHg (methylmercury) which is currently being prepared by WHO. In the GESAMP report a number of other key articles used in the human health evaluation are listed, including Clarkson (1984), Clarkson et al. (1985) and Berlin (1986). Mercury, in the form of methylmercury (MeHg), is still considered a prime pollutant in fish, including marine fish. Its possible implications for human health are important and more and more emphasis is being put on the study of developmental effects, as observed in young children prenatally exposed to low concentrations of MeHg. It was estimated that in the most sensitive group of an adult population the earliest symptoms may appear following long-term daily ingestion of 200-500/zg Hg (as MeHg) for a 70-kg person (WHO, 1976). In 1972, FA O / WH O suggested a provisional tolerable weekly intake (PTWI) of 200/~g Hg (as MeHg) or 300 #g (as total Hg) for a 70-kg person (FAO/WHO, 1972). The PTWI for mercury has been reconfirmed (UNEP, 1980), but it was pointed out that 'there are indications that prenatal life is more sensitive to MeHg' and it was strongly recommended that 'further research be directed towards the recognition of any early health effects associated
TABLE I Daily intake of mercury as methylmercury via fish resulting from different combinations of fish cons u m p t i o n and methylmercury concentration in fish (from G E S A M P , 1986a). Concentration in fish (mg M e H g / k g ) 0.1 0.25 0.5 0.75 1.0 1.25 1.5
Intake (g fish/day) 20
40
60
100
150
300
1000
2 5 10 15 20 25 30
4 10 20 30 40 50 60
6 15 30 45 60 75 90
10 25 50 75 100 125 150
15 38 75 113 150 188 225
30 75 150 225 300 375 450
100 250 500 750 1000 1250 1500
382 with low levels of exposure'. According to a review by Clarkson et al. (1985), the fetus m a y be as much as 10 times more sensitive than the adult, but the response estimates for prenatal effects have wide confidence limits due to the small number o f children studied. Table I shows the daily intakes of M e H g that could be reached by different combinations of fish consumption and M e H g concentration in fish. The P T W I for adults (70 kg body weight) is equivalent to a M e H g intake of 30/zg H g / d a y . A separate P T W I has not yet been recommended for pregnant women but should, as discussed above, be set considerably lower. The mercury concentrations in fish presented in Table I are representative for sardine and cod (0.1 mg/kg), tuna fish (0.5 m g / k g ) and shark (1.0 mg/kg). In some species and in some areas concentrations may be considerably higher. The largest tuna fish in the Mediterranean have Hg concentrations of up to about 4 mg H g / k g fresh weight. Mercury concentrations in the muscle of shark species f r o m Mediterranean, South African and Australian coastal waters range f r o m 0.6 to 2.6/tg/g fresh weight. The consumption of seafood varies widely both between and within countries. Estimates of the average intake of fish have been carried out in a number of countries, but using various methods. Some data include both fish consumers and nonconsumers, other data are confined to fish consumers only. In some studies the form of seafood is defined and in very few instances the species are identified. The G E S A M P Working G r o u p has evaluated probable consumption habits in various countries (GESAMP, 1986a). Many of the published results indicate a consumption o f the order of 20 g / d a y (or about one seafood meal/week), but for several countries 60 g / d a y is more representative. It has been estimated that the world average fish consumption is approximately 16 g/day. For populations where the fish consumption distributions have been studied it has been estimated that the 97.5 percentile m a y be about 3 times the average ( W H O , 1985). F r o m Table I it can be seen that at this intake level the P T W I can be reached when MeHg concentrations in fish are lower than 0.75 m g / k g . Population groups consuming one normal fish m e a l / d a y (150 g fish) will reach the P T W I even when MeHg concentrations in the fish consumed are very low. For people who eat only one seafood meal per week (about 20 g fish/day), the P T W I will not be exceeded, even when the average MeHg concentration is very high. The P T W I for adults has a built-in safety factor of 10 from an intake (in adults) that has caused approximately a 5% prevalence of symptomatic MeHg poisoning. It is therefore not surprising that the relatively small-scale studies carried out so far fail to demonstrate health effects at intake levels only moderately higher than the P T W I . Even at a 10-times higher intake level one should expect only one affected case for every 20 studied (GESAMP, 1986a). It is concluded that there is a need for an international coordinated research approach to obtain the information necessary for governments and international
