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Abstract

The American Conference of Governmental and Industrial Hygienists (ACGIH^®) states “…the TLV^®-CS Committee preferably relies on published, peer-reviewed literature available in the public domain.” Many studies used to document threshold limit values (TLVs) are not peer reviewed, with many unpublished. The academic studies published in the peer-reviewed literature upon which ACGIH relies to determine TLVs rarely report data not already statistically transformed and thus incalculable. From 2008 to 2018, ACGIH established or reviewed TLVs for 145 different substances or groups of substances. Studies underlying development of these 145 TLVs demonstrate limited reporting of data sufficient to facilitate independent statistical analysis. None of the 145 TLVs showed sufficient data to independently substantiate ACGIH’s evaluations. In the majority of cases, sentinel studies upon which calculation of the TLV was based cannot be determined. Occupational Safety and Health Administration (OSHA) recommends workplaces rely on ACGIH TLVs and National Institute for Occupational Safety and Health recommended exposure limits rather than older OSHA permissible exposure limit values to optimize worker safety. Inaccurate or poorly substantiated determination of TLVs can adversely affect both human health and commerce, as net US sales of the 145 substances represent an estimated USD$189 billion, about one-fourth of the USD$800 billion chemical market in the United States. ACGIH should provide the studies relied upon, individual data values supporting the TLVs, and statistical calculation methods underlying the development of a TLV. The current system of poorly supported and underreported TLVs has the potential to propagate errors into the standard setting process of other regulatory organizations both nationally and internationally, as the ACGIH TLVs are used by many foreign regulatory bodies. Increased transparency by ACGIH is consistent with recent reforms implemented by US EPA.

Keywords

ACGIH TLV years 2008–2018 economic impact non-transparency inconsistency

Background

The American Conference of Governmental and Industrial Hygienists (ACGIH^®)) has been setting threshold limit values (TLVs^®) for chemicals used in industry for over 72 years. The TLVs are reviewed and updated annually by a committee of health professionals who have stated that, “These values are based on the best available information from industrial experience, from experimental studies and, when possible, from the combination of both”.¹ Additionally, ACGIH has stated that these limits are set at a level to protect “nearly all workers” from adverse health effects over their working lifetimes.² However, the documentation supporting the implementation of this position is quite limited.^3,4 In addition, the subjective considerations by ACGIH illustrated by their phraseology “nearly all workers” and “a small percentage of workers may experience discomfort from substances at concentrations at or below the threshold limit…” leave room for interpretative license from substance to substance and expert panel to expert panel.

For at least 30 years, scientific articles have been critiquing ACGIH regarding the methods employed to develop TLVs.^5
–7 There has also been commentary regarding the inadvisability of adopting TLVs as official limits by the Occupational Safety and Health Administration (OSHA) and other countries around the world.⁵ Additionally, some authors have posited that industry has played too important a role in the setting of TLVs.^5

–8 In 1990, Roach and Rappaport postulated that TLVs were being driven directionally more by considerations of actual exposures in industry rather than by strict assessment of human health hazards.⁷ Specifically, as exposures in industry were reduced via improved technologies or better workplace practices, TLVs were concomitantly lowered. Roach and Rappaport⁷ and Nelson⁹ showed that TLVs reflect attainable exposures at the time of implementation and that the trajectory of TLVs tracks the decline of exposures to industrial chemicals over time.

Roach and Rappaport⁷ reviewed the 1976 and 1986 Documentation of the TLVs for Chemical Substances (TLV-CSs) to determine the basis for the TLVs.^3,4 Upon evaluating the documentation, they found that the TLV Committee has traditionally emphasized studies involving human exposures. In the 1976 Documentation,³ 225 of the 488 (46%) TLVs listed were at least partly based on human exposures. In contrast, in the 1986 Documentation,⁴ only 127 of the 600 (21%) chemicals listed were at least partly based on human exposures. The trend toward decreasing emphasis being placed on human workplace exposures continues today.

