The article by Clin et al. (1) provides additional information for a
dose-response relationship with asbestos and cancer. Information where a
response curve changes effect as observed from background is critical in
establishing a safe exposure limit (threshold -exposure/concentration-
dose). Some investigators have reported this threshold is around 25
fiber/ml-years (2); although for some members of an exposed group thi...
The article by Clin et al. (1) provides additional information for a
dose-response relationship with asbestos and cancer. Information where a
response curve changes effect as observed from background is critical in
establishing a safe exposure limit (threshold -exposure/concentration-
dose). Some investigators have reported this threshold is around 25
fiber/ml-years (2); although for some members of an exposed group this may
be lower (3). However, a cumulative no-effect value does not provide
information applicable for practical every day use when monitoring worker
exposure.
Recent studies (4,5,6) have suggested levels of exposure where there
was no excess increase in cancer, notably lung cancer and mesothelioma.
This is especially noted for non-smokers where risk does not exceed unity
(lung cancer), even for high asbestos exposure, while there is a
significant increased risk for smokers and former smokers (6,7). Thus, it
appears smoking is the primary contributor and confounder of disease for
historical and current asbestos workers (6). Compounding this issue is
the high number of smokers performing asbestos abatement work
(approximately 60% or greater depending on the population observed even at
the present time) (8,9). The high rate of smoking makes it difficult to
estimate a threshold and subsequently establish an exposure value from
this type of information. Certainly, for today's asbestos workers smoking
constitutes their greatest risk (6,9,10).
Recent studies with direct (4,5) and indirect (e.g. Job Exposure Matrix
and Job Specific Modules) (6,11) exposure information do allow an estimate
of a threshold exposure dose. Although, exposure can greatly vary over
time (4), it appears even with mixed fiber exposure (chrysotile and
amphibole) (5) a threshold of 1.0 f/ml-year is applicable, but at the
upper range. If chrysotile alone is used in this estimate, it appears a
higher value would be warranted (5). Taken together, with a safety margin
to include a lower reported value in causation of asbestosis (about 23
f//ml - years) (11), a threshold of 0.8 f/ml-year would appear applicable
(20 f/ml - years). From this, using a work time period of 25 years, which
is not likely for asbestos workers in the United States, due to physical
demands of the occupation and actual length of the "industry", allows
suggestion for a threshold of 0.8 f/ml-Time Weighted Average. When
present exposure levels are included in this evaluation (12), it is
unlikely workers in developed nations will exceed a cumulative exposure of
20 or 25 fiber/ml-years. Comparison of this proposed threshold with data
reported by Clin et al., for lung cancer and mesothelioma, with 25 years
or less of exposure (table 1 in Clin et al.), provides support for this
threshold value. However, any value will be controversial, especially in
establishing a threshold.
References
1. Clin B, Morlais F, Launoy G, Guizard AV, Dubois B, Bouvier V,
Desoubeaux N, Marquignon MF, Raffaelli C, Paris C, Galateau-Salle F,
Guittet L, Letourneux M. Environ Occup Med 2011; First online March 15,
2011.
2. Lange JH. Emergence of a New Policy for Asbestos: A Result of the
World Trade Center Tragedy. Indoor and Built Environment 2004; 12:21-33.
3. Pierce JS, McKinley MA, Paustenbach DJ, Finley BL. An evaluation
of reported no-effect chrysotile asbestos exposures for lung cancer and
mesothelioma. Crit Rev Toxicol. 2008;38:191-214.
4. Sichletidis L, Chloros D, Spyratos D, Haidich AB, Fourkiotou I,
Kakoura M, Patakas D. Mortality from occupational exposure to relatively
pure chrysotile: a 39-year study. Respiration. 2009;78:63-8.
5. Dodic Fikfak M, Kriebel D, Quinn MM, Eisen EA, Wegman DH. A case
control study of lung cancer and exposure to chrysotile and amphibole at a
slovenian asbestos-cement plant. Ann Occup Hyg. 2007 51:261-8.
