Excerpt from Center for Disease Control and Prevention (CDC) official document on COVID-19

https://www.cdc.gov/coronavirus/2019-nCoV/lab/index.html

The CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel is a real-time RT-PCR test intended for the qualitative detection of nucleic acid from the 2019-nCoV in upper and lower respiratory specimens (such as nasopharyngeal or oropharyngeal swabs, sputum, lower respiratory tract aspirates, bronchoalveolar lavage, and nasopharyngeal wash/aspirate or nasal aspirate) collected from individuals who meet 2019-nCoV clinical and/or epidemiological criteria (for example, clinical signs and symptoms (the difference between signs and symptoms?) associated with 2019-nCoV infection, contact with a probable or confirmed 2019-nCoV case, history of travel to geographic locations where 2019-nCoV cases were detected (except Antarctica and Arctica in the pandemia?) , or other epidemiologic links (couple examples ?) for which 2019-nCoV testing may be indicated as part of a public health investigation). Testing in the United States is limited to laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. § 263a, to perform high complexity tests. Results are for the identification of 2019-nCoV RNA. The 2019-nCoV RNA is generally detectable in upper and lower respiratory specimens during infection. Positive results are indicative of active infection with 2019-nCoV but do not rule out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease. Laboratories within the United States and its territories are required to report all positive results to the appropriate public health authorities. Negative results do not preclude 2019-nCoV infection and should not be used as the sole basis for treatment or other patient management decisions. Negative results must be combined with clinical observations, patient history, and epidemiological information.

Bold, italics, and question mark are mine.

Many question marks are in the CDC official document. When the notion of testing, testing, testing became one of the main ways of solving the COVID-19 epidemic, the information of positive or negative 2019-nCoV tests reliability is essential. CDC ought to provide this information without hiding behind general statement.

Reflections on Formaldehyde Carcinogenicity

Formaldehyde carcinogenicity is now a commonly accepted notion in society, as well as in anatomic pathology laboratories. Guilty on arrival. However, the background of this concept is far beyond a reasonable doubt.

There is not now even an echo politically charged dispute of 1980s between U.S. Environment Protection Agency (EPA), Occupational Safety & Health Agency (OSHA), College of American Pathologists (CAP), Formaldehyde Institute, DuPont, and labor unions on the evaluation of formaldehyde occupational exposure risk, which was based on the assessment of formaldehyde as “probable carcinogen” at that time. 1 In 1989, the American Medical Association (AMA) summarized the literature data through 1985 on occupational exposure to formaldehyde. Mentioning that regulatory agencies as OSHA, regarded formaldehyde as a possible human carcinogen, AMA observed that “this is a controversial opinion in the view of many industry and academic scientists.”1

Times have changed. The main organization influencing the assessment of reagents as carcinogenic is the World Health Organization’s (WHO) International Agency for Research on Cancer (IARC) based in Lyon, France. IARC summarizes literature data predominantly epidemiological research, as well as some experimental studies. According to IARC Press Release No 153, 15 June 2004 formaldehyde is placed in Group I – known carcinogens- along with such substances as asbestos and benzene.2 The dispute is over.

However, the Monograph Programme, the IARC’s main document, presents cohort and case-control epidemiological studies predominately manufacturing and garment industries, as well as exposure in mobile homes to formaldehyde- containing materials.3 The main conclusions are based on studies of industrial workers, although there is a group of professionals which included pathologists, anatomists, and funeral homes workers. The data are quite contradictory due to the misclassification and the inadequate methodology of the dose-response relationship. Most data represent epidemiological studies, including cohort analyses which cannot be now repeated due to changes in manufacturing and environment.

There are conflicting literature data on this subject which cast doubt that the IRAC conclusion is balanced and can be accepted as a scientific fact. Despite attempts of scientific objective discussion, there is a trend to leave out some publications and opinions that contradict the group’s conclusion.4-9 Most references reflect data before 80th even if the articles are published after 2000. The long list of references represents limited groups of authors which publish articles in different combinations.

There is a discrepancy between the statistical epidemiological data and minimal clinical evidence from physicians who observed particular or groups of patients. Neither otolaryngology, nor other surgical manuals even mention formaldehyde as a possible ethological or contributing factor of cancer in their clinical observations. The fundamental “Cancer Principles and Practice of Oncology” do not mention formaldehyde either in carcinogenicity or in other clinical chapters (head and neck, lung).10Pathologists haven’t observed higher morbidity or mortality of colleagues and technical staff in contact with formalin. (See details at post “Formaldehyde carcinogenicity as safety concern” at Safety section).