Careful analysis by Roach and Rappaport⁷ of the data available from the original references cited by the TLV Committee found that 17% of employees exposed to a concentration at or below the 1976 TLV³ and 14% of employees exposed at or below the 1986 TLV⁴ reported adverse effects. These results suggest an overall risk of exposure beyond the recommended workplace air level of between 1 in 6 and 1 in 7. According to Roach and Rappaport,⁷ this result was inconsistent with the TLVs, representing levels sufficient to protect “nearly all workers” from adverse health effects over their working lifetimes.¹

Rappaport⁸ also showed that the TLVs positively correlated with the levels of exposure reported in the studies cited by the TLV committee in its documentation. Based on this colinearity, Roach and Rappapport⁷ concluded that the TLVs reflected the exposure levels at the time the limits were adopted. Castleman and Zeim⁵ have alleged that the colinearity between the achievability and the actual threshold value set suggests that corporations unduly influenced the setting of TLVs through personal communications with the ACGIH Committee. (A less pejorative interpretation of this colinearity is that requiring achievement of an exposure standard for which technology is not currently available within a feasible cost range is not practical if the compound under consideration is necessary and cannot be replaced. In these instances, use of personal protective equipment by all workers within the exposure zone can sometimes be needed.) The ACGIH Board of Directors responded by stating that they solicited information from all possible sources through the Notice of Intended Changes.¹ The Board also stated that the analysis of Rappaport⁸ suffered from bias introduced by reliance on a “small non-representative sample of TLVs…”.¹⁰ Rappaport and Roach¹¹ countered that their statistical sample was not biased merely because of limited size because inclusion and consideration of all pertinent studies cited in the Documentation represented a generalizable subsample of TLVs as a whole.

Rappaport⁸ extended this line of investigation and analyzed reductions in TLVs as a function of time for 27 substances in the “Notice of Intended Changes (for 1991–1992)”.¹² The result of his analysis showed overall median-fold reductions of 2.0–2.5 between 1946 and 1989. In 1993, Nelson⁹ completed a detailed analysis of all 630 TLVs as a whole, industry-specific TLVs, and TLVs for known or suspected carcinogens. For each category of TLV, Rappaport⁸ determined the rate of change of TLVs between 1946 and 1990 and found the median-fold reduction for all TLVs to be 2.0. For most industries in this analysis, the TLV reduction was also 2.0-fold, and for known or suspected carcinogens, the TLV reduction was 2.4-fold. The rate of change for all TLVs decreased with time (21.7% reductions per year in 1951 to 13.3% per year in 1990). For most industries, the reduction rate was 13.3% reductions per year, while for known or suspected carcinogens, it was 16% per year (over this period of time). He postulated that the results of this analysis could be used to infer past exposures.

Over the last several years, the existence of a replicability crisis in the biomedical literature has become widely recognized.¹³ The replicability crisis has elevated the essentiality of transparency in any data-based process upon which important decisions rely. To the best of our knowledge, the current investigation introduced below represents the most comprehensive analysis of the lack of transparency in the ACGIH TLV process. Recently, we addressed the lack of transparency in the ACGIH TLV process.¹⁴ The current analysis extends the previous study by examining every TLV set during the 10-year interval between 2008 and 2018.

Introduction

ACGIH TLVs levels are extremely influential. ACGIH TLVs were in widespread industrial hygiene practice for many years before any other workplace exposure limits were established.¹⁵ The OSHA requires the ACGIH TLV to be listed on Safety Data Sheets.¹⁶ OSHA recommends that its own legally binding permissible exposure limits (PELs) not be considered but rather that other exposure limit recommendations including the ACGIH TLV guide workplace safety standards.¹⁷ The ACGIH TLV directly influences the following: selection and use of personal protective equipment, installation of workplace ventilation equipment, monitoring of workplace air levels, decisions by customers as to the particular chemical selected for a given industrial application or process, decisions by chemical manufacturers regarding whether to produce a particular chemical or keep producing a particular chemical, and decisions by chemical company research and development departments as to whether a chemical substitute should be sought for a chemical with a TLV suggestive of suboptimal toxicity.