6. Frost G. The joint effect of asbestos exposure and smoking on the
risk of lung cancer mortality for asbestos workers (1971-2005). 2011;
Health & Safety Executive (HSE);
(http://www.hse.gov.uk/research/rrhtm/rr730.htm)
7. Frost G, Darnton A, Harding AH. The effect of smoking on the risk
of lung cancer mortality for asbestos workers in Great Britain (1971-
2005). Ann Occup Hyg. 2011 55:239-47.
8. Frost G, Harding AH, Darnton A, McElvenny D, Morgan D.
Occupational exposure to asbestos and mortality among asbestos removal
workers: a Poisson regression analysis. Br J Cancer. 2008 99:822-9.
9. Lange JH, Mastrangelo G, Buja A. Smoking and alcohol use in
asbestos abatement workers. Bull Environ Contam Toxicol 2006 77:338-42.
10. Harding A-H, Darnton A, Wegerdt J, McElvenny D. Mortality among
British asbestos workers undergoing regular medical examinations (1971-
2005). Occup Environ Med 2009;66487-495.
11. Mastrangelo G, Ballarin MN, Bellini E, Bicciato F, Zannol F,
Gioffr? F, Zedde A, Tessadri G, Fedeli U, Valentini F, Scoizzato L,
Marangi G, Lange JH. Asbestos exposure and benign asbestos diseases in 772
formerly exposed workers: dose-response relationships. Am J Ind Med 2009
52:596-602.
12. Lange JH, Sites SL, Mastrangelo G, Thomulka KW. Exposure to
airborne asbestos during abatement of ceiling material, window caulking,
floor tile, and roofing material. Bull Environ Contam Toxicol 2006 77:718-
22.
I have read with the greatest interest the convincing study on the
dose-response of cadmium ions in kidneys (1). Cadmium compounds also harm
the proteoglycan metabolism (2), and by using the urinary proteoglycan
excretion as an indicator of cadmium effects the threshold would be at 5
microg/g creatinine (3). This agrees very well with the threshold found in
the current investigation.
I have read with the greatest interest the convincing study on the
dose-response of cadmium ions in kidneys (1). Cadmium compounds also harm
the proteoglycan metabolism (2), and by using the urinary proteoglycan
excretion as an indicator of cadmium effects the threshold would be at 5
microg/g creatinine (3). This agrees very well with the threshold found in
the current investigation.
1 Chaumont A, De Winter F, Dumont X, et al. The threshold level of
urinary cadmium associated with increased urinary excretion of retinol-
binding protein and beta-2-microglobulin: a reassessment in a large cohort
of nickel cadmium battery workers. Occup Environ Med 2011; 68: 257-264
Gan et al, 2011 [1] concluded that long-term, occupational noise
exposure was associated with increased prevalence of coronary heart
disease (CHD), for which the authors report a clear exposure-response
relationship that was particularly strong for participants aged < 50
years, men and current smokers. We do not believe the results support
these conclusions, particularly in light of notable study limitations.
Gan et al, 2011 [1] concluded that long-term, occupational noise
exposure was associated with increased prevalence of coronary heart
disease (CHD), for which the authors report a clear exposure-response
relationship that was particularly strong for participants aged < 50
years, men and current smokers. We do not believe the results support
these conclusions, particularly in light of notable study limitations.
The cross-sectional design is a significant drawback. Self-reported
exposure and outcome data created uncertainty, regarding time ordering of
events. Additionally, exposed subjects had many well-known risk factors -
representing strong confounders - for cardiovascular disease (CVD)/CHD,
the effects of which cannot be entirely removed by statistical adjustment.
Moreover, unrecognized bias was likely introduced by including potential
causal intermediates and over-adjusting logistic models,[2] for which a
mechanistic basis is not well established. Although the authors dismissed
the presence of misclassification as non-differential, simulations have
shown this argument to be less persuasive.[3]
We raise additional concerns. First, heterogeneity of effect (Figure
2) precluded reporting summary estimates. It was incorrect to state, for
example, that an increased odds of CHD were observed particularly for men
when they were observed only for them. Second, the authors misapplied the
test for trend of a monotonic exposure-response relationship.[4] Finally,
potentially important effect patterns were obscured by aggregating
outcomes to ascertain CVD/CHD prevalence. CVD, the primary endpoint of
interest and the aggregate of six variables, was not discussed. The
significant association reported for CHD was largely driven by the
relatively strong association observed only for angina pectoris.