383 organizations to be able to develop valid guidelines to deal with the problem of MeHg in marine food. Such an international approach should include epidemiological studies of prenatally and postnatally exposed young children using agreed upon protocols for measuring effects on mental and physical development. Selenium Selenium will be dealt with only briefly. It is an essential element and may, at both low and high dietary intake levels, give rise to negative effects in humans (H6gberg and Alexander, 1986; WHO, 1986). Marine food, fish and shellfish contain considerable amounts of selenium and may therefore in deficient areas serve as a useful supplement to the dietary intake of selenium. Concentrations of selenium in seafood are not so high as to constitute a risk for toxic effects. According to a recent WHO evaluation (WHO, 1986) to increase blood selenium concentrations to an undesirably high level, selenium intake has to be in excess of 700/zg/day. GESAMP concludes that even the uninterrupted daily consumption of 1000 g seafood in the upper concentration range, around 1.5/zg/g, would bring daily consumption of selenium to a level only marginally higher than that considered to be the lower limit of undesirable exposure. The working group also discussed the interaction between selenium and mercury. Inorganic mercury and selenium form a stable mercuric-selenide complex. The equimolar occurrence of high concentrations of selenium and mercury in the liver of marine mammals is caused by the formation of biologically inert mercuric selenide. In contrast, however, bismethylmercury selenide, the complex formed between selenide and methylmercury is not stable. In animal experiments dietary selenium only delayed the onset of methylmercury intoxication. Arsenic From the toxicological point of view there are two forms of arsenic in marine organisms which should be considered, namely arsenobetaine, which is the dominant form in most seafood, and inorganic arsenic, which constitutes 2-10070 of the total arsenic content in seafood (WHO, 1981; Ishinishi et al., 1986). Inorganic arsenic is by far the most toxic form and has given rise to skin lesions, such as hyperkeratosis, hyperpigmentation and skin cancer, peripheral vascular disturbances including the so-called Blackfoot disease, effects on the central nervous system and chromosome damage. Inhalation of inorganic arsenic, both within industry and around arsenic-emitting industries, has given rise to lung cancer. Inorganic arsenic, primarily trivalent, but also pentavalent forms, must be considered to be toxicologically very potent. So far, the organic arsenic compounds present in seafood have not been shown to cause adverse health effects in man. A small number of studies, in which experimental animals have been exposed to a seafood
384
diet containing moderate levels of arsenic, have not revealed any overt signs of toxic effects. However, the consequences of lifelong intake of the organic arsenicals present in marine organisms are unknown. Seafood is the predominating source of human arsenic intake. To make possible a meaningful evaluation of the arsenic exposure from various types of seafood, both the inorganic and the organic arsenic components must be analyzed. This is of great importance when evaluating risks for the development of skin cancer. As a rule only total arsenic has been analyzed, but data on hand indicate that up to 10°70 of the arsenic in fish may be in the inorganic form (GESAMP, 1986a). In the W H O (1981) Health Criteria Document for Arsenic it was estimated that a total intake, from drinking water, of 10 g arsenic over a lifetime was related to a 5070 prevalence of arsenic-induced skin cancer. This would correspond to a daily intake of 0.4 mg inorganic arsenic over a lifetime, or a daily intake of 1 mg inorganic arsenic for about 25 yr. In the GESAMP review four levels o f seafood consumption have been evaluated, namely 20 g seafood/day (about one meal/wk), 60 g / d a y (three meals/wk), 150 g / d a y (one meal/day) and for the extreme consumer 1000 g/day. An estimation of the daily intake of inorganic and organic arsenic by consumers of various amounts and types of seafood, assuming different concentrations of arsenic in seafood and different relationships between inorganic and organic arsenic, is shown in Table II. It can be seen from Table II that a daily consumption of about 60 g seafood would correspond to a daily intake of 6-30 #g inorganic arsenic. Even 30/zg/day would be less than a 10th of the amount which according to the W H O Criteria Document would give rise to a 5070 increased risk for skin cancer after a lifetime. However, this amount may contribute significantly to the total daily intake of inorganic arsenic. In cases of extreme consumption of seafood, the intake of inorganic arsenic would reach levels at which the increased risk for skin cancer is definitely no longer negligible. In arriving at these estimates it has been assumed that the inorganic arsenic in TABLE II Total daily intake of inorganic and organic arsenic by consumers of various amounts and types of seafood (from GESAMP, 1986a). Mean concentration in seafood (gg As/g)
Consumption of seafood (g/day) 20 Inorg.
