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Keywords:

  • Toxicological risk;
  • Toxaphene;
  • Fish;
  • Human;
  • European fish consumption

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. ESTIMATION OF A TOLERABLE DAILY INTAKE (TDI) FOR TOXAPHENE FOR TUMOR PROMOTION POTENCY
  5. MAXIMUM RESIDUE LEVEL AND TOLERABLE DAILY INTAKES
  6. AVERAGE DAILY AND YEARLY INTAKE OF TOXAPHENE
  7. RISK OF TOXAPHENE INTAKE FROM FISHERY PRODUCTS
  8. CONCLUSIONS
  9. Acknowledgements
  10. REFERENCES

A revised risk assessment for toxaphene was developed, based on the assumption that fish consumers are only exposed to toxaphene residues that differ substantially from technical toxaphene due to environmental degradation and metabolism. In vitro studies confirmed that both technical toxaphene and degraded toxaphene inhibit gap junctional intercellular communication that correlates with the mechanistic potential to cause tumor promotion. In vivo rat studies established the NOAEL for degraded and technical toxaphene at the highest dose tested in the bioassay. Toxaphene residue intakes from European fishery products were estimated and compared to the provisional tolerable daily intakes (TDIs) from various regulatory agencies including Canada, the United States, and Germany. The estimated intake was also compared to a new calculated provisional MATT pTDI. The MATT pTDI is based on new toxicological information (in vivo rat studies) developed on a model for environmental toxaphene residues rather than technical toxaphene. A MATT pTDI (1.08 mg total toxaphene for a person of 60 kg) for tumor promotion potency was adopted for use in Europe and is referred to here as the MATT pTDI. These new data result in a better estimate of safety and a higher TDI than previously used. Based on realistic fish consumption data and recent baseline concentration data of toxaphene in European fishery products, the toxaphene intake for the consumers of Germany, Ireland, Norway, and the Netherlands was estimated. For an average adult fish consumer, the average daily intake of toxaphene was estimated to be 1.2, 0.4, 0.5, and 0.2 µg for the consumers of Norway, Germany, Ireland, and the Netherlands, respectively. The toxaphene intake of these average fish consumers was far below the MATT pTDI of 1.08 mg/60 kg bw. In conclusion, based on the most relevant toxicological studies and the most realistic estimates of fish consumption and recent concentrations of toxaphene in European fishery products, adverse health effects are unlikely for the average European consumer of fishery products. In no case is the MATT pTDI exceeded. Integr Environ Assess Manag 2012; 8: 523–529. © SETAC


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. ESTIMATION OF A TOLERABLE DAILY INTAKE (TDI) FOR TOXAPHENE FOR TUMOR PROMOTION POTENCY
  5. MAXIMUM RESIDUE LEVEL AND TOLERABLE DAILY INTAKES
  6. AVERAGE DAILY AND YEARLY INTAKE OF TOXAPHENE
  7. RISK OF TOXAPHENE INTAKE FROM FISHERY PRODUCTS
  8. CONCLUSIONS
  9. Acknowledgements
  10. REFERENCES

Given the concern for the worldwide environmental effect of toxaphene, surprisingly little is known about the toxicology of this group of compounds (de Geus et al. 1999; Swackhamer et al. 1993; Arnold et al. 2001; Bryce et al. 2001). It is essential that the quality of the aquatic environment and consumers of marine foodstuffs be protected. However, a large number of uncertainties exist in the data or data are even absent with regard to the analysis, baseline levels, carcinogenicity, toxicological risk, tolerance levels, and fate of toxaphene in the environment (de Geus et al. 1999). Consequently, a proper risk assessment of toxaphene for the consumer of marine foodstuffs could not be conducted previously. In the European project, Investigation into the Monitoring, Analysis and Toxicity of Toxaphene in Marine Foodstuffs (MATT), new information on the monitoring, analysis, toxicology, and risks of toxaphene was obtained (McHugh et al. 2004; Besselink et al. 2008).