Given the prevalence of occupational noise exposure, even a modest
association would represent an important contributor to the development of
CVD/CHD. Unfortunately, Gan et al [1] does little to advance our
understanding of whether such an association exists, particularly because
the mechanism of action is so poorly understood. We agree with the authors
that cohort studies are warranted. These studies should use objective
exposure and outcome measurements.
References
1 Gan WQ, Davies HW, Demers PA. Exposure to occupational noise
exposure and cardiovascular disease in the United States: the National
Health and Nutrition Examination Survey 1999-2004. Occup Environ Med
2010;68:183-190
2 Schisterman EF, Cole SR, Platt RW. Overadjustment bias and
unnecessary adjustment in epidemiologic studies. Epidemiology 2009;20:488
-495
3 Jurek AM, Greenland S, Maldonado G. How far from non-differential
does exposure or disease misclassification have to be to bias measures of
association away from the null? Int J Epidemiol 2008; 37:382-5
4 Maclure M, Greenland S. Tests for trend and dose response:
misinterpretations and alternatives. Am J Epidemiol 1992;135:96-104
The publication of an editorial(1) and opposing commentaries(2,3)
underlines the profile OEM believes should be given to debate of the
proposal for observational epidemiologic studies and their protocols to be
registered in advance(4). I would however express my surprise that none
of these 3 offerings make mention of the workforce perspective in their
analyses of the issues. The editorial itself(1) and the commentary
o...
The publication of an editorial(1) and opposing commentaries(2,3)
underlines the profile OEM believes should be given to debate of the
proposal for observational epidemiologic studies and their protocols to be
registered in advance(4). I would however express my surprise that none
of these 3 offerings make mention of the workforce perspective in their
analyses of the issues. The editorial itself(1) and the commentary
opposing the protocol(3) do not make mention of workers at all, while the
pro-commentary(2) simply includes employees in a list of those involved in
collaboration to reduce difficulties in accessing data.
It may be possible to identify both pros and cons for the
registration proposal based on workforce issues, but to do so in this
letter would detract from its principal purpose in registering the
observation that these aspects have not been considered to date. Research
is a vital element of Occupational Health. OEM is the adopted official
Journal of the Faculty of Occupational Medicine of the Royal College of
Physicians (London). The Faculty first introduced a section dealing with
research in its ethical guidelines in 1999(5) identifying workers as key
customers of research, as well as identifying the need for clear and
detailed protocols, as well as worker consultation. As an Occupational
Physician, I am convinced that workers are owed a very real duty of care
in relation to research, whether there are clinical elements of the study
or not. The trauma and distress that research results publication and the
media response to such publication can cause a workforce, should not be
underestimated.
References
1 Loomis D. Journal Requirements to Register Observational Studies: OEM's
Policy. OEM 2011;68:83/4.
2 Rushton L. Should Protocols for Observational Research be Registered?
OEM 2011; 68:84-86.
3 Pearce N. Registration of Protocols for Observational Research is
Unnecessary and Would Do More Harm Than Good. OEM 2011; 68:86-88.
4 European Centre for Ecotoxicology and Toxicology of Chemicals. Workshop
Report, number 18: Enhancement of the Scientific Process and Transparency
of Observational Studies, 2009.
5 The Faculty of Occupational Medicine Guidance on Ethics for Occupational
Physicians, 5th Edition, May 1999.
Dr. Burstyn, in his commentary (1), underscores the critical
importance of using the best exposure assessment methods possible to
minimize misclassification. We agree about the value of expert formulated
models for systematically and transparently documenting exposure
assessment1, but caution that many existing studies may not be readily
adapted to such model building. For such studies, the best alternative
exposure ass...
Dr. Burstyn, in his commentary (1), underscores the critical
importance of using the best exposure assessment methods possible to
minimize misclassification. We agree about the value of expert formulated
models for systematically and transparently documenting exposure
assessment1, but caution that many existing studies may not be readily
adapted to such model building. For such studies, the best alternative
exposure assessment methodology should be employed, such as job-exposure
matrices (JEMs) or expert assessments of self-reported work histories.