Despite the serious adverse consequences of an inaccurately determined TLV, the current TLV determination process is primarily dependent on an academic peer-reviewed literature in the midst of an irreproducibility crisis not yet fully explained or addressed.¹⁴ Also, a significant number of studies relied upon by ACGIH are not published and the data are not accessible to the public, thereby further exacerbating deficiencies in the TLV process. In addition, a well-established bias against the publication of negative results can additionally skew evaluations of the toxicological profile of a chemical toward overestimate of hazard.¹⁴ In this analysis, we evaluated the transparency and consistency of the data relied upon by ACGIH to set TLVs for 145 substances or groups of substances between the years 2008 and 2018.

Methods

Construction of Supplemental Table 1 on TLVs for chemicals adopted or reviewed from 2008 to 2018

To determine the chemicals for which TLVs have been established and the supporting documentation, it was necessary to purchase the 2018 edition of the 7th Edition, ACGIH TLVs and Biological Exposure Indices (BEIs^®).¹⁸ A search of the book/CD was conducted. On page 11, a section on adopted TLV values is presented in tabular form. The relevant table was analyzed, and the establishment dates of the adopted TLVs from 2008 to 2018 were recovered and placed into a table. Information on the 145 chemicals was then collected for the purpose of further examination. The information included the following: chemical name and Chemical Abstracts Service Registry Number(CASRN), TLV from ACGIH, year the TLV was adopted, human health basis for the TLV, references to sentinel studies used to form the recommendations for the TLV (as well as the range of dates for the sentinel articles), genotoxicity end points important in the TLVs, information on the nature of supporting data present in the documentation (raw data, statistically transformed retrievable data, statistically transformed data that were irretrievable, tabular data, graphical data, other data), and the page references for the information retrieved from the ACGIH 7th Ed. Documentation on each chemical.

All documentation for each chemical was reviewed thoroughly. Information in the TLV Recommendations was scrutinized, and all references used in the determination of the TLV were recorded. The TLV Basis was recorded. The section on genotoxicity studies was reviewed. Information from these sections of the documentation was placed in Table 1 for each of the 145 chemicals. The references were examined to determine the following: whether they were derived from peer-reviewed journals, irretrievability of URLs, findability of unpublished references, accessibility of the journals and books to the general public, relevance of the content of the reference or whether it was peripheral, and so on. The citations were all corrected (where necessary) and retyped into the uniform Vancouver style.

Table 1.

Distribution of different biological activities considered for the 145 chemicals.

TLV basis–critical effect^a	Percent
Irritation	30.4
CNS effects	12
Respiratory effects	8.8
Liver effects	8.7
Blood effects	6.4
Kidney effects	4.7
Skin effects	3.8
Cancer	3.7
Sensitization	2.8
All other effects	18.7

ACGIH: American Conference of Governmental and Industrial Hygienists.

^aMerkle SE: ACGIH’s Role in the Development of Exposure Assessment Guidelines for Occupational Hygiene. AIHA Carolinas Section, Spring Conference, Charlotte, NC, March 13–15, 2002. http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=2ahUKEwjn0bG3vfzdAhUQnFkKHWlCAvIQFjAAegQICRAC&url=http%3A%2F%2Fwww.aiha-carolinas.org%2Fmeeting-info%2Ftlvs.ppt&usg=AOvVaw3SknfQmKftcnD-zueeN74R

Construction of Supplemental Table 2 on carcinogenicity indices for top 145 chemicals reviewed and adopted by ACGIH between 2008 and 2018

Information on the carcinogenicity indices came from four sources: chemical name and CASRN, TLV, ACGIH Cancer Rating obtained from the 2018 edition of the 7th Edition, and ACGIH TLVs and BEIs.¹⁸ The National Toxicology Program (NTP) carcinogenicity rating was extracted from the NTP website (https://ntp.niehs.nih.gov/pubhealth/roc/index-1.html).¹⁹ The International Agency for Research on Cancer (IARC) carcinogenicity rating was taken from the IARC website (https://monographs.iarc.fr/agents-classified-by-the-iarc/)²⁰ The carcinogenicity index/ranking of the chemical was based on the process developed by Smith et al.²¹

