Questioning Sources and Cardiovascular Effects of Nickel

Referencing: Cardiovascular Effects of Nickel in Ambient Air

Lippmann et al. (2006) attempted to identify subtle deleterious effects in fine airborne particulate matter (FPM), which is laudable. Nevertheless, the authors' claim (Lippmann et al. 2006) that on 14 of 103 days studied in the fall of 2004, concentrated air pollutants (CAPs) at Tuxedo, New York [near New York City (NYC)], contained "greatly elevated concentrations of nickel attributable to the Ni smelter at Sudbury, Ontario" is unsubstantiated. The Ni concentrations to which they referred (174 ng/m³) on these 14 days were concentrated 10-fold from ambient air. In other words, the Ni in ambient air at Tuxedo was actually only 17.4 ng/m³, the same as NYC (19 ng/m³).

Lippmann et al. (2006) assigned the "elevated" Ni to Inco's 381 m stack in Sudbury based on back trajectory analyses. The authors failed to account for vertical components of air parcel movement; also, by singling out one specific trajectory from the "NW wind" days, they implied much more accuracy to the back trajectories than is justified. Because meteorological data are available at 3-hr intervals, three back trajectories could be developed for each daily exposure period. Such back trajectories using the internet-based HYSPLIT model (National Oceanic and Atmospheric Administration 2006) indicate that for the 14 NW wind days, elevated Ni in CAPs on those days was more likely due to sources other than the Sudbury stack > 800 km distant. Furthermore, Inco's stack emissions are characteristic and distinct from the CAPs composition reported by Lippmann et al. (2006). Concentrations of aluminum, chromium, and iron are all 100-fold less than the concentration of Ni in Inco's emissions, whereas in CAPs on the NW wind days, the ratios of Cr:Ni and Fe:Ni, as well as those of Al:Ni and V:Ni, are similar to those of New Jersey air (Reinfelder et al. 2004). The Ni in ambient air at Tuxedo, even on the 14 NW wind days, could be easily assigned to sources surrounding NYC. Given that Tuxedo is near NYC, it should be no surprise that local sources could be large contributors to Ni in ambient FPM in Tuxedo. Although the atmospheric Ni emissions from the Sudbury stack can be transboundary and have been significant historically, the incremental contribution of Ni from Sudbury to ambient air at Tuxedo in 2004 would have been dwarfed relative to local sources. Significant reductions in emissions have been made at Inco's Sudbury operations, and air emissions from the Inco stack will diminish further as new pollution control measures are implemented.

Lippmann et al. (2006) presented two lines of evidence that Ni is the major cause of cardiovascular effects of FPM. First, exposures of ApoE^–/– mice to CAPs led them to conclude that unusually high heart rate (HR) occurred in response to elevated Ni on the NW wind days. Although the largest sustained apparent difference in HR occurred through most of December, only three NW wind days occurred in that month. Other changes in HR and heart rate variability (HRV) are either due to changes in control animals or occurred when there were no elevated Ni concentrations [see Figure 4 of Lippmann et al. (2006)]. There appears to be an error in the key of Lippmann et al.'s Figure 4 compared with the original manuscript published online: the solid lines now denote filtered air (control) instead of CAPs, and the dashed line indicates CAPs instead of control data. Given that the authors referred to the elevated HR in exposed mice, the key in the print version must be incorrect.

Considering that 2-year inhalation exposures of rodents to nickel sulfate at levels 600 times higher than those used by Lippmann et al. (2006) were without effect on mortality, the relevance of the "subtle" changes in HR and HRV requires further thought. Second, the authors "wondered if Ni may have been responsible for the notably high daily mortality" in NYC. Although it is true that NYC has a cardiovascular and respiratory (CVR) mortality coefficient that is above the national average, 34 of the 90 National Mortality and Morbidity Air Pollution Study (NMMAPS) cities have CVR mortality coefficients greater than those of NYC. Furthermore, there is no statistical relationship between NMMAPS CVR mortality rates and Ni emission rates (U.S. Environmental Protection Agency 2002).

The conclusions of Lippmann et al. (2006) contrast with the recent assessments of the Agency for Toxic Substances and Disease Registry (ATSDR 2005) and the European Union (European Chemicals Bureau 2005) that did not identify human cardiovascular risk factors for Ni. Historical monitoring within the Ni industry identified the link between high occupational exposure of certain Ni species and respiratory cancer, but no such cardiovascular risk factors have been identified after decades of occupational health monitoring.

Further research to evaluate the impacts of the constituents of FPM on cardiovascular health is justified and should continue. Nevertheless, researchers with appropriate expertise work should cooperatively in studies such as these. In this instance, Lippmann et al. (2006) would have benefitted greatly from the inclusion of atmospheric scientists on their research team.

The author is employeed by CVRD Inco Limited, the subject of the article by Lippmann et al.

References

ATSDR. 2005. Toxicological Profile for Nickel. Atlanta, GA:Agency for Toxic Substances and Disease Registry.