Even though the relationships between the true exposure and estimates by
expert assessment and a JEM are unknown (which is the case for most
exposure assessments) we believe that understanding the differences
between the two methods is informative, especially given the considerable
time and resources necessary to carry out an expert assessment.
As Dr. Burstyn indicates (1), neither assessment approach used in our
study (2) allows us to claim that lead definitely causes brain tumors.
However, if this is the standard for judging the success of an exposure
assessment method, most methods are failures. Although only suggestive, we
do see some evidence of an association and indicate that future studies
would benefit from the most accurate exposure assessment method available.
The intent of our analysis was to compare two widely used approaches and
to encourage epidemiologists to pursue the best exposure assessment
methods possible. We acknowledge limitations with the expert assessment
approach and strongly support the development and use of new exposure
assessment methods. However, expert assessment may be the best approach
available to an existing study and could reveal important associations
that future studies can explore in greater detail using more refined
exposure assessment techniques.
1. Burstyn I. The ghost of methods past: exposure assessment versus
job-exposure matrix studies. Occup Environ Med 2010.
2. Bhatti P, Stewart PA, Linet MS, Blair A, Inskip PD, Rajaraman P.
Comparison of occupational exposure assessment methods in a case-control
study of lead, genetic susceptibility and risk of adult brain tumours.
Occup Environ Med 2010.
We thank Dr Triebig for his interesting comments on our article ââ¬ÅOccupational exposure to solvents and risk of lymphoma subtypes: results from the Epilymph case-control studyââ¬ï¿½.1,2 Epidemiological evidence is growing about the various etiological factors of specific lymphoma subtypes, and perhaps the different mechanisms involved.3 In our paper, we referred to previous reports suggesting an interaction o...
We thank Dr Triebig for his interesting comments on our article “Occupational exposure to solvents and risk of lymphoma subtypes: results from the Epilymph case-control study�.1,2 Epidemiological evidence is growing about the various etiological factors of specific lymphoma subtypes, and perhaps the different mechanisms involved.3 In our paper, we referred to previous reports suggesting an interaction of occupational benzene exposure with familial history of haematological diseases and history of immune system diseases,4 apparently indicating an immune system disruption as a mechanism of lymphomagenesis among benzene-exposed workers. However, while those hypotheses apply to NHL in general, we did find a positive link with CLL and dubious findings for follicular lymphoma, but not with DLBCL. It is worth commenting that immune dysfunction is reportedly more relevant for DLBCL and marginal zone lymphoma than for CLL and follicular lymphoma.3 We also referred to benzene genotoxicity as a plausible mechanism, as several genotoxic effects of benzene, and particularly, long-arm deletion of chromosome 6 and trisomy of chromosomes 2, 4, 6, 11, 12, 14 and 18, also occur among lymphoma patients.5,6
The etiologic role of benzene is well established for non-lymphocytic leukaemia, and the recent IARC re-evaluation of human carcinogens in the Monographs N. 1-99 has raised the attention for future research on other neoplasms of the lymphohaemopoietic tissue.7 A variety of combinations of multifactorial factors might plausibly intervene in the chain of events leading to each individual subtype of lymphohaemopoietic malignancies. Whether this variety of aetiological patterns is reflected by excess risk in specific time windows since exposure onset is a question perhaps too early to answer. Nonetheless, we followed Dr Triebig suggestion and explored risk of B-cell lymphoma and CLL by year of initiating exposure, whether up to 1970, between 1971 and 1980, or from 1981 onwards. As the Epilymph study started at different times in the participating countries from 1996 onwards, the 10-15 years interval indicated by Dr Triebig would fit into the last time window. While no substantial changes in risk of B-cell lymphoma were observed by time window in all exposed and in those classified with the highest confidence of exposure to benzene, risk of CLL was highest among subjects who started exposure in 1971-1980 (all exposed: OR = 2.24, 95% CI 0.98 - 5.12; high confidence: OR = 3.33, 95% CI 1.01- 11.0), it was still elevated among those whose exposure started before 1970 (all exposed: OR = 1.53, 95% CI 1.08 - 2.17; high confidence: OR = 1.52, 95% CI 0.97- 2.39), and it was not elevated among those who started exposure from 1981 onwards(all exposed: OR = 2.20, 95% CI 0.72 - 6.76; high confidence: OR = 1.27, 95% CI 0.16- 10.2). It is worth mentioning that this last group included only a tiny fraction of the exposed, mainly because of the regulatory restrictions introduced in the ‘70s. Also, subjects exposed to benzene from 1981 onwards might have been exposed to lower concentrations and for a shorter period; therefore, if cumulative dose over time were to be the correct indicator, the absence of effects might be accounted for by lower cumulative doses.