Construction of Supplemental Table 3 on TLVs, economic value of the TLV-chemicals, and exposure information on the top 145 chemicals produced or imported during 2017

Information on the TLVs, economic value of the TLV-chemicals, and exposure information included the chemical name and CASRN and TLV value.¹⁸ The data on the pounds of each chemical produced or imported into the United States were obtained from 2017 data from the US EPA’s Chemical Data Reporting (CDR) database²² (http://www.epa.gov/chemical-data-reporting and http://epa.gov/cdr/).

Data on the costs per metric ton were obtained from Intratec at https://www.intratec.us/indexes-and-pricing-data/chemicals-pricing-data-store ²³ and http://www.icis.com/about/free-trials/ ²⁴ or were obtained from a search of the Internet. The estimated exposure data were taken from Labrèche et al. at http://www.irsst.qc.ca/media/documents/PubIRSST/R-895.pdf ²⁵ and anonymous https://submissions.swa.gov.au/SWAforms/wes/Documents/exposure-standards-discussion-paper.pdf.²⁶ The data for all other tables come from the 2018 edition of the 7th Edition, ACGIH TLVs and BEIs¹⁸ or searches of the Internet. All sources are noted at the bottom of each table.

Results

In total, ACGIH has issued approximately 657 chemical listings (i.e. TLVs), representing more than 700 chemicals.¹⁸ TLVs have been issued for a variety of situations including one unique organic chemical, one unique inorganic chemical, a chemical family (e.g. butanes or butenes), or an undefined group of chemicals, for example, soluble inorganic salts of beryllium. Since many of the chemical listings were issued many years ago, only the 145 chemicals for which TLVs were issued over the last 10 years (2008–2018) were analyzed as representative of current ACGIH practices (Table 1). Table 1 and references in Table 1 can be found in Online Supplemental Material.

Between the years 2008 and 2018, 145 chemical listings were adopted or reviewed. Figure 1 shows the number of chemical listings adopted or reviewed per year. On average, about 13 chemical listings were adopted or reviewed per year, ranging from 8 to 20 chemical listings per year.

Figure 1.

Frequency diagram of chemical TLVs adopted or reviewed from 2008 to 2018. TLV: threshold limit value.

As previously mentioned, the information in Table 1 includes the following: chemical name and CASRN, TLV from ACGIH, year the TLV was adopted, human health basis for the TLV, references to sentinel studies used to form the recommendations for the TLV (as well as the range of dates for the sentinel articles), genotoxicity end points important in the TLVs, information on the nature of supporting data present in the documentation (raw data, statistically transformed retrievable data, statistically transformed data that were irretrievable, tabular data, graphical data, other data), and the page references for the information retrieved from the ACGIH 7th Ed. Documentation on each chemical.

ACGIH considers a wide variety of biological end points for the human health basis for the TLV in setting the TLV. Table 1 shows the distribution of different biological activities considered for the 145 chemicals. The following potential toxicities and the percentage of chemicals considered for that end point in TLV setting are as follows: irritation (30.4%), Central Nervous System (CNS) effects (12%), respiratory effects (8.8%), liver effects (8.7%), blood effects (6.4%), kidney effects (4.7%), skin effects (3.8%), cancer (3.7%), sensitization (2.8%), and all other effects (18.7%).²⁷ Of the 145 chemicals (Table 1), only 38 (27%) relied upon a single toxicity end point in setting the TLV.

There were 1257 sentinel studies references by ACGIH for the 145 chemicals with TLVs adopted or reviewed from 2008 to 2018.¹⁸ The median publication date for these articles was 1988 ± 17 years. The earliest publication was 1919 and the latest was 2016 (Figure 2).

Figure 2.

