Hazard is a curve, not a label.

6.1 Hazard and risk

Hazard is a substance’s intrinsic capacity to cause harm; risk combines hazard with exposure. Design can lower both: choose ions with lower intrinsic toxicity, and design processes that recover the solvent so little reaches people or water. The founder’s 2016 study found that, for five common ionic liquids and under its release assumptions, modeled freshwater ecotoxicity from making the liquid was nearly an order of magnitude larger than from its release during use. Precursor and route choices can therefore matter as much as the ion itself.

6.2 Dose–response

Concentration–effect data are commonly described by a log-logistic (Hill) curve. The effect at concentration c rises from 0 to E_max:

h: slope (Hill coefficient); EC_x: concentration giving x% effect. A steep curve means EC₁₀ is close to EC₅₀; a shallow one means effects start far below it.

6.3 From acute tests to chronic values

Many endpoints are short-term (acute) EC₅₀ or LC₅₀ values, while life-cycle characterization needs chronic values. In the founder’s 2016 USEtox study, acute data were converted to chronic with an acute-to-chronic ratio of 2 (following USEtox guidance), and no-observed-effect concentrations were extrapolated to EC₅₀ by a factor of 9. Such factors are conventions; they carry uncertainty that should travel with the result.

6.4 Species sensitivity distributions

Species differ in sensitivity. A species sensitivity distribution (SSD) treats the chronic EC₅₀ values of tested species as a sample from a log-normal distribution:

μ, s: mean and standard deviation of log₁₀ EC₅₀ across species; z_p: standard normal quantile (z_0.05 = −1.645). HC₅₀ is the geometric mean; HC₅ is the concentration at which 5% of species are exposed above their chronic EC₅₀.

USEtox builds its freshwater effect factor from the HC₅₀, and the characterization factor from fate, exposure and effect (USEtox 1.01 manual):

6.5 Persistence and bioaccumulation: a PBT screen

Under REACH Annex XIII, a substance is PBT if it meets all three criteria. Persistent: degradation half-life above 60 days in marine water, 40 days in fresh or estuarine water, 180 days in marine sediment, or 120 days in fresh or estuarine water sediment or in soil. Bioaccumulative: bioconcentration factor (BCF) above 2,000. Toxic: long-term NOEC or EC₁₀ below 0.01 mg L⁻¹ for aquatic organisms, or classification as carcinogenic, mutagenic or toxic for reproduction (categories 1A/1B; reproductive category 2 also counts), or specific target organ toxicity after repeated exposure (STOT RE 1 or 2). Very persistent (vP) and very bioaccumulative (vB) use stricter values (half-life above 60 days in water and 180 days in sediment or soil; BCF above 5,000).

Since 2023 the EU CLP Regulation also has hazard classes for persistent, mobile and toxic (PMT) and very persistent, very mobile (vPvM) substances, which matter for water-soluble ions. Mobility is judged from the organic carbon–water partition coefficient: M if log K_oc < 3, vM if log K_oc < 2. The 2016 paper’s K_oc values (log K_oc 2.15–2.60) meet M but not vM for all five liquids; a PMT conclusion would also need the P and T criteria.

Half-life t_½ = ln 2 / k from the paper’s first-order biodegradation rates in water; the paper assigned 1 × 10⁻²⁰ s⁻¹ (effectively no degradation) to liquids it classed as nonbiodegradable. The persistence entries marked “potentially P” are liquids with less than 1% degradation in 28 days, a failed screening test rather than a measured half-life. The bioaccumulation column uses the paper’s fish bioaccumulation factors, estimated from K_ow, as a stand-in for BCF; K_ow-based regressions were developed for neutral organics and are not validated for ions. The toxicity column compares the lowest chronic EC₅₀ with 0.01 mg L⁻¹, which is indicative only, because the criterion is defined on NOEC or EC₁₀. A screen on model inputs is not a regulatory assessment.

6.6 Flammability

Under the OSHA Hazard Communication Standard (Appendix B.6), a flammable liquid has a flash point at or below 93 °C, in four categories:

Negligible vapor pressure makes most ionic liquids hard to ignite as liquids, but it does not make them non-combustible. Smiglak and co-workers (2006) reported that while many ionic liquids are not flammable themselves, a large group, including commercial ones, are combustible, owing to positive heats of formation, oxygen content and decomposition products. Flammability is therefore a criterion to test, not to assume (Chapter 5, Eq. 5.6).

6.7 Human health: from cells to dose

Human-health assessment runs from computational alerts, through in vitro assays (including human cell lines), to in vivo studies where regulation requires them; the OECD test guidelines for each tier are listed in Methods 06. In vitro potency becomes a human dose through in vitro–in vivo extrapolation (IVIVE) and physiologically based pharmacokinetic (PBPK) models, whose equations are given there. Carcinogenicity classifications (IARC groups) apply to precursors and by-products as well as to the product.