Tolerance levels are based on the toxicology of technical toxaphene mixture, but the number and pattern of congeners in environmental samples are substantially different, as a result of environmental and metabolic modification, from the technical toxaphene mixture. Human exposure is mainly through consumption of toxaphene-contaminated fish (Berti et al. 1998). The composition of toxaphene mixtures changes from the original technical toxaphene mixtures through environmental transformation and internal metabolism in the fish. Human exposure, therefore, is to a weathered mixture of technical toxaphene. However, the toxic and carcinogenic properties of toxaphene residues in fish were unknown. No carcinogenicity studies at all on weathered toxaphene have been reported in the literature. The study of Buranatrevedh (2004) showed that toxaphene might have a carcinogenic risk for humans based on a 4-step risk assessment, however, this risk assessment used data from toxicity studies using technical toxaphene. Besselink et al. (2008) developed new toxicology data using a more realistic exposure of test animals to degraded toxaphene. The toxicology test mimics the weathered toxaphene pattern found in fish and should provide a more realistic model of the human exposure situation. The procedure exposed fish (cod) to technical toxaphene mixture. Toxaphene residues were then extracted from the liver of the exposed fish, which showed the weathered toxaphene pattern. The extracted toxaphene residues were used in in vitro experiments to demonstrate the plausibility that technical toxaphene and degraded toxaphene inhibited gap junctional intercellular communication as a correlate to tumor promotion. They also ran a critical in vivo exposure study with rats to determine the tumor promotion potency of technical and weathered toxaphene residues. In addition, UV-irradiated toxaphene was tested in in vivo and in vitro studies. The no observed adverse effect levels (NOAELs) in the in vivo studies are used to set a new tolerable daily intake (referred to as the provisional MATT TDI) for toxaphene for the tumor promotion potency. The MATT TDI is compared with other proposed TDIs.

The objectives of the present study were to estimate a TDI for weathered toxaphene for tumor promotion based on the new toxicological data, to estimate the daily intake of toxaphene residues from European fishery products for the consumers of Germany, Ireland, Norway, and the Netherlands, and to provide information on the toxicological risks to consumers of toxaphene residues from fishery products from European waters.

The daily intake of toxaphene was estimated from 1) the baseline levels of toxaphene in fish and shellfish (McHugh et al. 2004), and 2) the daily consumption of fishery products for the consumers of Germany, Ireland, Norway, and the Netherlands. The daily consumer intake of toxaphene was compared with TDIs set by Canada, the United States, and Germany, and the provisional MATT TDI calculated in our study based on a new tumor promotion potency study (Besselink et al. 2008).

ESTIMATION OF A TOLERABLE DAILY INTAKE (TDI) FOR TOXAPHENE FOR TUMOR PROMOTION POTENCY

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. ESTIMATION OF A TOLERABLE DAILY INTAKE (TDI) FOR TOXAPHENE FOR TUMOR PROMOTION POTENCY
  5. MAXIMUM RESIDUE LEVEL AND TOLERABLE DAILY INTAKES
  6. AVERAGE DAILY AND YEARLY INTAKE OF TOXAPHENE
  7. RISK OF TOXAPHENE INTAKE FROM FISHERY PRODUCTS
  8. CONCLUSIONS
  9. Acknowledgements
  10. REFERENCES

To derive a TDI for humans, toxicity data from mammals are used in combination with a safety factor. The TDI is defined as the daily intake of a contaminant, in this case toxaphene, which should not result in adverse health effects. Normally, one applies a safety factor of 100, 10 for the extrapolation of an effect level from animal experiments to humans and 10 to account for variability among humans. In the 1950s, the Joint Expert Committee on Food Additives (JECFA) set a safety factor of 100-fold to protect humans based on a NOAEL in animals (factor 10 for species differences and a factor 10 to allow for interindividual differences). The Codex (2000) discussion article advised applying a safety factor of 1000 for toxaphene. The extra safety factor of 10 for toxaphene was supported by the observed variation in toxaphene patterns between the technical toxaphene mixture and the patterns found in the environment, and because most toxicity studies have been performed with technical toxaphene. Toxicological studies were carried out by Besselink et al. (2008) on 3 toxaphene mixtures including technical toxaphene (TT), UV-irradiated toxaphene (UVT), and toxaphene residues extracted from cod liver (CLE). As a result of the additional information from these experiments, the extra safety factor of 10 is considered no longer necessary.