1.0a l0 b
2 10
60 Org. 18 190
Inorg. 6 30
150 Org. 54 570
1000
Inorg.
Org.
Inorg.
Org.
15 75
135 1425
100 500
900 9500
aNormal concentration in most commercially important fish species; 10% is assumed to be inorganic arsenic. bConcentration likely to be found in bottom feeding fish (e.g., flounder, sole) and in various crustacea; 5% is assumed to be inorganic arsenic.
385
seafood has the same bioavailability and toxicity as that in drinking water. Data concerning the toxicity of organic arsenic compounds are very scarce. There are no data at all concerning the toxicity for man. However, it seems likely that the toxicity of organic arsenic for man is much lower than that of inorganic arsenic. The few studies performed on experimental animals show that arsenic of marine origin gives rise to much lower tissue levels than does inorganic arsenic, and has a lower acute toxicity than inorganic arsenic. Considering the high concentration in certain food products consumed more or less daily by a large number of people and a tendency of organic arsenic to accumulate in, e.g., epididymis and testes, possible adverse health effects in man following long-term exposure need to be investigated. Further evaluations For arsenic what has been discussed above has also been discussed with and approved by GESAMP. Some further evaluations on arsenic have been made within the subgroup. Fishermen are probably exposed to arsenic via fish to a greater extent than are other groups of people and, therefore, if arsenic in seafood is carcinogenic, it is to be expected that this will show up as an increased incidence of skin cancer in this group. The problem is that fishermen are also exposed to UV light more often than most other population groups, a fact that makes causal evaluation difficult. There is one report from Spain (Cabre and Lasanta, 1968), in which an increased incidence o f malignant skin tumors has been reported for deep-sea fishermen and dockworkers on fishing wharves. The overall incidence was 170/1000 persons, compared to 71/1000 in the local population as a whole. Friberg and Norell (GESAMP, 1985b) studied the incidence of different cancer forms among marine fishermen living along the Swedish coastline. Information relating to occupation and cancer incidence has been made available through the Cancer Environment Register. This Swedish register was formed by record linkage between the 1960 Census and the 1961-79 Cancer Register (Swedish Cancer Environment Register, 1980). The 1960 Census in Sweden provides information on occupation, age, sex and domicile for a population of about 7.5 million. All cases of cancer diagnosed in this population can be obtained from the Swedish Cancer Register. Every inhabitant in Sweden has an individual identification number which is used in both registers. A total of 7225 marine fishermen aged 26-64 were identified in the 1960 Census. The reference group included all Swedish men, employed and between the ages of 20-64 (1960) and consisted of 2 million men. Cumulative incidences were calculated as the proportion of the 1960 Census population recorded in the Cancer Register 1961-79. Stratification was made by year of birth (5-yr groups) and county of domicile. To quantify the increase in risk, if ~my, the standardized morbidity ratio (SMR) was calculated as the observed number of cases divided by the expected number. Assessment of 90°7o confidence limits was performed according to Rothman and Boice (1979).