As it concerns risk associated with toluene and xylene exposure, Table 5 in our paper shows that the excess risk associated with toluene was mostly accounted for by co-occurrent exposure to benzene.2 On the other hand, the elevated risk associated with xylene exposure was generated by extremely small numbers with isolated exposure to xylene. We don’t feel confident to infer about toluene and xylene risk related to their genotoxicity, based on such poor epidemiological evidence.
Further time-related modelling of CLL risk as a function of dose of exposure to benzene, and proper stratification of overlapping exposures, would require pooled analyses of studies with high quality exposure data, an opportunity currently provided only by the Interlymph Consortium.
References
1. Triebig G. “Occupational exposure to solvents and risk of lymphoma subtypes: results from the Epilymph case-control study�. Occup Environ Med 2010; e-letter (published 7 September 2010)
2. Cocco P, t’Mannetje A, Fadda D, Melis M, Becker N, de Sanjose´ S, Foretova L, Mareckova J, Staines A, Kleefeld S, Maynadie´ M, Nieters A, Brennan P, Boffetta P. exposure to solvents and risk of lymphoma subtypes: results from the Epilymph case-control study. Occup Environ Med 2010;67:341-347.
3. Morton LM, Wang SS, Cozen W, Chatterjee N, Davis S, Severson RK, Colt JS, Vasf MA, Rothman N, Blair A, Bernstein L, Croos AJ, DeRoos AJ, Engels EA, Hein DW, Hill DA, Kelemen LE, Lim U, Lynch CF, Schenk M, Wacholder S, Ward MH, Hoar Zahm S, Chanock SJ, Cerhan JR, Hartge P. Etiologic heterogeneity among non-Hodgkin lymphoma subtypes. Blood 2008;112:5150-60.
4. Vineis P, Miligi L, Seniori Costantini A. Exposure to solvents and risk of non-Hodgkin lymphoma: clues on putative mechanisms. Cancer Epidemiol Biomarkers Prev 2007;16:381-4.
5. Zhang L, Rothman N, Li G, Guo W, Yang W, Hubbard AE, Hayes RB, Yin S, Lu W, Smith MT. Aberrations in chromosomes associated with lymphoma and therapy-related leukemia in benzene-exposed workers. Environ Mol Mutagen 2007;48:467-74.
6. McHale CM, Lan Q, Corso C, Li G, Zhang L, Vermeulen R, Curry JD, Shen M, Turakulov R, Higuchi R, Germer S, Yin S, Rothman N, Smith MT.. Chromosome translocations in workers exposed to benzene. J Natl Cancer Inst Monogr 2008;39:74-7.
7. Baan R, Grosse Y, Straif K, Secretan B, El Ghissassi F, Bouvard V, Benbrahimm-Tallaa L, Guha N, Freeman C, Galichet L. A review of human carcinogens – Part F: Chemical agents and related occupations. Lancet Oncology 2009;10:1143-4.
Conflict of Interest: None Declared
In his letter, Predicting chemicals causing cancer in animals as
human carcinogens (Occup Environ Med 2010;67:720), Huff surprisingly finds
opportunity to promote long-term carcinogenesis bioassays using animals in
response to an editorial by Suarthana et al (Occup Environ Med
2009;66:713e14), Predicting occupational diseases. In their editorial,
Suarthana et al generalize from the development of diagnostic models to
pred...
