Limits...
New views on the hypothesis of respiratory cancer risk from soluble nickel exposure; and reconsideration of this risk's historical sources in nickel refineries.

Heller JG, Thornhill PG, Conard BR - J Occup Med Toxicol (2009)

Bottom Line: In this report, we present a weight of scientific evidence examination of the human and toxicological evidence to show that soluble nickel is not carcinogenic; and, furthermore, that the carcinogenic potencies previously assigned by regulators to sulphidic and oxidic nickel compounds for the purposes of developing occupational exposure limits have likely been overestimated.An understanding of the mechanism for nickel carcinogenicity remains an elusive goal of toxicological research; as does its capacity to confirm the human health evidence on this subject with animal studies.Epidemiological methods have failed to accurately identify the source(s) of observed lung cancer risk in at least one nickel refinery (KNR).

View Article: PubMed Central - HTML - PubMed

Affiliation: James G, Heller Consulting Inc,, 1 Berney Crescent, Toronto ON, M4G 3G4, Canada. jgheller@jghcons.com.

ABSTRACT

Introduction: While epidemiological methods have grown in sophistication during the 20th century, their application in historical occupational (and environmental) health research has also led to a corresponding growth in uncertainty in the validity and reliability of the attribution of risk in the resulting studies, particularly where study periods extend back in time to the immediate postwar era (1945-70) when exposure measurements were sporadic, unsystematically collected and primitive in technique; and, more so, to the pre-WWII era (when exposure data were essentially non-existent). These uncertainties propagate with animal studies that are designed to confirm the carcinogenicity by inhalation exposure of a chemical putatively responsible for historical workplace cancers since exact exposure conditions were never well characterized. In this report, we present a weight of scientific evidence examination of the human and toxicological evidence to show that soluble nickel is not carcinogenic; and, furthermore, that the carcinogenic potencies previously assigned by regulators to sulphidic and oxidic nickel compounds for the purposes of developing occupational exposure limits have likely been overestimated.

Methods: Published, file and archival evidence covering the pertinent epidemiology, biostatistics, confounding factors, toxicology, industrial hygiene and exposure factors, and other risky exposures were examined to evaluate the soluble nickel carcinogenicity hypothesis; and the likely contribution of a competing workplace carcinogen (arsenic) on sulphidic and oxidic nickel risk estimates.

Findings: Sharp contrasts in available land area and topography, and consequent intensity of production and refinery process layouts, likely account for differences in nickel species exposures in the Kristiansand (KNR) and Port Colborne (PCNR) refineries. These differences indicate mixed sulphidic and oxidic nickel and arsenic exposures in KNR's historical electrolysis department that were previously overlooked in favour of only soluble nickel exposure; and the absence of comparable insoluble nickel exposures in PCNR's tankhouse, a finding that is consistent with the absence of respiratory cancer risk there. The most recent KNR evidence linking soluble nickel with lung cancer risk arose in a reconfiguration of KNR's historical exposures. But the resulting job exposure matrix lacks an objective, protocol-driven rationale that could provide a valid and reliable basis for analyzing the relationship of KNR lung cancer risk with any nickel species. Evidence of significant arsenic exposure during the processing step in the Clydach refinery's hydrometallurgy department in the 1902-1934 time period likely accounts for most of the elevated respiratory cancer risk observed at that time. An understanding of the mechanism for nickel carcinogenicity remains an elusive goal of toxicological research; as does its capacity to confirm the human health evidence on this subject with animal studies.

Concluding remarks: Epidemiological methods have failed to accurately identify the source(s) of observed lung cancer risk in at least one nickel refinery (KNR). This failure, together with the negative long-term animal inhalation studies on soluble nickel and other toxicological evidence, strongly suggest that the designation of soluble nickel as carcinogenic should be reconsidered, and that the true causes of historical lung cancer risk at certain nickel refineries lie in other exposures, including insoluble nickel compounds, arsenic, sulphuric acid mists and smoking.

No MeSH data available.