386 T A B L E III SMRs and cumulative incidence for cancer of the lip and s q u a m o u s carcinoma of the skin in Swedish marine fishermen, N = 7225 (ICD 7th revision) (from G E S A M P , 1985b). Cancer site
Lip cancer Skin cancer
N u m b e r of cases Observed
Expected
26 29
10.8 14.9
SMR
90O7o confidence limits
2.42 1.95
1.69-3.35 1.40-2.66
A high occurrence of lip cancer and of squamous carcinoma of the skin was found among fishermen (Table III). For most cancer sites the SMRs did not differ significantly from unity. SMR for melanoma was 1.30, but the 90°-/0 confidence limit had a lower value of 0.79. The location of the skin cancer (%) was: ear (24), face (48), neck (14), upper and lower limbs (10), unspecified (4). The corresponding location for Sweden as a whole (males) was; ear (27), face (33), neck (7), upper and lower limbs (16), trunk (6), unspecified (9). These findings are based on a record linkage, and the accuracy of data provided by the registers was checked in different ways. Comparing the Cancer Register with death certificates, the total loss of cases was estimated to be 3.4°70 (Mattson, 1977). Only 1.2070 of the persons registered in the Cancer Register were not identified in the Swedish 1960 Census (Wiklund et al., 1981). Random sample quality control disclosed that in the linkage between the Cancer Register and the 1960 Census 0.5°70 of the hits were inaccurate owing to incorrect personal identification numbers (Eklund and Wiklund, 1979). As there was reason to believe that the skin tumors found were related to exposure to UV light a comparison has been made with the occurrence of skin tumors found in two other occupational groups: agricultural workers and road-building workers, where exposure to sunlight is also considerable. The results are given in Table IV, and show that no similar relationship was found, although the SMR was slightly elevated.
T A B L E IV SMRs and cumulative incidence for squamous carcinoma of the skin in Swedish male workers in agriculture and road-building (from G E S A M P , 1985b). Occupation
Agriculture Road-building
N u m b e r of cases Observed
Expected
652 116
543 93
SMR
90o7o confidence limits
1.20 1.25
1.12-1.28 1.06-1.44
387 At a meeting of the working group held at IARC in L y o n in 1985 (GESAMP, 1986b), the following conclusions were reached: 'For arsenic some human data are available and these indicate that an increased risk of squamous carcinomas of the skin could be associated with high consumption of fish with high levels of inorganic arsenic. There is some epidemiological evidence of an increased incidence of squamous carcinoma of the skin in fishermen. It seems probable that one important cause of this increase is ultraviolet radiation from sunlight. Exposure to inorganic arsenic via seafood may have contributed to the increased incidence. However, there are no epidemiological data that support or deny the hypothesis of an association between arsenic intake via fish and cancer'.
Other carcinogenic substances Working Group 13 on 'Potentially Harmful Substances' has also considered possible carcinogenic risks of substances other than arsenic. This has been done in ad hoc subgroups and only a very brief discussion has taken place within GESAMP. One subgroup meeting took place at the International Agency for Research on Cancer (IARC), Lyon, France (GESAMP, 1986b), and another at the International Council for Exploration of the Sea (ICES), Copenhagen, Denmark (GESAMP, 1986c). A report (GESAMP, 1985b), prepared by the Chairman of Working Group 13, in cooperation with the IMO Technical Secretary of GESAMP and the advice of two outside experts, B.G. Bennet (UNEP/WHO) and D.C. Malins (National Oceanic Atmospheric Administration, Seattle, WA, U.S.A.), served as a basis for the discussions. IARC has listed more than 100 chemicals or complex mixtures, for which there is considered to be sufficient evidence of carcinogenicity in experimental animals. About 40 chemicals or groups of chemicals are considered carcinogenic or probably carcinogenic for humans. It is clear that there is much evidence that harmful, including carcinogenic, substances accumulate in fish, crustaceans and molluscs. The sources of these harmful substances could be 'natural' processes, general urban sewage pollution or specific industrial and agricultural pollution. For certain substances accumulation can be observed globally (e.g., arsenic and mercury), while for others (e.g., polyaromatic hydrocarbons) accumulation is limited to areas where local pollution occurs. In such areas concentrations of carcinogenic substances in marine organisms may reach levels several hundred times higher than in reference areas. This may be exemplified by results (Fig. 1) from a study by Malins et al. (1984) in which the summation values for PCBs in sediments and marine organisms from two areas of Puget Sound in Washington, U.S.A., were studied. A very high accumulation of PCBs (0.2-0.5/zg/g wet weight) was seen in a polluted area of the sound. A Swedish study showed mean PCB values of between 0.3-0.7 #g/g wet weight in herring from the Baltic (Andersson et al., 1984). An accumulation in marine organisms has also been observed for polyaromatic
388 ng/g wet weight
PCBs n
500400300200-
O
~ Sed Clam Crab Qurtermaster Harbor
Sed Clam Crab Fish Hylebos
Fig. 1. Concentrations (ppb) of PCBs in sediment and edible tissue of bottomfish, crab and clam (Malins et al., 1984).