With respect to the calculation of a MATT pTDI from the in vivo toxicity studies of the Besselink et al. study (2008), the cod liver experiment is preferred for the calculation of the MATT pTDI because this extract mimics the toxaphene pattern found in fish and therefore provides a more realistic human exposure situation. We note that the cod liver extract (CLE) showed a weathered toxaphene pattern, however: the residue samples were less altered than expected based on residues typically found in marine fish. The most likely reason for that observation is that the major changes in the technical toxaphene pattern take place before the uptake by fish, whereas toxaphene is in the environment where it is exposed to UV light, evaporation, etc. However, the chromatograms show that in fish some changes in technical toxaphene have also taken place (Besselink et al. 2008). The present data indicate that the highest exposure concentration for the cod liver extract should serve as an NOAEL for tumor promotion in female Sprague–Dawley rats (Besselink et al. 2008). The highest dose used in the cod liver extract experiment was 12.5 mg technical toxaphene equivalents/kg bw/week, which is 1.8 mg/kg bw/day (Table 1). This level is the NOAEL. The MATT established a safety factor of 100 considering the uncertainties of intra- and interspecies differences. Although an extra factor of 10 was proposed by the Nordic Council, the MATT group determined that it was not required, because the prior uncertainty was addressed by the Besselink et al. (2008) studies on the 2 forms of degraded toxaphene (UVT and CLE). Applying a safety factor of 100 to the NOAEL, the MATT pTDI for humans for toxaphene for tumor promotion potency is 0.018 mg/kg bw/d. This results in an MATT pTDI of 1.08 mg for total toxaphene per day for a person with a body weight of 60 kg (0.018 mg/kg bw/d × 60 kg bw = 1.08 mg/d) (Table 1).

MAXIMUM RESIDUE LEVEL AND TOLERABLE DAILY INTAKES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. ESTIMATION OF A TOLERABLE DAILY INTAKE (TDI) FOR TOXAPHENE FOR TUMOR PROMOTION POTENCY
  5. MAXIMUM RESIDUE LEVEL AND TOLERABLE DAILY INTAKES
  6. AVERAGE DAILY AND YEARLY INTAKE OF TOXAPHENE
  7. RISK OF TOXAPHENE INTAKE FROM FISHERY PRODUCTS
  8. CONCLUSIONS
  9. Acknowledgements
  10. REFERENCES

Several tolerance levels and maximum residue levels in food for toxaphene have been proposed based on total toxaphene or on the sum of 3 persistent indicator congeners (Simon and Manning 2006). Either approach can be used to develop a valid and safe level for toxaphene in the food. Germany use a maximum residue level (MRL) of 0.1 mg/kg wet weight (w/w) on the basis of the sum of the 3 indicator congeners (CHBs 26, 50, and 62) for fish and fish products. The German MRLs for all other food of animal origin were set at 0.1 mg/kg w/w on the basis of total toxaphene (Anonymous 1997; Table 2). Canada also uses total toxaphene residues to set an allowable daily intake (ADI) of 0.2 µg/kg bw/d, which is equivalent to a tolerable daily intake (TDI) of 0.012 mg for a person of 60 kg (Table 2).

The US Environmental Protection Agency (USEPA) set 2 health benchmarks for toxaphene; a chronic toxicity reference dose of 2.5 × 10−4 mg/kg/d (USEPA 1997) and, for carcinogenicity, the upper bound (95% confidence limit) cancer slope factor (CSF) that is 1.1 (mg/kg/d)−1 with a maximum acceptable upper bound cancer risk level of 10−5 (1 in 100 000) over a 70-year lifetime (USEPA 1999). Based on an acceptable risk of 10−5, the maximum average daily dose can be estimated to approximate a reference dose for carcinogenicity. The chronic dose for an average body weight of a person of 60 kg for toxaphene is 0.015 mg. On a body weight basis, the dose is 0.015/60 or 0.00025 mg/kg/d (Table 2). For carcinogenicity, the upper bound risk of toxaphene in fisheries products can be estimated by multiplying CSF with the concentration of toxaphene in fisheries products (Cf), the average yearly fish consumption (FCyr), and the exposure duration (30 years). This average lifetime intake should be divided by body weight (BW) and an average lifetime of 70 years (see Equation 1). The risk is expressed in terms of an upper bound incidence, for example a certain exposure would result in an estimate of risk that has a 95% probability of being no greater than x (e.g., x is 1 in a million or 1 in 100 000) and could be as low as zero.