Frequency diagram of references to sentinel studies per year for chemicals with TLVs adopted or reviewed from 2008 to 2018. TLV: threshold limit value.

Genotoxicity data were reported on most but not all of the 145 chemicals.¹⁸ About 8% (12 of 145) had no genotoxicity data. Typically, results for some combination of Ames assays, micronucleus assay, sister chromatid exchange chromosomal aberrations, mouse lymphoma assay, and/or dominant-lethal assay were provided. The most abundant information was on Ames test results. About 75% of all the chemicals were tested via the Ames assay. Of these 69% (75 of 108) were Ames negative, 17% (18 of 108) were Ames positive, and 14% (15 of 108) had equivocal Ames results.

For the 145 chemicals (Table 1), there was no case in which a single sentinel study could be identified as the sole basis for setting the TLV. Five of 145 (3.5%) chemical listings reported but a single reference, i.e. carfentrazone-ethyl, 1-chloro-1-nitropropane, methyl isopropyl ketone, silicon tetrahydride, and sulprofos. One chemical listing provided no references, that is, boron trifluoride. None of the 145 chemical listings reported the underlying methods employed for statistical analysis in the documentation related to determination of the TLV. None of the 145 chemical listings presented data in the supported documentation that could be used to facilitate outside independent statistical analysis.

As noted previously, 5 of the 145 (3.7%) chemicals in Table 1 incorporated rodent tumor (cancer end point) data into the determination of the TLV. In the limited number of cases dependent on cancer end points (Table 2), the chemical listing might not cite the relevant National Cancer Institute (NCI) study even when they exist, for example, vinyl acetate.^28
–30 When an NTP study is cited, for example, with vanadium pentoxide, the NTP report does contain tumor count data amenable to independent statistical analysis.³¹ However, that data are not in the ACGIH Documentation and independent statistical analysis of these few cases where “raw” NCI or NTP data are available would be superfluous as NCI and NTP data analyses are conducted by professional statisticians. Statistical analysis is not the basis upon which NCI or NTP studies are usually criticized.³² Table 2 can be found in the Supplemental Information.

Table 2.

Carcinogenicity indices from NTP, ACGIH, and IARC.

NTP, US Department of Health and Human Services	ACGIH	IARC
Group K: known to be human carcinogens	Group A1: confirmed human carcinogen	Group 1: carcinogenic to humans
Group R: reasonably anticipated to be human carcinogens	Group A2: suspected human carcinogen	Group 2A: probably carcinogenic to humans
	Group A3: confirmed animal carcinogen with unknown relevance to humans	Group 2B: possibly carcinogenic to humans
	Group A4: Not classifiable as a human carcinogen. “There are inadequate data on which to classify the agent in terms of its carcinogenicity in humans and/or animals.”	Group 3: The agent (mixture, exposure circumstance) is not classifiable as to its carcinogenicity to humans.
	Group A5: Not suspected as a human carcinogen.	Group 4: The agent (mixture, exposure circumstance) is probably not carcinogenic to humans

ACGIH: American Conference of Governmental and Industrial Hygienists; NTP: National Toxicology Program; IARC: International Agency for Research on Cancer.

Examination of Table 2 (carcinogenicity indices for top 145 chemicals reviewed and adopted by ACGIH between 2008 and 2018) shows that 128 of 145 chemical listings have either 3 or 4 entries notated as not otherwise specified (n.o.s.; as carcinogenic) or 1 or 2 entries notated as n.o.s. with entries for IARC, NTP, ACGIH, or Smith et al. carcinogenicity indices.²¹ In total, these 128 chemical listings show a high degree of consistency in terms of their carcinogenicity index rating. For example, a group R rating from NTP is analogous to a group A2 rating from ACGIH and a group 2A rating from IARC. A group A3 rating from ACGIH is analogous to a group 2B rating from IARC (Table 2).