hydrocarbons. It has, for example, been observed in the Chesapeake Bay in the U.S.A. that in a highly polluted area native oysters contain polyaromatic hydrocarbons at the-tens-of-ppm level (Malins, pers. comm.). In studies carried out in Puget Sound concentrations of aromatic hydrocarbons were very high in clams from a contaminated area, Hylebos (Fig. 2). Concentrations in fish were low, however, probably because fish can metabolize hydrocarbons (Varanasi et al., 1979; Varanasi and Gmur, 1981). In a recent Swedish study (Larsson, 1986) an estimate has been made of the contribution of various food groups in an average Swedish diet to the total dietary intake of a number of ng/g wet weight
I 8100
1000-
0 Sed Clam Crab
Sed Clam Crab Fish
Quartermaster Harbor
Hylebos
Fig. 2. Concentrations of 27 different aromatic hydrocarbons in sediment and edible tissue of bottomfish, crab and clam (D.C. Malins, pers. comm.).
389
~9 PAH=Flu, Py, BaA, Chr/Tri Bbf/Bjk, Bep, Bap, IPy
40"I" n O)
3 0 -_
I
"5 O
o
20-
HnnooHn
10-
h.
g O
.=
"~--
O
¢"
•J
o
'=
~
-~
0
~
O
•
0
Fig. 3. Estimated contribution of various food groupsmanaverage Swedish dietto the total dietary intake of fluoranthene, pyrene, benz(a)anthracene, chrysene/triphenylene, benzo(b)fluoranthene, benzo0)fluoranthene/benzo(k)fluoranthene, benzo(e)pyrene, benzo(a)pyrene, and indenol(l,2,3-cd)pyrene (Larsson, 1986).
polyaromatic hydrocarbons (Fig. 3). Cereals appear to be the principal contributor (about 34%0), followed by vegetables (about 18%) and oils and fats (about 16%). Smoked fish contributed only a few percent. The intake of cereals would, on an average, mean 330 ~g/person per year (Larsson, 1986). It is obvious when looking at Fig. 2 that already the consumption of 0.5-1 kg of clams/yr f r o m a polluted area will contribute considerably more. There seems to be very little data on concentrations in marine organisms for most of the chemicals classified by I A R C as 'associated' or 'highly probably associated' with cancer in humans, or for which there is considered to be sufficient evidence o f carcinogenicity in experimental animals. For certain key chemicals (e.g., dioxins, toxaphene, PCBs, D D T derivatives, other organo-halogens, benzo(a)pyrene, other hydrocarbons, arsenic, and certain other metals) data from different parts of the world are available. These data show that there can be a considerable accumulation in fish, shellfish and marine mammals. These data are seldom published in the open literature and are, therefore, not readily accessible. It is natural that the highest concentrations of carcinogens have usually been found close to point sources of pollution in harbors, estuaries and rivers but, as pointed out by the working group, elevated levels of carcinogens have also been reported in some large confined waters (e.g., the Baltic, Mediterranean, North American Great Lakes). In these waters the reported levels in marine organisms are a b o u t 10 times higher than those in the open seas of the North Atlantic or the North Pacific.