Related in: MedlinePlus

Vertical section through row of KNR cementation tanks shown in Figure 4. Source: Thornhill (1986) [F2].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2743697&req=5

Figure 5: Vertical section through row of KNR cementation tanks shown in Figure 4. Source: Thornhill (1986) [F2].

Mentions: KNR has a unique and eventful history that included partial destruction by fire and cessation of operation in 1918, followed by the refinery's repair and reopening only to face shutdown and bankruptcy during the twenties because of the sharp downturn in global nickel prices. Following its purchase by Falconbridge Nickel Mines Ltd in 1928, it was modernized and resumed operation in February 1930 [25]. The plant was occupied and operated by German forces from April 1940 to the cessation of hostilities in Europe in the summer of 1945. The following chart shows that, except for the shutdown in the twenties and the war period, KNR always operated more intensively (as measured in tons of nickel produced per year per hectare of land base) than PCNR (including 1961 when PCNR's production level fell by over 90%) (Figure 3). PCNR's flat topography and ample land base allowed physical separation of key buildings and horizontal process layouts. Unlike the PCNR facility, KNR's topography and foot print necessitated multi-storied building structures that either abutted each other or were connected by covered tramways linking successive process steps (Figure 4) (Figure 5) (Table 1). The schematics highlight building development, including the evolution of the Hybinette process refining steps over four time periods (i.e. 1910–29, 1930–49, 1950–69, 1970–78) [25], and support our contention of cross-contamination of KNR's electrolysis department environment by known carcinogens (sulphidic and oxidic nickel) originating within its RSC department. For example, Thornhill (1986) documented evidence, filed with the ICNCM, showing that KNR process workers received mixed dust exposures during such operations as the transfer of calcine by wheelbarrow until 1956 from KNR's roasting building to its electrolysis department [F2]. In 1954, about 150 tons per day of calcine were leached. Assuming a loading of 0.25 tons per trip, the workers would have been required to load and dump these barrows 600 times per day. Exposures to dust from these two operations would occur 1,200 times per day. After 1956, the transfer was by closed drag conveyor, which structure trapped fugitive dust that led to mixed exposures [F2].


New views on the hypothesis of respiratory cancer risk from soluble nickel exposure; and reconsideration of this risk's historical sources in nickel refineries.

Heller JG, Thornhill PG, Conard BR - J Occup Med Toxicol (2009)

Vertical section through row of KNR cementation tanks shown in Figure 4. Source: Thornhill (1986) [F2].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2743697&req=5

Figure 5: Vertical section through row of KNR cementation tanks shown in Figure 4. Source: Thornhill (1986) [F2].
Mentions: KNR has a unique and eventful history that included partial destruction by fire and cessation of operation in 1918, followed by the refinery's repair and reopening only to face shutdown and bankruptcy during the twenties because of the sharp downturn in global nickel prices. Following its purchase by Falconbridge Nickel Mines Ltd in 1928, it was modernized and resumed operation in February 1930 [25]. The plant was occupied and operated by German forces from April 1940 to the cessation of hostilities in Europe in the summer of 1945. The following chart shows that, except for the shutdown in the twenties and the war period, KNR always operated more intensively (as measured in tons of nickel produced per year per hectare of land base) than PCNR (including 1961 when PCNR's production level fell by over 90%) (Figure 3). PCNR's flat topography and ample land base allowed physical separation of key buildings and horizontal process layouts. Unlike the PCNR facility, KNR's topography and foot print necessitated multi-storied building structures that either abutted each other or were connected by covered tramways linking successive process steps (Figure 4) (Figure 5) (Table 1). The schematics highlight building development, including the evolution of the Hybinette process refining steps over four time periods (i.e. 1910–29, 1930–49, 1950–69, 1970–78) [25], and support our contention of cross-contamination of KNR's electrolysis department environment by known carcinogens (sulphidic and oxidic nickel) originating within its RSC department. For example, Thornhill (1986) documented evidence, filed with the ICNCM, showing that KNR process workers received mixed dust exposures during such operations as the transfer of calcine by wheelbarrow until 1956 from KNR's roasting building to its electrolysis department [F2]. In 1954, about 150 tons per day of calcine were leached. Assuming a loading of 0.25 tons per trip, the workers would have been required to load and dump these barrows 600 times per day. Exposures to dust from these two operations would occur 1,200 times per day. After 1956, the transfer was by closed drag conveyor, which structure trapped fugitive dust that led to mixed exposures [F2].