In his letter, Predicting chemicals causing cancer in animals as
human carcinogens (Occup Environ Med 2010;67:720), Huff surprisingly finds
opportunity to promote long-term carcinogenesis bioassays using animals in
response to an editorial by Suarthana et al (Occup Environ Med
2009;66:713e14), Predicting occupational diseases. In their editorial,
Suarthana et al generalize from the development of diagnostic models to
predict sensitisation to occupational allergens. Suarthana et al mention
no animal studies and conclude that "[t]here is now an opportunity to
develop prediction models for diverse occupational diseases, especially
given the existing large epidemiological studies."
Huff asserts that "findings from independently conducted bioassays on
the same chemicals are consistent[.]" In fact, a comparison of 121
bioassays from the U.S. National Toxicology Program (NTP) database with
those in the published scientific literature found that the studies
produced consistent results only 57 percent of the time.[1] Huff also
claims that "less than10% of all chemicals if evaluated in bioassays would
be predicted to be carcinogenic." In our analysis of more than 500 NTP
bioassays, we show that more than half of the substances evaluated
produced evidence of carcinogenicity in at least one group of animals.[2]
The high false positive rate is thought to be an indirect effect of
increased cell proliferation in response to cell injury and death caused
by the near toxic doses of test substances used.[3] Huff observes that
there are more similarities than differences between rodents and humans.
However, well-characterized species-specific modes of action not operating
in humans also contribute to the high rate of false positives.[4]
The time has come for antiquated animal tests like the bioassay to be
abandoned in favor of modern, human-relevant methods such as the
epidemiological studies recommended in Suarthana et al's editorial, high-
throughput in vitro methods, and computational toxicology.
[1] Gottmann E, Kramer S, Pfahringer B, et al. Data quality in
predictive toxicology: reproducibility of rodent carcinogenicity
experiments. Environ Health Perspect 2001;109:509-14.
[2] PETA. Wasted money, wasted lives: A layperson's guide to the
problems with rodent cancer studies and the National Toxicology Program.
Norfolk, VA: People for the Ethical Treatment of Animals. 2006.
http://www.mediapeta.com/peta/pdf/Wasted-money-PDF.pdf (accessed 17 Sept
2010).
[3] Gaylor DW. Are tumor incidence rates from chronic bioassays
telling us what we need to know about carcinogens? Regul Toxicol Pharmacol
2005;41:128-33.
[4] Cohen SM. Human carcinogenic risk evaluation: an alternative
approach to the two-year rodent bioassay. Toxicol Sci 2004;80:225-9.
Conflict of Interest:
Conflict of Interest:
The author is employed by People for the Ethical Treatment of Animals.
Considering the temporal association between exposure to benzene and
the later development of leukaemia it is questionable if this phenomena is
also true for NHL.1 From several independent epidemiologic studies with
consistent findings it can be concluded, that 10 to 15 years after
exposure to benzene has been stopped, the risk of leukaemia is
significantly less or even absent.2,3,4
Considering the temporal association between exposure to benzene and
the later development of leukaemia it is questionable if this phenomena is
also true for NHL.1 From several independent epidemiologic studies with
consistent findings it can be concluded, that 10 to 15 years after
exposure to benzene has been stopped, the risk of leukaemia is
significantly less or even absent.2,3,4
Assuming that the underlying mechanism for leukaemia and NHL is the
same, it would be important to use the large database of the "Epilymph
study" to analyze the temporal pattern between exposure and disease.
The study found increased risks for chronic lymphocytic leukaemia
after exposure to toluene and xylene. A benzene exposure was excluded.
These statistical associations must be discussed with respect to the
genotoxicologic evidence of these aromatic hydro-carbons. Compared to
benzene, toluene and xylene have not been proven as human carcinogens. The
IARC Working Group concluded in 1999, that there is inadequate evidence in
humans for the carcinogenicity of toluene and xylenes.5 Therefore the
associations must be interpreted with caution and do not support
causality.
Literature:
1. Triebig G. Implications of latency period between benzene exposure and
development of leukemia - a synopis of literature. Chem Biol Interact
2010; 184: 26-29.
2. Hayes RB, Song-Nian Yin, Dosemeci M. Benzene and the dose related
incidence of hematologic neoplasm in China. J Natl Cancer Inst 1997; 89:
1065-1071.
3. Finkelstein MM. Leukemia after exposure to benzene: temporal trends and
implications for standards. Am J Ind Med 2000; 38: 1-7.