The divide regarding formaldehyde carcinogenicity has a remote analogy with global warming/climate change. Nobody dare to challenge this notion. The deleterious effect of formaldehyde makes carcinogenicity so obvious that it is even impolite to question its credibility.

In practical sense, however, the dispute over formaldehyde carcinogenicity is meaningless at this time. We have to accept the conclusion of IARC until it is proven wrong. Moreover, there is barely a chance that such studies will be conducted in the foreseeable future. The USA regulatory agencies, the EPA and the OSHA assume formaldehyde as a potential occupational carcinogen with appropriate regulations. 1 OSHA mandated the notice in any laboratory or industrial area where formaldehyde mixtures or solutions capable of releasing formaldehyde into the air at concentrations reaching exceeding 0.1 ppm are used:” Danger: Formaldehyde: irritant and potential cancer hazard.”

Manufacturers have accepted regulation and measure improvements in the work place environment, instead of engaging in costly altercations with the EPA and lawyers, as well as sustaining public relation losses with the aggressive coverage on formaldehyde carcinogenicity subject by the mainstream media. The American Conference of Governmental Industrial Hygienists (ACGIH) has more stricter requirements for time weighted average (TWA) short-term-exposure limit (STEL) (0.3 ppm) than OSHA (2 ppm), although the recommended exposure limits do not have a legal application in the USA in opposite to OSHA. It is remarkable that the ACGIH 0.3 ppm limit is set on irritation, not carcinogenicity.

Clinical laboratories and other facilities (anatomical, research) have accepted the OSHA requirement for 8 hours time weighted average Permissible Exposure Limit (PEL) of 0.75 ppm. There is not in public domain 8 hours TWA by the ACGIH. The management of local laboratories accepts this measure without any question. The institution’s authorities would not forgive the laboratory management’s failure to meet these relatively simple requirements because there would be some consequences of accreditation which nobody needs.

This rosy picture, however, obscures very important question. The regularly scheduled monitoring reflects more or less the general environment in the work place but the devil of formaldehyde exposure is in the details of every day work practices– how the splashes and spills are handled, as well as wet specimen disposal; this is when the most overexposure occurs, but nobody monitors and even pays attention. The everyday practice occurrences of overexposure are more important than quite theoretical carcinogenicity.

During overexposure, the workers lose, temporally or permanently due to sensitization, the natural defense of the upper respiratory tract or skin. Given by evolution, both are, especially upper respiratory area (nasal mucosa, paranasal sinuses, conches) with the tiny cilia movement mechanism, very important immunological line of defense not only against pathogenic infection although the latter is the main beneficiary. (See more details in ”Formaldehyde exposure safety rationale” in the Safety section  ).

Toxicity of formaldehyde overexposure is not urban legend. Due to my silly behavior during a cleanup of a formalin spill, I lost once my voice for a week. Of course, it was a chemical injury. However, some “micro burns” occur in practice on a permanent basis. For example, when the working tissue processor is opened for some reasons (add/take out a cassette/s, check something, etc.)in formalin phase a vapor of formaldehyde from the warm formalin goes in the person’s breathing area. Separation of specimens from formalin during specimen disposal is a different example. In my pathology youth, I had many eye injuries by formalin splashes.

Regarding formaldehyde carcinogenicity everyone is entitled to his/her opinion, especially the question is unsolvable at this stage of society’s development.

In my opinion, this is an unproven concept. However, the harmful effect of formaldehyde exposure is indisputable. Efforts should be concentrated as much as possible on the prevention of negative consequences, by improving working conditions, introducing and following safe work practices. It should be made clear to everyone that personal responsibility is matter of paramount importance.

(See also posts “Monitoring formaldehyde exposure ”, “Formalin Spills and Splashes”, as well as the summarized article”Formalin safety in the surgical pathology laboratory” in the Safety section. Although the article is too long for a website, it provides a comprehensive approach to formalin safety topics that are presented in separate website’s posts. It is an “uncensored by reviewers” variant of the article which has been published in LabMedicine in 2009 )

References

1. Council Report. Formaldehyde.  Council on Scientific Affairs. JAMA 1989; 261:1183-1187

2.  IARC Press Release No 153, 15 June 2004

3. World Health Organization International  Agency for Research on Cancer IARC Monographs on the Evaluation Carcinogenic Risks on Humans Volume 88 , 2006 Formaldehyde Monographs Programme  http://monographs.iarc.fr/ENG/Monographs/Vol88/index.php