  • equation image

CSF, cancer slope factor, 1.1 per mg/kg/day−1; Cf, toxaphene concentration in fish (mg/kg), data from McHugh et al. (2004); FCyr, average yearly fish consumption, kg/year; ED, exposure duration, 30 years; BW, body weight, kg; L, lifetime, 25 550 days = 70 years.

The cancer slope factor approach was reviewed by Goodman et al. (2000). They proposed the risk assessment be revised under the 1986 USEPA cancer risk assessment guidelines. Goodman et al. (2000) proposed a lower potency factor. The Simon and Manning (2006) proposal would abandon the slope factor for a margin of safety calculation.

Table 1. Overview of effect levels and parameters used to derive a TDI for toxaphenea
 Level
  • TDI = tolerable daily intake.

  • a

    No observed adverse effect dose was taken from Besselink et al. (2008).

No observed effect level dose of cod liver extract for rat12.5 mg/kg bw/week
No observed effect level dose of cod liver extract for rat adjusted for daily intake1.8 mg/kg bw/d
Safety factor for extrapolation from rat to human100
Tolerable daily intake per kg body weight for humans0.018 mg/kg bw/d
Proposed TDI for a person of 60 kg1.08 mg/d

The most recent proposal from Simon and Manning (2006) creates a reference dose (essentially the same as a TDI) using 3 persistent congeners as the measure of toxaphene in the environment. The 3 persistent congeners (congeners p-26, p-50, and p-62) represent the entire group of toxaphene congeners, so the values are lower than total toxaphene numbers. They propose the reference dose at 2E-05 mg/kg/day of the 3 persistent congeners based on the same toxicology data that are relied on in this risk assessment. Simon and Manning used the NOAEL from the in vivo rat study on cod liver extract toxaphene (Simon and Manning 2006; Besselink et al. 2008).

Table 2. Overview of maximum TDI values of toxaphene for a person of 60 kg and MRL in fish and fish products
 Value
  • MRL = maximum tolerable levels; TDI = tolerable daily intake.

  • a

    TDI calculated from the proposed ADI based on a person of 60 kg.

  • b

    Based on a cancer slope factor of 1.1 (mg/kg/d)−1.

  • c

    The acceptable level was converted to total toxaphene assuming a toxaphene mixture contains 10% Σ3PC (p26 + p50 + p62).

TDI
 Canada, pTDIa0.012 mg/d
 USEPA, chronic toxicitya0.015 mg/d
 For acceptable upper bound risk of 1 in 100 000b0.00025 mg/d

 Simon and Manning (2006)

proposed RfD
0.012 mg/dc
 This study, tumor promotion potency1.08 mg/d
MRL
 Germany0.1 mg/kg w/wc

AVERAGE DAILY AND YEARLY INTAKE OF TOXAPHENE

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. ESTIMATION OF A TOLERABLE DAILY INTAKE (TDI) FOR TOXAPHENE FOR TUMOR PROMOTION POTENCY
  5. MAXIMUM RESIDUE LEVEL AND TOLERABLE DAILY INTAKES
  6. AVERAGE DAILY AND YEARLY INTAKE OF TOXAPHENE
  7. RISK OF TOXAPHENE INTAKE FROM FISHERY PRODUCTS
  8. CONCLUSIONS
  9. Acknowledgements
  10. REFERENCES