4. Glass DC, Sim MR, Fritschi L, Gray CN, Jolley DJ, Gibbons CG. Letter to
the editor. Leukemia risk and relvant benzene exposure period. Am J Ind
Med 2002; 42:481-489
5. IARC Monographs on the evaluation of carcinogenic risks to humans. Re-
evaluation of Some Organic Chemicals, Hydrazine and Hydrogen Peroxide.
Volume 71, Part two (Toluene) and Part three (Xylene). World Health
Organization International Agency for Research on Cancer, 1999
Correspondence to:
Prof. Dr. G. Triebig, M.D., M.Sc.
Institute and Outpatient Clinic for
Occupational and Social Medicine
University of Heidelberg
Vossstr. 2
D-69115 Heidelberg
Germany
Tel.: ( 49) 6221 56 51 01
Fax: ( 49) 6221 56 29 91
Email: GTriebig@med.uni-heidelberg.de
Within the Introduction the authors wrongly state that 4-chloro-ortho
-toluidine is present in cigarette smoke. Whereas ortho-toluidine has been
repeatedly reported to be present in cigarette smoke, this has never been
reported for 4-chloro-ortho-toluidine. ortho-Toluidine has also been
implicated in bladder cancer in the rubber industry (Baan et al. Lancet
Oncol. 9:322-323, 2008) and this was corroborated by results of a...
Within the Introduction the authors wrongly state that 4-chloro-ortho
-toluidine is present in cigarette smoke. Whereas ortho-toluidine has been
repeatedly reported to be present in cigarette smoke, this has never been
reported for 4-chloro-ortho-toluidine. ortho-Toluidine has also been
implicated in bladder cancer in the rubber industry (Baan et al. Lancet
Oncol. 9:322-323, 2008) and this was corroborated by results of a
biomonitoring study (Ward et al. J.Natl.Cancer Inst. 88:1046-1052, 1996).
In the Discussion/Conclusion a comment on the possibility to pinpoint
possibly relevant exposure to known bladder carcinogens by biomonitoring
is missing.
We read with great interest the recent publication by Boers et al
(2010), in which they presented updated mortality results from an
occupational cohort of Dutch chlorophenoxy herbicide manufacturing
workers. The previous follow-up from this cohort (Hooiveld et al, 1998)
reported a statistically significant dose-related increase in mortality
from ischemic heart disease (IHD) with increasing levels of modeled TCDD
exposur...
We read with great interest the recent publication by Boers et al
(2010), in which they presented updated mortality results from an
occupational cohort of Dutch chlorophenoxy herbicide manufacturing
workers. The previous follow-up from this cohort (Hooiveld et al, 1998)
reported a statistically significant dose-related increase in mortality
from ischemic heart disease (IHD) with increasing levels of modeled TCDD
exposure. The relative risks in the medium and high TCDD exposure
categories compared to the low category were 1.5 (95% CI 0.7-3.6) and 2.3
(95% CI 1.0-5.0), respectively (Hooiveld et al, 1998). The earlier study
was cited in our recent literature review of cardiovascular disease
mortality in relation to dioxin exposure (Humblet et al, 2008).
In the present publication (Boers et al, 2010) the authors concluded
that the observed associations between occupational exposure and IHD were
attenuated compared with those found in their previous analysis. However,
in their recent paper they did not present the updated results for IHD
from the analysis of modeled TCDD. The authors explained that they did not
use the earlier TCDD model approach because it was available only for one
of the two factories in the study, and furthermore was based on a small
number of blood samples. These considerations notwithstanding, we believe
that it would be important to provide the updated modeled TCDD results
both for IHD and all circulatory disease. At a minimum it would provide
comparability with the previous findings from their study. Furthermore,
future literature reviews on cardiovascular disease and TCDD would then be
able to include this information, providing guidance for future dioxin
risk assessments. This is especially important since the suggestion of an
increased IHD risk persisted in the updated results that were presented,
i.e. a statistically non-significant increased IHD relative risk of 1.6
(95% CI 0.72-3.55) among the workers exposed to a 1963 accidental release
of dioxins. These workers would be expected to be among the highest
exposed of all the workers.