European Chemicals Bureau. 2005. ESIS: European Chemical Substances Information System. Available: http://ecb.jrc.it/esis/index.php?PGM=ora [accessed 8 October 2006].

Lippmann M, Ito K, Hwang JS, Maciejczyk P, Chen LC. 2006. Cardiovascular effects of nickel in ambient air. Environ Health Perspect 114:1662–1669.

National Oceanic and Atmospheric Administration. 2006. HYbrid Single-Particle Lagrangian Integrated Trajectory Model. Available: http://www.arl.noaa.gov/ready/hysp_info.html [accessed 8 October 2006].

Reinfelder JR, Totten LA, Eisenreich SJ. 2004. NJADN Final Report. Available: http://www.state.nj.us/dep/dsr/njadn/fullreport.pdf [accessed 8 October 2006].

U.S. Environmental Protection Agency. 2002. National-Scale Air Toxics Assessment for 1996: Estimated Emissions, Concentrations and Risk. Available: http://epa.gov/ttn/atw/nata/natafs5-31.pdf [accessed 8 October 2006].

---

Cardiovascular Effects of Nickel: Lippmann et al. Respond

It is readily understandable that Dutton of the International Nickel Company (INCO) would like to separate the nickel emissions from the 381-m INCO smelter stack from the highly statistically significant Ni-associated effects on heart rate and heart rate variability that we observed on 14 of 103 consecutive weekdays of exposure in our laboratory (located within the Sterling Forest State Park) in a mouse model of atherosclerosis (Lippmann et al. 2006). Indeed, it is possible that some closer source of Ni could have been responsible for the effects. However, as we noted in our article, the back trajectories on the 14 days with unusually elevated Ni concentrations did not pass over any known industrial sources or large urban areas, but did pass over or near the distant point source of Ni at the INCO smelter in Sudbury, Ontario, Canada. It is also noteworthy that the 14 back trajectories, illustrated in Figure 2 of our article (Lippmann et al. 2006), approached Sterling Forest from a variety of directions, ranging from the NW to the NNE, making it highly unlikely that that their metals compositions were influenced by a significant source within a 100-mi radius. Furthermore, both the directions of the incoming winds and the combination of unusually high Ni and lower than normal vanadium on those 14 days, as compared with the other 89 days of observation, seemed to preclude the major sources of Ni being the Port of New York, the New York City metropolitan area, or other coastal regions where residual oil is used to generate heat and electrical power. It is well known that residual oil combustion effluents are high in both Ni and V.

We commend Dutton on identifying a mislabeled key in Figure 4 of our article (Lippmann et al. 2006) that occurred during the preparation of the print version. As he noted, the original manuscript published online was correctly labeled. (See the Erratum on p. A294.)

Dutton provided no supporting reference for his comment that "2-year inhalation exposures of rodents to nickel sulfate at levels 600 times higher than those used by Lippmann et al. (2006) were without effect on mortality …." Based on the 600 concentration difference, we assume he was referring to a National Toxicology Program (NTP) report (NTP 1996). It should be noted that healthy B6C3F₁ mice were exposed in this study, and that healthy B6 mice had much greater survival times than seven other inbred mice strains when exposed to nickel sulfate by Prows et al. (2003).

Dutton also states that "there is no statistical relationship between NMMAPS [National Mortality and Morbidity Air Pollution Study] CVR [cardiovascular risk] mortality rates and Ni emission rates." Again, no reference was cited. Even if his statement was supported by a negative study, it relates to emissions and not concentrations. In our article (Lippmann et al. 2006), we showed that the annual average PM₁₀ (particulate matter < 10 µm in aerodynamic diameter) NMMAPS mortality coefficients for 60 NMMAPS cities were significantly associated with annual average ambient Ni and V concentrations in those same cities.

Finally, we take exception to Dutton's comment that implies that we lack sufficient expertise in atmospheric science. The only issue in our article that relates to atmospheric science is our use of HYSPLIT back trajectories, and we fail to see how we misused them.

The authors declare they have no competing financial interests.

References

Lippmann M, Ito K, Hwang JS, Maciejczyk P, Chen LC. (2006). Cardiovascular effects of nickel in ambient air. Environ Health Perspect 114:1662–1669.

NTP. 1996. Toxicology and Carcinogenesis Studies of Nickel Sulfate Hexahydrate (CAS No. 10101-97-0) in F344 Rats and B6C3F₁ Mice (Inhalation Studies). TR-454. Research Triangle Park, NC:National Toxicology Program.

Prows DR, McDowell SA, Aronow BJ, Leikauf GD. 2003. Genetic susceptibility to nickel-induced acute lung injury. Chemosphere 5:1139–1148.

---

Erratum

Figure 4. Daily group averaged HR (A) and HRV (logSDNN) (B) in mice exposed to CAPs or filtered air.

In Figure 4 of Lippmann et al. [Environ Health Perspect 114:1662–1669 (2006)], the key was correct in the original manuscript published online but was incorrect in the final version. The dashed lines should indicate filtered air, and the solid lines should denote CAPS. The corrected figure appears below.

EHP regrets the error.