Characterizing the Narcotic Effects of Acute Nonpolar Solvent Exposure by Quantitative Comparison of Reaction Time Data to Alcohol-Intoxicated Subjects in Human Studies

Details

• Personal Author:
  Frank EA ; Smith RJ
• Description:
  Background and Purpose: NIOSH develops Immediately Dangerous to Life or Health (IDLH) values to protect workers from serious injury or death in the event of unforeseen exposures to high concentrations of chemical gases such as during an accidental release or spill. IDLH values are used in combination with direct monitoring and are designed to enable workers to evacuate a workplace without experiencing irreversible or potentially lethal health effects, including incapacitating effects that could impair a worker's ability to escape further exposure. Experimental data from studies in human volunteers can be used to measure the narcotic effects of exposure to nonpolar solvents such as toluene, but there are no well-accepted definitions or standards for what constitutes an incapacitating effect level for the purposes of determining an IDLH value or any other kind of short-term toxicity estimate. Methods: This work evaluated the feasibility of characterizing changes in simple reaction time (SRT) test performances in human volunteers acutely exposed to toluene by way of quantitative comparison to the effect magnitudes observed in human subjects administered similar SRT tests under the influence of alcohol as measured by blood alcohol content (BAC). Datasets were identified from literature that reported SRT performance in both toluene-exposed and alcohol-administered subjects in sufficient detail to compare the effect sizes across datasets. These data were used to quantitatively estimate the concentration of toluene in acute exposures causing a degradation on SRT performance equivalent to a known BAC. Two key studies exposed groups of 12 adults to 100, 300, 500, or 700 ppm toluene for 20-minute periods, while 40 adults were tested at measured BACs of 0.02, 0.035, 0.05, or 0.08%. The relative impact of intoxication on SRT performance was expressed in terms of the ratio of group mean change in SRT in the intoxicated subjects compared to SRT performance of unexposed controls. Ordinary least squares were used to fit linear dose-response functions to the group mean SRT ratios for intoxicated:control subjects and estimates of the toluene concentration associated with impaired SRT performance equivalent to a given BAC were derived by multiplying the BAC by the alcohol:toluene ratio of the fitted slopes. Precision of estimation of the toluene concentration was based on 95% confidence limits for the ratio of the slopes. Results: Group mean performance degradations in SRT tests in toluene- or alcohol-intoxicated groups were fitted to ordinary-least-squares functions, yielding central estimates of toluene concentrations corresponding to performance at a given BAC along with the confidence limits of the comparisons. The effects of 0.03, 0.05, or 0.08% BAC were functionally equivalent to exposure to 300, 500, and 810 ppm toluene with exposure durations of 20 minutes. The lower-bound 95% confidence limits were 170, 290, and 460 ppm, respectively. The risk of error from bias due to differences in representation of group means (arithmetic vs geometric averaging) ranged from 0.1 to 0.5%, appearing negligible. Conclusions: Data related to acute neurological impairment and narcosis in alcohol-intoxicated adult subjects may be used to characterize the effect of acute exposure to nonpolar solvents such as toluene. This provides a context for determining when changes in experimental endpoints signify a level of impairment that would affect a worker's ability to escape from a hazardous workplace during an emergency. This approach leverages the considerable body of quantitative data on the acute neurobehavioral effects of alcohol in adults to characterize the concentration-effect relationship of nonpolar solvent exposure in terms of risk policy and provides a recognizable standard for consideration of functional impacts in workers. [Description provided by NIOSH]
• Subjects:
  Hazardous Substances Occupational Health Safety Solvents Toluene
• Keywords:
  Chemical Hazards Dose Response Gases IDLH Immediately Dangerous To Life Or Health Intoxication
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Ohio ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  DSI - Division of Science Integration
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  198
• NIOSHTIC Number:
  nn:20069331
• Citation:
  Toxicologist 2024 Mar; 198(S1):300
• CAS Registry Number:
  Toluene (CAS RN 108-88-3)
• Federal Fiscal Year:
  2024
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 63rd Annual Meeting & ToxExpo, March 10-14, 2024, Salt Lake City, Utah
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:85aef8e32f518e1d6e8d66653e280f6e4a299e8011e84ac87cd7ad2ae389342f1b61c50e70666691f5985fb3a061f1a8cb66806c1525334fe6721181556cdfc2
• Download URL:
  https://stacks.cdc.gov/view/cdc/207831/cdc_207831_DS1.pdf
• File Type:
  [PDF - 521.67 KB ]