To estimate the average daily intake of toxaphene from fishery products for the consumers of Germany, Ireland, Norway, and the Netherlands, information on the consumption of fishery products is needed. The Statistical Office of the European Communities in Luxembourg (Eurostat) provides information on the fish production of European countries (see Table 3) (Eurostat 2001). However, the Eurostat data accounts for the fish production without exports and some other factors. The data are based on the whole fish weight and not just the edible portion of the fish, and therefore the fish consumption will be overestimated. The FAO database also includes information on the world-fish production (Table 3). Detailed fish consumption data in the Netherlands have shown, however, that a large difference exists in the amount of fish production and the amount of fish consumption (edible part of the fish) (Temminghoff 1999). For 1998, the average fish consumption in the Netherlands was 9.4 g/d, which is 3.4 kg/y and >4-fold lower than the amount of fish production set by Eurostat or FAO. The Irish Sea Fisheries Board (BIM) has statistics on average fish consumption in Ireland, and also these data (8.8 kg of fish and fish products per person) show that the consumption is lower than that based on Eurostat and FAO data. For Germany fish consumption data from the Deutschen Gessellschaft für Ernährung (DGE) showed an average of 14.9 kg/y for whole fish. We assume that the real consumption of fish is 50% of the whole fish, 7.5 kg/y. For Norway the Statens Næringsmiddeltilsyn (SNT) Institute provided a realistic fish consumption of 21.9 kg/y. For both Germany and Norway, the realistic fish consumption data are lower than the Eurostat and the FAO data. Therefore, the most realistic fish consumption data were used for the calculations of the intake of toxaphene from fishery products.

Table 3. Consumption of fishery products (kg/y) per person for Germany, Ireland, Norway, and The Netherlands from Eurostat for 1998 and FAO for 1997.
 Realistic consumption (kg/person/y)Eurostat (kg/person/y)FAO (kg/person/y)
  • a

    Calculated on the basis of 50% consumption of whole fish (14.9 kg/y).

Germany7.5a1215.6
Ireland8.81820.6
Norway21.94669.1
The Netherlands3.41214.6

For the intake estimations from fishery products, recent baseline concentration data for toxaphene in fishery products from the North-east Atlantic (North Sea, German Bight/Skagerak, Baltic Sea, Irish Sea, Irish west coast, Norwegian coast, and Barents Sea) were used (McHugh et al. 2004). Liver samples were removed from the data set, and only fillet or shellfish samples were included. In the study of McHugh et al. (2004) concentrations of toxaphene were determined in 221 fillet samples of fishery products from the North-East Atlantic, as well in farmed fish samples. In all samples the 3 indicator congeners (CHB 26, 50, and 62) as well as total toxaphene were determined in 55 samples. Based on the ratio of the sum of the 3 indicator congeners and total toxaphene, the total toxaphene concentration in the other samples was estimated. The ratios for marine fish, eel and mussel were 12%, 42%, and 24%, respectively. This data set was used to estimate the average daily intake of total toxaphene and the intake of the sum of the 3 indicator congeners.

The daily intake of toxaphene (Iintake) was calculated (Table 4) by multiplying the toxaphene concentration of each individual sample on a wet weight basis (Cfish) with the average daily consumption of fishery products (FCd):

  • equation image
Table 4. Estimated average daily intake (µg) of toxaphene from fishery products for the consumers of Germany, Ireland, Norway, and the Netherlands
CountryAverage daily fish consumption (g/d)a (FCd)Estimated average daily intake (µg) of toxaphene by fishery products (Iavg)Estimated range of daily intake (µg) of toxaphene by fishery products for low and high contaminated fish
  • a

    Realistic fish consumption.

Germany20.40.40.001–5
Ireland24.10.50.002–6
Norway60.01.20.004–14
The Netherlands9.40.20.001–2

To estimate the lifetime average daily intake of toxaphene (Iavg) the following assumptions were made:

  • All people had access to all fishery products.

  • All fishery products were eaten in equal amounts.

  • The baseline survey samples are a good representation of commercial fishery products.

The average daily intake (Iavg) was estimated as the mean of the intake of all individual samples (Iintake):

  • equation image

in which n is the total number of samples. In reality preferences for the consumption of some fish species exists in countries, e.g., a Scandinavian penchant for herring. Yet, detailed information on the fish consumption (species frequency and amounts) was not available for the countries and, therefore, was not used in this study.