Bottom Line: In this report, we present a weight of scientific evidence examination of the human and toxicological evidence to show that soluble nickel is not carcinogenic; and, furthermore, that the carcinogenic potencies previously assigned by regulators to sulphidic and oxidic nickel compounds for the purposes of developing occupational exposure limits have likely been overestimated.An understanding of the mechanism for nickel carcinogenicity remains an elusive goal of toxicological research; as does its capacity to confirm the human health evidence on this subject with animal studies.Epidemiological methods have failed to accurately identify the source(s) of observed lung cancer risk in at least one nickel refinery (KNR).

View Article: PubMed Central - HTML - PubMed

Affiliation: James G, Heller Consulting Inc,, 1 Berney Crescent, Toronto ON, M4G 3G4, Canada. jgheller@jghcons.com.

ABSTRACT

Introduction: While epidemiological methods have grown in sophistication during the 20th century, their application in historical occupational (and environmental) health research has also led to a corresponding growth in uncertainty in the validity and reliability of the attribution of risk in the resulting studies, particularly where study periods extend back in time to the immediate postwar era (1945-70) when exposure measurements were sporadic, unsystematically collected and primitive in technique; and, more so, to the pre-WWII era (when exposure data were essentially non-existent). These uncertainties propagate with animal studies that are designed to confirm the carcinogenicity by inhalation exposure of a chemical putatively responsible for historical workplace cancers since exact exposure conditions were never well characterized. In this report, we present a weight of scientific evidence examination of the human and toxicological evidence to show that soluble nickel is not carcinogenic; and, furthermore, that the carcinogenic potencies previously assigned by regulators to sulphidic and oxidic nickel compounds for the purposes of developing occupational exposure limits have likely been overestimated.

Methods: Published, file and archival evidence covering the pertinent epidemiology, biostatistics, confounding factors, toxicology, industrial hygiene and exposure factors, and other risky exposures were examined to evaluate the soluble nickel carcinogenicity hypothesis; and the likely contribution of a competing workplace carcinogen (arsenic) on sulphidic and oxidic nickel risk estimates.

Findings: Sharp contrasts in available land area and topography, and consequent intensity of production and refinery process layouts, likely account for differences in nickel species exposures in the Kristiansand (KNR) and Port Colborne (PCNR) refineries. These differences indicate mixed sulphidic and oxidic nickel and arsenic exposures in KNR's historical electrolysis department that were previously overlooked in favour of only soluble nickel exposure; and the absence of comparable insoluble nickel exposures in PCNR's tankhouse, a finding that is consistent with the absence of respiratory cancer risk there. The most recent KNR evidence linking soluble nickel with lung cancer risk arose in a reconfiguration of KNR's historical exposures. But the resulting job exposure matrix lacks an objective, protocol-driven rationale that could provide a valid and reliable basis for analyzing the relationship of KNR lung cancer risk with any nickel species. Evidence of significant arsenic exposure during the processing step in the Clydach refinery's hydrometallurgy department in the 1902-1934 time period likely accounts for most of the elevated respiratory cancer risk observed at that time. An understanding of the mechanism for nickel carcinogenicity remains an elusive goal of toxicological research; as does its capacity to confirm the human health evidence on this subject with animal studies.

Concluding remarks: Epidemiological methods have failed to accurately identify the source(s) of observed lung cancer risk in at least one nickel refinery (KNR). This failure, together with the negative long-term animal inhalation studies on soluble nickel and other toxicological evidence, strongly suggest that the designation of soluble nickel as carcinogenic should be reconsidered, and that the true causes of historical lung cancer risk at certain nickel refineries lie in other exposures, including insoluble nickel compounds, arsenic, sulphuric acid mists and smoking.

No MeSH data available.


Related in: MedlinePlus