Carr J Smith, PhD, DABT

Albemarle Corporation

Thomas A Perfetti, PhD

Perfetti & Perfetti LLC

Improving the ACGIH TLV Process

April 2019

Primary Source for ACGIH Threshold Limit Values (TLVs)

ACGIH states that “…the TLV®-CS Committee preferably relies on published, peer reviewed literature available in the public domain.”

Peer-Reviewed Literature – Replication CrisisIn 2012, Begley and Ellis reported that scientists at Amgen had attempted to confirm published findings related to research topics of possible interest to Amgen. Fifty-three preclinical cancer papers were deemed “landmark” studies. The authors were “shocked” when scientific findings were confirmed in only 6 (11%) cases.

Replication Crisis is of Unknown MagnitudeSince Bagley and Ellis (2012), a number of studies have been conducted by other researchers demonstrating an inability to replicate experiments published in the peer-reviewed literature in a variety of other fields, e.g., experimental psychology.

Basis of Peer-Reviewed Literature Replication Crisis• Primary causes underlying the replication crisis

likely to be different across different experimental disciplines.

• Percentage of studies that are not replicable probably varies by field of study.

• Extremely expensive and time-consuming to attempt to replicate already published experiments.

• Not feasible for many studies conducted on humans or large animal studies.

Factors Possibly Related to Poor Replication

• Risk factors include: Confirmation bias wherein researchers unconsciously work

backwards from the desired result. Throwing out data outliers without proper statistical

justification regressing results back toward the desired result. Improper selection of statistical tests. Publishing either a single run or a double run of an

experimental result rather than conducting experiments in triplicate.

Proliferation of journals diluting the peer-reviewer talent pool

Publication Bias Compounds Irreproducibility Crisis

• Compounding the irreproducibility crisis is the existence of a significant bias against the publication of negative results. In the toxicology setting, negative toxicity test results are infrequently published as compared with reports that a chemical possesses a particular toxicity in a given test.

Data Transparency is Essential

• Error rate in peer-reviewed literature is of unknown magnitude but has been significant whenever examined.

• Not feasible for third parties to repeat experiments.• Providing the raw, not statistically transformed data,

underlying the results of studies used to set TLVs would facilitate independent statistical analysis.

TLVs Lack Data Transparency

Academic studies upon which ACGIH relies to determine TLVs rarely report raw data not already statistically transformed. The raw data cannot be back calculated.

Large Survey of TLVs Demonstrates Data Insufficiency

• From 2008-2018, 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 145 TLVs® showed sufficient data to independently substantiate ACGIH’s® evaluations.

Most Relevant Studies Underlying a TLV Usually Cannot be Identified

• In the majority of cases sentinel studies upon which calculation of the TLV® was based cannot be determined.

ACGIH TLVs Are Used by US Federal Government

• OSHA recommends workplaces rely on ACGIH® TLVs® and NIOSH RELs rather than older OSHA PEL values to optimize worker safety.

Adverse Impact of Inaccurate TLVs

• Inaccurate or poorly substantiated determination of TLVs® can adversely impact both human health and commerce, as net US sales of the 145 substances represents an estimated $189 billion, about one-fourth of the $800 billion chemical market in the US.

Needed Changes to ACGIH TLV Process

• ACGIH® should provide the studies relied upon, individual data values supporting the TLVs®, and statistical calculation methods underlying the development of a TLV®.

Inaccurate TLVs Spread Nationally and Internationally

• 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.

EPA Reforms Regarding Data Transparency

• Increased transparency by ACGIH® is consistent with recent reforms implemented by US EPA.

References

• Smith, C. J., & Perfetti, T. A. (2018). Improving the ACGIH threshold limit value (TLV®) process. Toxicology Research and Application. https://doi.org/10.1177/2397847318801758

• Smith, C.J., & Perfetti, T.A. (2019). 142 ACGIH® Threshold Limit Values® (TLVs®) Established from 2008-2018 Lack Consistency and Transparency. Toxicology Research and Application. https://doi.org/10.1177/2397847318822137

https://doi.org/10.1177/2397847318801758https://doi.org/10.1177/2397847318822137

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