390
RISK ASSESSMENT
Risk assessments based on concentrations of carcinogenic substances in marine organisms used as food have, with few exceptions, not been carried out. However, in the preparation of an Environmental Health Criteria Document (WHO, 1981) risk assessment procedures were used for arsenic in water. If the bioavailability of inorganic arsenic in food is the same as that for arsenic in water, the available data indicate that an increased risk of squamous carcinomas of the skin can be associated with high consumption of fish which contains high levels of inorganic arsenic. Risk assessments have been made also for PCBs in fish (Cordle et al., 1982). This assessment was based on animal experimental data, which makes the findings more uncertain. The estimation indicates that, based on a nonthreshold model, an increased risk of cancer can be caused by the consumption of fish containing high levels of PCBs. During the evaluation within Working Group 13 it was found that there were several studies where liver tumors a n d / o r skin papillomas had been produced experimentally in fish. Furthermore, a number of field studies in several areas of the world report such tumors. It was recognized, however, that there are great difficulties in carrying out systematic tumor studies of fish using epidemiological methods. In order to utilize existing fish survey resources effectively, an international cooperative multidisciplinary p r o g r a m is needed, involving fish ecologists, fish pathologists, h u m a n epidemiologists, toxicologists and analytical chemists ( G E S A M P , 1986c). There is a lack of epidemiological data with focus directly on the risks for humans. Dietary factors are most probably a m a j o r causative element in the etiology of h u m a n cancers (see, e.g., Doll and Peto, 1981; Swedish Cancer Committee, 1984). The role of industrial chemical contamination of food has not been determined. In spite of the existence of a large number of studies on the association between diet and cancer, consumption of seafood in the etiology of h u m a n cancer has only rarely been considered. RECOMMENDATIONS
Based on the reviews and evaluations carried out so far a recommendation has been submitted to G E S A M P to the effect that 'the organizations concerned consider, as a matter of urgency, the mobilization of the necessary support for the further development and acceleration of work on the Impact of Carcinogenic Substances on Marine Organisms and Implications concerning Public Health'. At the last review meeting (GESAMP, 1986c) the above recommendation was formulated as a need to carry out comprehensive reviews and evaluations of all aspects of the hazards of carcinogens in the marine environment. Such studies should cover fish, invertebrates, marine birds, m a m m a l s as well as risks for humans. A detailed
391 review o f h u m a n fish c o n s u m p t i o n p a t t e r n s should be i n c l u d e d as well as the p a t h w a y s for carcinogens via fish meals. It was recognized that the work p r o p o s e d will be time c o n s u m i n g , will need to use a m u l t i d i s c i p l i n a r y a p p r o a c h a n d involve specialists in several fields. F u l l - t i m e s u p p o r t staff a n d other resources will be needed for a m i n i m u m period of a b o u t 3 yr. It was p o i n t e d o u t that such a review m u s t f o r m the scientific basis for a n y evaluat i o n s o f the ' s a f e t y ' or p e r c e p t i o n of ' s a f e t y ' o f c o n s u m p t i o n o f fish f r o m different parts o f the world a n d will, therefore, be o f key i m p o r t a n c e for the c o m m e r c i a l a n d sport fisheries. T h e p r o b l e m o f how a n d w h e n tO proceed is, to a great extent, o f a financial n a t u r e . A n y t h o r o u g h e v a l u a t i o n , even w i t h o u t i n v e s t m e n t s for new research, w o u l d need s u b s t a n t i a l e c o n o m i c s u p p o r t . As m e n t i o n e d in the i n t r o d u c t i o n G E S A M P has recognized the potential severity o f the p r o b l e m as well as the diversity a n d complexity o f the subject, i.e., a dual focus o n the occurrence o f t u m o r s in fish as well as o n h u m a n carcinogenicity related to seafood c o n s u m p t i o n . A considerable interest has been expressed also by the L o n d o n D u m p i n g C o n v e n t i o n a n d the Oslo C o m m i s s i o n . F o r the time being n o special f u n d s have been e a r m a r k e d for further work in the field. It is expected that the C h a i r m a n o f the W o r k i n g G r o u p at the next meeting o f G E S A M P , M a r c h 1987, will report o n possibilities o f o b t a i n i n g external s u p p o r t for further work.
