Combined Toxic Effects of Chemicals

cumulativeBelow is a summary of some of the very similar methods and rationale used by agencies to assess the combined toxic effects of chemicals.

ACGIH
Source: TLV’s and BEI’s Publication

  • Recommends an additive (combined) approach for two or more substances that affect the same target organ/system
  • The ratio of the exposure concentrations are summed together
  • {C_1}/{t_1} + {C_2}/{t_2} + cdots {C_n}/{t_n}

    where: C = observed concentration, t = TLV

  • If the sum exceeds one, the TLV for the mixture is considered to have been exceeded
  • Additive formula applies to simultaneous exposures for hazardous substances with TWA’s, STEL’s, Excursion Limits, and/or Ceiling Limits. Bases (TWA’s, STEL’s, etc.) should be kept consistent, as feasible
  • Exceptions are made when it is believed the major effects of the chemicals are not additive or possibly when the mixtures contain carcinogens
  • Synergistic effects should be carefully considered

OSHA
Source: 29 CFR 1910.1000

  • Recommends an additive (combined) approach for two or more substances that affect the same target organ/system
  • The ratio of the exposure concentrations are summed together
  • {C_1}/{t_1} + {C_2}/{t_2} + cdots {C_n}/{t_n}

    where: C = observed concentration, t = TLV

  • If the sum exceeds one, the TLV for the mixture is considered to have been exceeded
  • Approaches to chemicals with similar effects are not restricted

NIOSH
Source: NIOSH Methylene Chloride Intelligence Bulletin

  • Recommends an additive (combined) approach for two or more substances that affect the same target organ/system
  • The ratio of the exposure concentrations are summed together
  • {C_1}/{t_1} + {C_2}/{t_2} + cdots {C_n}/{t_n}

    where: C = observed concentration, t = TLV

  • If the sum exceeds one, the TLV for the mixture is considered to have been exceeded
  • Specifically addressed methylene chloride in the presence of carbon monoxide due to the formation of carboxyhemoglobin

Other Agencies

    ATSDR

  • Typically a semi-quantitative screening process using flow-chart methodology
  • Useful:
    1. when exposures to the components are not clearly hazardous when considered singly, but potentially
      hazardous due to additivity or interactions when considered together
    2. when the community-specific health outcome data indicated that the site might have an adverse
      impact on human health, but the exposure-based assessment of each separate component did not
    3. when the health outcome data were ambiguous or did not indicate an adverse impact on human
      health, but the exposure-based assessment identified a potential hazard from one or more of the
      components.

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