The highest estimated average daily intake of total toxaphene (1.2 µg) was found for Norway, and 0.4, 0.5, and 0.2 µg for Germany, Ireland, and the Netherlands, respectively. However, people in Iceland eat on average even more fish than those in Norway, and an intake of 2.6 µg/d is estimated. An estimated intake of toxaphene from fish for people from Greenland is estimated to vary from 0.03 to 6.7 µg/d (Johansen et al. 2004). The estimated daily intakes of total toxaphene are in agreement with the daily intakes reported by Alder et al. (1997) for Germany, 2.8–5.6 ng/kg bw, which is 0.2–0.3 µg for a person of 60 kg/d. A similar daily intake has been reported by Brüschweiler et al. (2004), based on fish, meat, milk, and plant samples, of 25 ng total toxaphene/kg bw, which is equivalent to 1.5 µg for a person of 60 kg. The range of estimated daily intakes of toxaphene from low contaminated fish to higher contaminated fish varied between 0.001 and 14 µg (Table 4).

RISK OF TOXAPHENE INTAKE FROM FISHERY PRODUCTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. ESTIMATION OF A TOLERABLE DAILY INTAKE (TDI) FOR TOXAPHENE FOR TUMOR PROMOTION POTENCY
  5. MAXIMUM RESIDUE LEVEL AND TOLERABLE DAILY INTAKES
  6. AVERAGE DAILY AND YEARLY INTAKE OF TOXAPHENE
  7. RISK OF TOXAPHENE INTAKE FROM FISHERY PRODUCTS
  8. CONCLUSIONS
  9. Acknowledgements
  10. REFERENCES

A comparison of TDIs and the estimated average daily intake of toxaphene from all baseline samples of McHugh et al. (2004) is shown in Figure 1. This figure shows that only 1 baseline sample (Greenland halibut) exceeded the Canadian TDI for the Norwegian consumer. On an average basis the TDIs are not exceeded. The proposed MATT TDI for tumor promotion (1.08 mg total toxaphene) was not exceeded by any of the individual fishery samples. The risk of cancer based on the cancer slope factor and a lifetime intake of toxaphene by fishery products is shown in Figure 2. The maximum acceptable cancer risk of 1E-05 set by the USEPA (USEPA 1999) is marked. Approximately 1.5%, 6%, and 8% of the baseline samples exceeded the maximum cancer risk of 1E-5 for an average Dutch, German, and Irish fish consumer, respectively. For an average Norwegian fish consumer approximately 24% of the samples exceeded the maximum risk level, due to a higher consumption of fish than the consumers of the above 3 countries.

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Figure 1. Frequency distributions of estimated intake of total toxaphene (µg) in 221 fish and shellfish samples from the study of McHugh et al. (2004) and realistic average fish consumption data of Germany, Ireland, Norway, and the Netherlands. The TDI thresholds for Canada (12 µg) and the USEPA for chronic toxicity (15 µg) are shown.

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Figure 2. Frequency distributions of cancer risk estimated from the lifetime intake of total toxaphene from fish and shellfish samples (n = 221) from the study of McHugh et al. (2004) and realistic average fish consumption data of Germany (A), Ireland (B), Norway (C), and the Netherlands (D), and high fish consumption for the Norwegian consumer (E). The number of samples per frequency class is shown at the top of the bars. The USEPA cancer slope factor of 1.1 per mg/kg-d (USEPA 1999) with a maximum acceptable risk level of 1E-05 was used.

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These conclusions are based on an average consumption of fishery products and an adult person of 60 kg. It is known that specific groups of people, for instance fishermen, eat more fish than average. For high fish consumers of Norway (184 g fish/d, 67 kg/y) the estimated daily intake was 3.7 µg instead of 1.2 µg for an average Norwegian fish consumer (60 g fish/d). For the high Norwegian fish consumers approximately 8% of the total number of fish samples exceeds the Canadian TDI, and 5% of the samples are above the USEPA TDI level for chronic toxicity (Figure 3). The samples that exceed the TDI are, in general, fatty fish; 4 herring, 5 mackerel, 2 Greenland Halibut, 4 farmed Atlantic Salmon, and 1 eel. A large number of these samples came from the Barents Sea, which has been shown to contain elevated levels of toxaphene (McHugh et al. 2004). The maximum acceptable risk level of 1E-5 for cancer was exceeded by 24% of the samples for an average Norwegian fish consumer and by >50% of the baseline samples for high fish consumers of Norway.