O Humblet, R Hauser
Correspondence to: Mr. O Humblet, Department of Environmental Health,
Harvard School of Public Health, Boston, Massachusetts, USA;
ohumblet@hsph.harvard.edu
References
Boers D, Portengen L, Bueno-de-Mesquita HB, Heederik D, Vermeulen R.
Cause-specific mortality of Dutch chlorophenoxy herbicide manufacturing
workers. Occup Environ Med. 2010 Jan;67(1):24-31.
Hooiveld M, Heederik DJ, Kogevinas M, Boffetta P, Needham LL,
Patterson DG Jr, Bueno-de-Mesquita HB. Second follow-up of a Dutch cohort
occupationally exposed to phenoxy herbicides, chlorophenols, and
contaminants. Am J Epidemiol. 1998 May 1;147(9):891-901.
Humblet O, Birnbaum L, Rimm E, Mittleman MA, Hauser R. Dioxins and
cardiovascular disease mortality. Environ Health Perspect. 2008
Nov;116(11):1443-8.
The article by Clin et al. (1) provides additional information for a dose-response relationship with asbestos and cancer. Information where a response curve changes effect as observed from background is critical in establishing a safe exposure limit (threshold -exposure/concentration- dose). Some investigators have reported this threshold is around 25 fiber/ml-years (2); although for some members of an exposed group thi...
Dear Editor,
I have read with the greatest interest the convincing study on the dose-response of cadmium ions in kidneys (1). Cadmium compounds also harm the proteoglycan metabolism (2), and by using the urinary proteoglycan excretion as an indicator of cadmium effects the threshold would be at 5 microg/g creatinine (3). This agrees very well with the threshold found in the current investigation.
1 Cha...
Gan et al, 2011 [1] concluded that long-term, occupational noise exposure was associated with increased prevalence of coronary heart disease (CHD), for which the authors report a clear exposure-response relationship that was particularly strong for participants aged < 50 years, men and current smokers. We do not believe the results support these conclusions, particularly in light of notable study limitations.
...The publication of an editorial(1) and opposing commentaries(2,3) underlines the profile OEM believes should be given to debate of the proposal for observational epidemiologic studies and their protocols to be registered in advance(4). I would however express my surprise that none of these 3 offerings make mention of the workforce perspective in their analyses of the issues. The editorial itself(1) and the commentary o...
Dr. Burstyn, in his commentary (1), underscores the critical importance of using the best exposure assessment methods possible to minimize misclassification. We agree about the value of expert formulated models for systematically and transparently documenting exposure assessment1, but caution that many existing studies may not be readily adapted to such model building. For such studies, the best alternative exposure ass...
In his letter, Predicting chemicals causing cancer in animals as human carcinogens (Occup Environ Med 2010;67:720), Huff surprisingly finds opportunity to promote long-term carcinogenesis bioassays using animals in response to an editorial by Suarthana et al (Occup Environ Med 2009;66:713e14), Predicting occupational diseases. In their editorial, Suarthana et al generalize from the development of diagnostic models to pred...
Considering the temporal association between exposure to benzene and the later development of leukaemia it is questionable if this phenomena is also true for NHL.1 From several independent epidemiologic studies with consistent findings it can be concluded, that 10 to 15 years after exposure to benzene has been stopped, the risk of leukaemia is significantly less or even absent.2,3,4
Assuming that the underlying...
Within the Introduction the authors wrongly state that 4-chloro-ortho -toluidine is present in cigarette smoke. Whereas ortho-toluidine has been repeatedly reported to be present in cigarette smoke, this has never been reported for 4-chloro-ortho-toluidine. ortho-Toluidine has also been implicated in bladder cancer in the rubber industry (Baan et al. Lancet Oncol. 9:322-323, 2008) and this was corroborated by results of a...
We read with great interest the recent publication by Boers et al (2010), in which they presented updated mortality results from an occupational cohort of Dutch chlorophenoxy herbicide manufacturing workers. The previous follow-up from this cohort (Hooiveld et al, 1998) reported a statistically significant dose-related increase in mortality from ischemic heart disease (IHD) with increasing levels of modeled TCDD exposur...
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