Cancer risk to naval divers: response.

We would like to address the epidemiologic implications of Amitai et al.'s comments on the validity of our estimates of exposure, dermal contact and absorption, internal doses, and permeability coefficients that we reported in our article published in the April 2003 issue of EHP(Richter et al. 2003)

We now know that excessive skin contact occurred in the 1950s and 1960s when divers used defective and torn skin suits and applied skin greases [Governmental Commission of Inquiry (GICI) 2003]. Strikingly, all cases of melanoma occurred among those who began diving before 1970, and no melanoma was found in those who began diving after 1970 (Richter et al. 2003). The fact that seven of the eight divers with melanoma belonged to the 1960 cohort accounts for the sharp peak in observed/expected ratio (6.58) for all cancers combined in the 1960-1969 cohort.

Our calculations (Richter et al. 2003) were based on data from the GICI (2003). Both the Kishon Harbor and Haifa Bay were severely polluted, and dilution of effluents did not occur until well past the mouth of the Kishon River. Many samples were taken near apertures of effluent drains, where concentrations would be substantially higher before downstream dilution. Most diving took place at the mouth of the Kishon River, Haifa Bay, and Kishon Harbor, close to and downstream from these apertures.

Furthermore, divers frequently descended to sediment depths. Frequent dredging resulted in recirculation of sediment. Therefore, the data on toxics were probably reasonable indicators of the conditions of exposure.

For determining estimated potential exposure dose intake, we used reported water levels only, not substantially higher sediment levels (Richter et al. 2003). Measures such as biological oxygen demand, total suspended solids, and sediment levels for observed pollutants state the case for severe contamination, even if dose estimates based on concentrated water samples are too high.

Regulatory, agencies have used a permeability constant of 1.0 cm/hr and a bioavailability factor of 1.0 rather than measured or estimated values (Great Lakes Health Effects Division 1993). Correcting for the permeability coefficient and bioavailability factor suggests an overestimate of daily intakes by 1.5-3.0, not 5, as stated by Amitai et al. Even so, we are currently addressing the potential for high rates of intake from high concentrations of toxics in subsurface water and still higher concentrations in surface films of petroleum. Solvents, of course, have permeability constants and bioavailability factors higher than those for metals, and many exceed 1.0 (e.g., ethanol, toluene).

In our paper (Richter et al. 2003), we presented estimates normalized to 24 diving hours, not daily exposure, which was 3-4 hr/day for the first year and 2 hr/day for the remaining 3 years of full-time service (Table 3; Richter et al. 2003). Therefore, an estimate of absorption per workday should be approximately one order of magnitude less than the 24-hr value.

Our calculations based on the classical models of exposure and equations (Richter et al. 2003) probably provide substantial underestimates of exposure hazards under real-life conditions.

Several real-life conditions increased the hazard from exposure. First, wet suits acted as occlusive pressure dressings on the skin. Second, abrasions and open cuts facilitate higher penetration (ATSDR 1999b). Third, the divers used abrasive soaps (intended for cleaning horses) and turpentine-containing thinners to clean thick crusts off their skin. Fourth, the soaps, together with detergents in the Kishon waters, produced additional abrasions and surface injury to the skin. Fifth, the thinners removed the protective fat layer on the skin and served as carriers of contaminants in crusts deposited on the skin.

Current blood cadmium and lead levels do not indicate past absorption and exposure. For both Cd and Pb, skin exposure can pose a risk for absorption when contact continues for prolonged periods (several hours) or at very high levels, and when skin is abraded or injured (i.e., common conditions for the divers) (ATSDR 1999a, 1999b). Short-term studies underestimate these risks.

Measurements of blood levels of two heavy metals [greater than or equal to] 8 years after the last exposure certainly do not serve as indicators of occupational exposures to these agents, and certainly not to many lipophilic toxics in the Kishon River. Neither blood Cd nor Pb levels reflect long-time cumulative body burdens or exposures that terminated years ago. The major portion of the Cd body burden is in the liver, kidney, and other tissues; for Pb, it is in bone. In humans, the half-life of Cd in blood is approximately 75-128 days for the fast component and 7.4-16.0 years for a residual slower component (Jarup et al. 1983). The half-life of Pb in blood is only 28-36 days (ATSDR 1999b). Blood presumably contains Pb that is transferring in and out of other compartments.

Figure 1 presents cumulative risks for all cancers combined in terms of years lapsed from first exposure to diving. Short induction periods follow the onset of exposure, and reversibility reaches unity at 42 years after the first exposure (after full-time exposure is terminated), a strong argument for causation.

[FIGURE 1 OMITTED]

We question the validity of estimating risks for long-term exposures from toxicokinetic models derived from short-term controlled experimental settings. If we have overestimated dermal exposure and absorption, then internal doses far lower than our original estimates were sufficient to produce the increase in risks, and removal of these exposures reversed the increase.

The authors declare they have no conflict of interest. One author, Y. Tamir, a diver with cancer, played a key role in the process of data collection.

Elihu D. Richter

Lee S. Friedman

Hebrew University-Hadassah

Jerusalem, Israel

E-mail: [e-mail]

Yuval Tamir

Israel Defense Forces (Retired)

Tamar Berman

Maya Sadeh

Or Levy

Jerome B. Westin

Tamar Peretz

Hebrew University-Hadassah

Jerusalem, Israel

Irene Lipshitz

Micha Bar-Chana

Ministry of Health

Jerusalem, Israel

REFERENCES

ATSDR. 1999a. Toxicological Profile for Cadmium (Update), Atlanta, GA:Agency for Toxic Substances and Disease Registry.

--. 1999b. Toxicological Profile for Lead (Update). Atlanta, GA:Agency for Toxic Substances and Disease Registry.

Governmental Commission of Inquiry (GICI). 2003. The Investigation Committee for the Effects of Military Activity in the Kishon River and the Region's Waters on the Health of IDF Soldiers Activated There [in Hebrew]. Final Report. Available: http://www.tau.acJI/~bhkishon [accessed 6 May 2003].

Great Lakes Health Effects Division. 1993. Investigating Human Exposure to Contaminants in the Environment: A Handbook for Exposure Calculations. Ottowa, Ontario, Canada:Health Protection Branch, Health Canada.

Jarup L, Rogenfalt A, Binder C-G, Nogawa K, Kjellstrom T. 1983, Biological half-time of cadmium in the blood of workers after cessation of exposure. Scand J Work Environ Health 9:327-331

Richter ED, Friedman LS, Tamir Y, Berman T, Levy O, Westin JR, Peretz T. 2003. Cancer risks in naval divers with multiple exposures to carcinogens. Environ Health Perspect 111:609-617