The remaining 17 chemical listings in Table 2 are all considered to be more carcinogenic. Of these 17 chemical listings, 8 (47%) showed consistency across the recommending bodies in their carcinogenicity ratings. The carcinogenicity ratings on the remaining nine chemical listings were inconsistent with the ACGIH rating being less carcinogenic in all but a single case. Overall, 136 of the chemical listings (94%) showed consistency in their carcinogenicity indices.

Table 3 lists information on the TLV, cost and exposure information on the 145 chemicals possessing TLVs adopted or reviewed between 2008 and 2018 and produced or imported during 2017 (information on 2018 was not yet available). Table 3 can be found in the Supplemental Information, which lists the chemical name, TLV, pounds of chemical produced or imported annually in the United States (2017), average cost per pound of the chemical, metric tons of each chemical produced or imported, sales in US dollars (USD) per metric ton of chemical, and the estimated annual chemical exposure for males and females in all job categories in the United States. The information on TLVs was obtained from the 2018 7th Edition ACGIH Book of TLVs and BEIs.¹⁸ The data on the poundage of each chemical produced or imported into the United States were obtained from 2017 data from the US Environmental Protection Agency (EPA)’s CDR database²² (http://www.epa.gov/chemical-data-reporting and http://epa.gov/cdr/).

Data on the costs per metric ton were obtained from Intratec at https://www.intratec.us/indexes-and-pricing-data/chemicals-pricing-data-store ²³ and http://www.icis.com/about/free-trials/ ²⁴ or were obtained from a search of the Internet. The estimated exposure data were excerpted from Labrèche et al. at http://www.irsst.qc.ca/media/documents/PubIRSST/R-895 ²⁵ and anonymous https://submissions.swa.gov.au/SWAforms/wes/Documents/exposure-standards-discussion-paper.pdf.²⁶

The total sales of the 145 chemicals listed in Table 3 sum to USD$189,909,385,400. (It should be noted that metals and gases were not included. Some price and tonnage data were not available for certain chemicals.) The estimated sales for the total US chemical industry are approximately 800 billion USD. So, the chemical listings in Table 3 represent approximately 24% of the total sales of the US chemical industry.

Some degree of chemical exposure is common, although biologically significant chemical exposures are less common. Exposure to clinically significant levels of chemicals is more common in occupational settings than in the general population. As of October 2018, there are approximately 150,000,000 jobs in the United States, https://www.bls.gov.ces and https://www.deptofnumbers.com/employment/us/.³³ The US chemical industry directly employs over 800,000 workers with an additional 2,700,000 workers indirectly employed by industry suppliers.³⁴ The US chemical sector has more than 10,000 firms that produce over 70,000 different chemicals.³⁴ The 145 chemicals listed represent only a small fraction of the total number of chemicals produced or imported into the United States. It is extremely difficult to accurately estimate the percentage of the population exposed to a particular chemical, although estimates are calculated and published. For the 145 chemicals considered in this analysis, the percentage of the population estimated to be exposed to one or more of these 145 ranges from 0.1% and 33.0% or 150,000 to 49,500,000 people, respectively.^25,26,34

Discussion

Role of ACHIH within the regulatory framework

OSHA and the National Institute for Occupational Safety and Health (NIOSH) were created on December 29, 1970, when President Richard M. Nixon signed the Occupational Safety and Health Act.³⁵ The relative youth of OSHA and NIOSH can be contrasted with the formation of the predecessor of ACGIH in 1938.³⁶ In 1941, the TLV-CS Committee was established and became a standing committee in 1944. In 1946, ACGIH adopted the first list of 148 exposure limits, at that time termed maximum allowable concentrations (MACs). In 1956, the term MAC was changed to TLV. Currently, ACGIH provides TLVs for over 700 chemical substances and physical agents.^37,38 In January 2016, ACGIH became a 501(c)(3) charitable scientific organization and is not a regulatory agency of the United States or any other country. Therefore, from a legal perspective, ACGIH TLVs are nonbinding recommendations and not legally binding regulations.³⁹