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392 Friberg, L., T. Kjellstr6m and G.F. Nordberg, 1986a. Cadmium. In: Handbook on the toxicology of metals, Vol. II, edited by L. Friberg, G.F. Nordberg and V.B. Vouk, Elsevier, Amsterdam, pp. 130-184. Friberg, L., C.-G. Elinder, T. Kjellstr6m and G.F. Nordberg, eds., 1986b. Cadmium and health: a toxicological and epidemiological appraisal, Vols. I, II, CRC Press, Boca Raton, FL, 209, 307 pp. GESAMP, 1985a. Review of potentially harmful substances - cadmium, lead and tin. WHO Rep. Stud. 22, Geneva. GESAMP, 1985b. The impact of carcinogenic substances on marine organisms and implications concerning public health, GESAMP XV/2/4. WHO Intern. Rep, Geneva. GESAMP, 1986a. Review of potentially harmful substances - arsenic, mercury and selenium, WHO Rep. Stud. 28, Geneva. GESAMP, 1986b. Impact of carcinogenic substances on marine organisms and implications concerning public health, GESAMP XVI/2/3. WHO Intern. Rep, Geneva. GESAMP, 1986c. Occurrence of potential carcinogens and tumours in marine organisms, GESAMP XVI/2/4. WHO Intern. Rep, Geneva. H6gberg, J. and J. Alexander, 1986. Selenium. In: Handbook on the toxicology of metals, Vol. If, edited by L. Friberg, G.F. Nordberg and V.B. Vouk, Elsevier, Amsterdam, pp. 482-520. Ishinishi, N., K. Tsuchiya, M. Vahter and B.A. Fowler, 1986. Arsenic. In: Handbook on the toxicology of metals, Vol. II, edited by L. Friberg, G.F. Nordberg and V.B. Vouk, Elsevier, Amsterdam, pp. 43-83. Larsson, B., 1986. Polycyclic aromatic hydrocarbons in Swedish foods. Aspects on analysis, occurrence and intake. Doctoral thesis, Swedish University of Agricultural Sciences, Uppsala. Magos, L., 1986. Tin. In: Handbook on the toxicology of metals, Vol. II, edited by L. Friberg, G.F. Nordberg and V.B. Vouk, Elsevier, Amsterdam, pp. 568-593. Malins, D.C., B.B. McCain, D.W. Brown, S.-L. Chan, M.S. Myers, J.T. Landahl, P.G. Prohaska, A.J. Friedman, L.D. Rhodes, D.G. Burrows, W.D. Gronlund and H.O. Hodgins, 1984. Chemical pollutants in sediments and diseases of bottom-dwelling fish in Puget Sound, Washington. Environ. Sci. Technol. 18, 705-713. Mattson, B., 1977. Completeness of registration in the Swedish Cancer Registry. Stat. Rep. HS 1977, 12. Nat. Swed. Cent. Bur. Stat., Stockholm. Rothman, J.J. and J.D. Boice, 1979. Epidemiologic analysis with a programmable calculator. DHEW Publ. (NIH) 79-1649, U.S. Government Printing Office, Washington, DC. Swedish Cancer Committee, 1984. Cancer - causes - prevention, etc. SOU 1984, 67. Minis. Health Soc. Aff., Stockholm. Swedish Cancer Environment Register, 1980. National Board of Health and Welfare Committee for the Cancer Environment Register in collaboration with the National Swedish Central Bureau of Statistics and the Swedish Work Environment Fund, Stockholm. UNEP, 1980. Report of the UNEP/FAO/WHO meeting of experts on environmental quality criteria for mercury in Mediterranean seafood. Rep. UNEP/MED-HG/14, UN Environ. Program., Nairobi, 19 PP. Varanasi, U. and D.J. Gmur, 1981. Hydrocarbons and metabolites in English sole (Parophrys vetulus) exposed simultaneously to (3H)benzo(a)-pyrene and (14C)naphthalene in oil-contaminated sediment. Aquat. Toxicol. 1, 49. Varanasi, U., D.J. Gmur and P.A. Treseler, 1979. Influence of time and mode of exposure on biotransformation of naphthalene by juvenile starry flounder (Platchthys stellatus) and rock sole (Lepidopsetta bilineata). Arch. Environ. Contam. Toxicol. 8, 673-692. WHO, 1976. Environmental health criteria 1. Mercury. WHO, Geneva, 132 pp. WHO, 1980a. Environmental health criteria 15. Tin and organotin compounds. WHO, Geneva, 109 pp. WHO, 1980b. Consultation to re-examine the WHO environmental health criteria for mercury. EHE/EHC/80.22, WHO Geneva Intern. Rep., 18 pp.
393 WHO, 1981. Environmental health criteria 18. Arsenic. WHO, Geneva, 174 pp. WHO, 1985. Guidelines for the study of dietary intakes of chemical contaminants, GEMS. WHO Offset Publ. 87, Geneva. WHO, 1986. Environmental health criteria. Selenium. WHO, Geneva, in press. Wiklund, K., J. Einhorn and G. Wennerstrfm, 1981. Swedish cancer environment register available for research. Scand. J. Work Environ. Health 7, 64-67.