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Figure 3. Frequency distributions of estimated intake of total toxaphene (µg) in 221 fish and shellfish samples from the study of McHugh et al. (2004) and average and high fish consumption for the Norwegian consumer. The TDI thresholds for Canada (12 µg) and the USEPA for chronic toxicity (15 µg) are shown.

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In addition to the differences in fish consumption between groups of people, regional differences within a country also exist. For instance, in Germany a large variation in fish consumption is present between the northern and southern regions. Figure 4 shows the estimated average daily intake of toxaphene for 3 German regions.

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Figure 4. Frequency distributions of estimated daily intake of total toxaphene (µg) based on toxaphene levels in 221 fish and shellfish samples from the study of McHugh et al. (2004) and average consumption of fishery products from 3 regions in Germany. Average fish consumption for Schleswig-Holstein, Hamburg and the northern part of Lower Saxony are 41.1 g/person/d, for Nordrhein-Westfalen 15.1 g/person/d, and for Bavaria and Baden-Württeberg 6.2 g/person/d. TDI thresholds for Canada (12 µg) and the USEPA for chronic toxicity (15 µg) are shown.

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With regard to the maximum residue level (MRL) set by Germany, all baseline samples were below the threshold level of 0.1 mg/kg w/w for the sum of the 3 indicator congeners in fish and fish products (Figure 5). It is important to note that the MRL is based on the toxaphene concentration in the fish product and is not related to the amount of fish consumption.

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Figure 5. Concentration of the sum of the 3 indicator toxaphene congeners in fishery products from McHugh et al. (2004) compared to the maximum residue limit (MRL) set in Germany of 0.1 mg/kg w/w.

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CONCLUSIONS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. ESTIMATION OF A TOLERABLE DAILY INTAKE (TDI) FOR TOXAPHENE FOR TUMOR PROMOTION POTENCY
  5. MAXIMUM RESIDUE LEVEL AND TOLERABLE DAILY INTAKES
  6. AVERAGE DAILY AND YEARLY INTAKE OF TOXAPHENE
  7. RISK OF TOXAPHENE INTAKE FROM FISHERY PRODUCTS
  8. CONCLUSIONS
  9. Acknowledgements
  10. REFERENCES