4.  Collins JJ, Acquavella JF, Esmen NA: An Updated Meta-Analysis of Formaldehyde Exposure and Upper Respiratory Tract JOEM, Vol 39, Number 7, July 1997: 639-651

5.  Gardner MJ, Pannett B., Winter PD, Crudas AM.  A cohort study of workers exposed to formaldehyde in the British chemical industry: an update British Journal of Industrial Medicine 1993; 50: 827-834

6. McLaughlin JK. Formaldehyde cancer: a critical review. Int Arch Occup Environ Health (1994) 66: 295-301

7. Chang ET. Adami HO The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol. Biomarkers Prev, 2006; 15 (10); 1765-1977

8. Hauptman M, Lubin JH, Stewart PA, Hayes RB, Blair A: Mortality from solid cancers among Workers in Formaldehyde Industries. American Journal of Epidemiology, 159; (12): 1117-1130

9. C. Bosetti C, McLaughlin JK, Tarone RE, Pira E and La Vecchia C: Formaldehyde and cancer risk: a quantative review of cohort studies through 2006. Annals of Oncology 2008; 19; (1): 29-43

10. DeVita VT, Hellman S, Rosenberg SA. Cancer: Principles and Practice of Oncology.  Lippincott Williams & Wilkins 7th Ed, 2008

 

 

 

 

 

 

 

Controversy of Infection Exposure in Surgical Pathology

While working in anatomical pathology in different positions, I gradually developed more serious attitude towards many aspects of safety, especially infectious exposure. This change occurred in parallel with changes in the surgical pathology laboratory environment.

Specimens are more often grossed when in the fresh state. The amount of frozen sections has increased dramatically. Central air-conditioning is a friend but it might be an enemy if the around pathogenic microorganisms are dispersed in aerosol form in the case that the laboratory rooms are not meticulously cleaned by “scheduled” housekeeping.

On the other hand, are not the harmful effects of infection exposure in the surgical pathology laboratory exaggerated? Do we have sufficient data to support the protective measures such as wearing PPE that cost money and impose “hardship” while wearing them? These questions cannot be dismissed without further clarification, but there is a controversy. We do not have data of increased infectious diseases in the surgical pathology laboratory 1,2,3,4,5.

In fact, microbiology laboratory data are the focus of the most biosafety literature.  It has been reported that the risk for laboratory-acquired infections in the microbiology laboratory is higher than that for the general population. However, these data cannot be extrapolated to the surgical pathology laboratory for the obvious reason that the latter does not handle microorganism cultures. In a surgical pathology laboratory, the infectious material is dispersed at incomparably lower concentrations, although, unfortunately, in the potentially dangerous aerosol form.

In the surgical pathology laboratory, the clarification of the controversy will be never completed for two reasons. First, the amount of infectious material might not be enough to generate a clinically apparent disease that can be included in significant statistics. Second, fortunately, the OSHA requirements will prevent laboratories from collecting data for statistically reliable cohort studies. If a laboratory worker contracts tuberculosis (TB), a single occurrence would not prove anything.  I performed dozens of autopsies on cadavers with cavernous lung tuberculosis wearing only a lab coat and gloves on. I remained TB negative; nevertheless, this does not suggest that TB encounters are harmless.

There might be some disputable approaches to the effects of infection exposure in the surgical pathology laboratory (see in “Immunological perspective of infection exposure in surgical pathology laboratory” ).

Does the controversy matter? While working in the surgical pathology laboratory, it does not make sense to risk exposure to infection. Implementation of the OSHA Bloodborne Pathogens Standard through rational work practices with personal responsibility is the key.

(See these issues in the summarized form in “Prevention of Infection Exposure  in HistologyLaboratory” article in Safety section  of our book Grossing Technology (Amazon.com).

References

1. Pike RM. Laboratory-associated infection: incidence, fatalities, causes, and prevention. Annu Rev Microb. 1979; 33: 41-66.

2. Sewell DL. Laboratory associated infections and biosafety. Clin Microbiology Rev. 1995; 8: 389-405.

3  Walker D and Campbell D.  A survey of infections in United Kingdom laboratories, 1994-1995. J Clin Pathol. 1999; 52: 415-418.

4. Lim PL, Kurup A, Gopalakrishna G. et al. Laboratory-acquired severe acute respiratory syndrome. N Engl J Med. 2004; 350:1740-5.

5. Singh K. Laboratory-Acquired Infections. Clin Infect Disease. 2009; Jul 1; 49(1):142-7.