The term “recommendation” belies the historical, regulatory, public health, and economic impact of the ACGIH TLV. The centrality of the role played by TLVs is due to the limited number of authoritative bodies in the United States, issuing similar exposure limits. OSHA issues legally binding PELs.^40,41 However, OSHA PELs are rarely updated and are not generally relied upon. In a January 2016 interview, then OSHA administrator David Michaels stated that

Many of these PELs are dangerously out of date and do not adequately protect workers. Past efforts to update our PELs have largely been unsuccessful. Since 1971, OSHA has successfully established or updated PELs for only about 30 chemicals. We have issued only one new exposure limit since the year 2000. As a result, many workers are currently being exposed to levels of chemicals that are legal, but not safe.⁴²

Due to OSHA’s lack of confidence in its own PELs, the agency developed an online resource, known as the Annotated Permissible Exposure Limits (or annotated PEL) tables (https://www.osha.gov/dsg/annotated-pels/index.html). The stated purpose of the Annotated PELs is “to enable employers to voluntarily adopt newer, more protective workplace exposure limits than those required by OSHA.” The Annotated PEL tables display a side-by-side comparison of OSHA PELs for general industry; NIOSH recommended exposure limits, California OSHA PELs, and ACGIH TLVs.⁴³ Therefore, the agency of the US Federal Government with primary responsibility for worker safety recommends that workplaces rely on the TLVs set by ACGIH.

Recommendations for improving the TLV-setting process

A thorough analysis covering the last 10 years and 145 substances or groups of substances demonstrates that the process by which ACGIH sets TLVs could be improved by increasing transparency. First, the purchase of an expensive book/CD is required to initiate the evaluation of the degree of transparency of the TLV process. Second, an independent outside third-party would not be able to evaluate the scientific logic and statistical analysis underpinning the promulgated TLVs. Third, the criteria for deciding the relative weighting of the diverse biological end points considered are not apparent. Compounding the already extremely problematic situation, many studies conducted over the last several years have demonstrated that a large but not exactly determinable percentage of the results in the peer-reviewed academic literature are not reproducible in another laboratory attempting to employ the original protocol.¹⁴ Based on analyses conducted in different fields of study, a reasonable estimate would be that about 40–50% of the biomedical literature is not replicable.^{14,44

–48} ACGIH states that the primary resource upon which it relies in setting TLVs is this same body of peer-reviewed academic literature in the midst of a replicability crisis. Given the enormous number of workers whose safety is affected by the TLV process (Table 3), and the hundreds of billions of dollars of commerce involved (Table 3), the opaqueness of the current TLV setting process should be replaced by a protocol that describes the selection of studies, numerical values extracted for consideration, statistical methods employed, actual statistical calculations, raw data analyzed, and logic employed. Implementation of these suggested changes would represent a modernization of protocol but would not require outlay of additional resources. Hopefully, ACGIH, industry, and government can collaborate in improving the workplace air standard setting process.

Many online open-access journals now accept supplemental materials that can be accessed by interested readers. Going forward, ACGIH might consider a similar online repository for the voluminous raw data underlying sentinel studies. The raw data would need to be provided by the authors of the sentinel study, preferably as part of the original publication. Since many older studies that are relevant to the TLV-setting process were published prior to the implementation of supplemental materials, ACGIH could improve transparency by explicitly elucidating the transformed data values and their location in the specific publications upon which the TLVs are derived. If the authors of a sentinel study are in possession of archived raw data, these authors should be willing to share these data for the purpose of independent outside statistical analysis. Results from independent statistical analysis would be shared with all interested parties for the purpose of improving the quality of information available to the ACGIH expert panelists. In summary, the emphasis in TLV setting would shift from peer-reviewed studies to transparent peer-reviewed studies and Good Laboratory Practices (GLP) reports facilitating commentary by all interested parties. A transparent, more science-based approach to TLV-setting with worker safety as the paramount goal would serve as an important adjunct to the efforts of both national and international regulatory agencies.