In the past, toxaphene risks were based on toxicology data on technical toxaphene. The adverse effect driving the risk assessment was tumor promotion. In vitro studies have confirmed that TT, CLE, and UVT all show a biologically plausible ability to inhibit gap junctional intercellular communication. In vivo studies have established the NOAEL for each of these, and the CLE-generated NOAEL is proposed for use in the risk assessment. These new risk data based on toxaphene residues in fish and established in the MATT project show that the risks associated with fish consumption in Europe regarding toxaphene concentrations are negligible, and in the worst case scenario are limited to high fish consumers in Norway and possibly Iceland. However, when using the USEPA cancer slope factor approach, a substantially higher risk is predicted. The cancer slope factor approach may, be too conservative however, and the MATT data on tumor promotion do not support this approach. The new toxicological data from the MATT project show that Norwegian fish consumers are not exposed to serious risks due to toxaphene.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. ESTIMATION OF A TOLERABLE DAILY INTAKE (TDI) FOR TOXAPHENE FOR TUMOR PROMOTION POTENCY
  5. MAXIMUM RESIDUE LEVEL AND TOLERABLE DAILY INTAKES
  6. AVERAGE DAILY AND YEARLY INTAKE OF TOXAPHENE
  7. RISK OF TOXAPHENE INTAKE FROM FISHERY PRODUCTS
  8. CONCLUSIONS
  9. Acknowledgements
  10. REFERENCES
  • Alder L, Beck H, Khandker S, Karl H, Lehman I. 1997. Levels of toxaphene indicator compounds in fish. Chemosphere 34: 13891400.
  • Anonymous. Third amendment of the German maximum residue limit ordinance of 26 September 1997, BGBI.I p. 2366, Berlin, Germany.
  • Arnold DL, Bryce F, Baccanale C, Hayward S, Tanner JR, MacLellan E, Dearden T, Fernie S. 2001. Toxicological consequences of toxaphene ingestion by cynomolgus (Macaca fascicularis) monkeys. Part 1: Pre-mating phase. Food Chem Toxicol 39: 467476.
  • Berti PR, Receveur O, Chan HM, Kuhnlein HV. 1998. Dietary exposure to chemical contaminants from traditional food among adult Dene/Metis in the Western Northwest Territories, Canada. Environ Res 76: 131142.
  • Besselink H, Nixon E, McHugh B, Rimkus GG, Klungsøyr J, Leonards PEG, de Boer J, Brouwer A. 2008. Evaluation of tumor promoting potency of fish borne toxaphene residues, as compared to technical toxaphene and UV-irradiated toxaphene. Food Chem Toxicol 46: 26292638.
  • Bryce F, Iverson F, Andrews P, Barker M, Cherry W, Mueller R, Pulido O, Hayward S, Fernie S, Arnold DL. 2001. Effects elicited by toxaphene in the cynomolgus monkey (Macaca fascicularis): A pilot study. Food Chem Toxicol 39: 12431251.
  • Brüschweiler BJ, Spriano D, Schlatter J. 2004. Gesundheitliche Risikobewertung der Toxaphen-R¨ckstände in Lebensmitteln. Mitt Lebensm Hyg 95: 162189.
  • Buranatrevedh S. 2004. Cancer risk assessment of toxaphene. Industr Health 42: 321327.
  • Codex. 2000. Codex Alimentarius Meeting of the Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO) on Pesticide Residues; 2000 May 1-8; The Hague, the Netherlands.
  • De Boer J, Wester P. 1993. Determination of toxaphene in human milk from Nicaragua and in fish and marine mammals from the Northeastern Atlantic and the North Sea. Chemosphere 27: 18791890.
  • De Geus HJ, Besselink H, Brouwer A, Klunsøyr J, McHugh B, Nixon E, Rimkus GG, Wester PG, de Boer J. 1999. Environmental occurrence, analysis, and toxicology of toxaphene compounds. Environ Health Perspect 107: 115144.
  • Eurostat. 2001. Available from: http://www.eubusiness.com/fooddrin/980720es.htm.
  • [FAO] Food and Agriculture Organization. 2001. Available from: http://www.fao.org/fishery/countrysector/FI-CP_NL/en.
  • Goodman JI, Brusick DJ, Busey WM, Cohen SM, Lamb JC, Starr TB. 2000. Reevaluation of the cancer potency factor of toxaphene: Recommendations from a peer review panel. Toxicol Sci 55: 316.
  • Johansen P, Muir D, Asmund G, Riget F. 2004. Human exposure to contaminants in the traditional Greenland diet. Sci Total Environ 331: 189206.
  • McHugh B, McGovern E, Nixon E, Klungsøyr J, Rimkus GG, Leonards PEG, de Boer J. 2004. Baseline survey of concentrations of toxaphene congeners in fish from European waters. J Environ Monit 6: 665672.
  • Simon T, Manning R. 2006. Development of a reference dose for the persistent congeners of weathered toxaphene based on in vivo and in vitro effects related to tumor promotion. Reg Toxicol Pharmacol 44: 268281.
  • Swackhamer DL, McConnell LL, Gregor DJ. 1993. Workgroup report on environmental transport and fate. Chemosphere 27: 18351840.
  • Temminghoff M. 1999. Vis, Schaal-en schelpdieren Nederland. Martkontwikkeling 1995- 1998. Presentation 1999 March 3, GfK Nederland en Nederlands Visbureau, The Hague, the Netherlands.
  • [USEPA] US Environmental Protection Agency. 1997. Reference dose tracking report. Office of Pesticide Programs, Health Effects Division. Washington (DC): USEPA.
  • [USEPA] US Environmental Protection Agency. 1999. IRIS (Integrated Risk Information System) for toxaphene. National Center for Environmental Assessment, Office of Research and Development. Washington (DC): USEPA.