Perspective

The mission to promote health and safety in the workplace undertaken by volunteer industrial hygienists and other occupational and safety professionals over many years under the auspices of ACGIH is highly laudable. ACGIH’s TLVs and BEIs are not and have never been meant to be consensus standards.⁴⁹ TLVs and BEIs are health-based values intended for use in the practice of industrial hygiene as guidelines or recommendations to assist in the control of potential workplace hazards.^49,50 TLVs and BEIs are only one of multiple factors to be considered in evaluating specific workplace situations and conditions.⁵⁰

Under the auspices of ACGIH, the work of multidisciplinary committees that review and analyze published and peer-reviewed literature across various scientific disciplines including industrial hygiene, toxicology, occupational medicine, and epidemiology represents valuable and unique expressions of science-based biomedical opinion.⁵¹ Numerous benefits emanate from such voluntary cooperation among scientists and clinicians including joint hypothesis generation, discovery of synergistic observations, collaborative insights regarding risk characterization, elucidation of possible mechanisms and risk modifiers, and open discussions on impact of antecedent or intervening variables. Collective innovative thinking has historically resulted in better and more productive solutions to challenging issues.^52,53

It is not our intent to, in the words of Murray Kempton, to play the role of critic of this integral system by entering the battlefield to shoot the wounded after the war but rather to address and potentially correct shortfalls in the process.^7,54,55 ACGIH did not set out to have OSHA become dependent on the TLV process but rather the dependency developed due to problems experienced by OSHA with its own PEL system.⁵⁶ The planned updates and improvements in the OSHA PEL system should hopefully alleviate some of the over reliance on ACGIH TLVs and BEIs.⁵⁷

Supplemental Material

Supplemental Material, Supplemental_1_References_for_145_TLVs_Alphabetical_Order - 142 ACGIH Threshold Limit Values^® (TLV^®s) established from 2008-2018 lack consistency and transparency

Supplemental Material, Supplemental_1_References_for_145_TLVs_Alphabetical_Order for 142 ACGIH Threshold Limit Values^® (TLV^®s) established from 2008-2018 lack consistency and transparency by Carr J Smith, and Thomas A Perfetti in Toxicology Research and Application

Supplemental Material

Supplementary_Tables - 142 ACGIH Threshold Limit Values^® (TLV^®s) established from 2008-2018 lack consistency and transparency

Supplementary_Tables for 142 ACGIH Threshold Limit Values^® (TLV^®s) established from 2008-2018 lack consistency and transparency by Carr J Smith, and Thomas A Perfetti in Toxicology Research and Application

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Carr J Smith

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Supplementary Material

Please find the following supplemental material available below.

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For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

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142 ACGIH Threshold Limit Values ® (TLV ® s) established from 2008-2018 lack consistency and transparency

Abstract

Keywords

Background

Introduction

Methods

Construction of Supplemental Table 1 on TLVs for chemicals adopted or reviewed from 2008 to 2018

Construction of Supplemental Table 2 on carcinogenicity indices for top 145 chemicals reviewed and adopted by ACGIH between 2008 and 2018

Construction of Supplemental Table 3 on TLVs, economic value of the TLV-chemicals, and exposure information on the top 145 chemicals produced or imported during 2017

Results

Discussion

Role of ACHIH within the regulatory framework

Recommendations for improving the TLV-setting process

Perspective

Supplemental Material

Supplemental Material, Supplemental_1_References_for_145_TLVs_Alphabetical_Order - 142 ACGIH Threshold Limit Values® (TLV®s) established from 2008-2018 lack consistency and transparency

Supplemental Material

Supplementary_Tables - 142 ACGIH Threshold Limit Values® (TLV®s) established from 2008-2018 lack consistency and transparency

Footnotes

Declaration of conflicting interests

Funding

ORCID iD

References

Supplementary Material

Supplemental Material, Supplemental_1_References_for_145_TLVs_Alphabetical_Order - 142 ACGIH Threshold Limit Values^® (TLV^®s) established from 2008-2018 lack consistency and transparency

Supplementary_Tables - 142 ACGIH Threshold Limit Values^® (TLV^®s) established from 2008-2018 lack consistency and transparency