16 research outputs found
Inter-laboratory comparison of water solubility methods applied to difficult-to-test substances
Water solubility is perhaps the single most important physical–chemical property determining the environmental fate and effects of organic compounds. Its determination is particularly challenging for compounds with extremely low solubility, frequently referred to as “difficult-to-test” substances and having solubility’s generally less than 0.1 mg/L. The existing regulatory water solubility test for these compounds is the column elution method. Its applicability, however, is limited, to non-volatile solid or crystalline hydrophobic organic compounds. There currently exists no test guideline for measuring the water solubility of very hydrophobic liquid, and potentially volatile, difficult-to-test compounds. This paper describes a “slow-stir” water solubility methodology along with results of a ring trial across five laboratories evaluating the method’s performance. The slow-stir method was applied to n-hexylcyclohexane, a volatile, liquid hydrophobic hydrocarbon. In order to benchmark the inter-laboratory variability associated with the proposed slow-stir method, the five laboratories separately determined the solubility of dodecahydrotriphenylene, a hydrophobic solid compound using the existing column elution guideline. Results across the participating laboratories indicated comparable reproducibility with relative standard deviations (RSD) of 20% or less reported for each test compound – solubility method pair. The inter-laboratory RSD was 16% for n-hexylcyclohexane (mean 14 µg/L, n = 5) using the slow-stir method. For dodecahydrotriphenylene, the inter-laboratory RSD was 20% (mean 2.6 µg/L, n = 4) using the existing column elution method. This study outlines approaches that should be followed and the experimental parameters that have been deemed important for an expanded ring trial of the slow-stir water solubility method. [Figure not available: see fulltext.].</p
Assessing Aromatic-Hydrocarbon Toxicity to Fish Early Life Stages Using Passive-Dosing Methods and Target-Lipid and Chemical-Activity Models
Aromatic hydrocarbons (AH) are known
to impair fish early life
stages (ELS). However, poorly defined exposures often confound ELS-test
interpretation. Passive dosing (PD) overcomes these challenges by
delivering consistent, controlled exposures. The objectives of this
study were to apply PD to obtain 5 d acute embryo lethality and developmental
data
and 30 d chronic embryo–larval survival and growth-effects
data using zebrafish with different AHs; to analyze study and literature
toxicity data using target-lipid (TLM) and chemical-activity (CA)
models; and to extend PD to a mixture and test the assumption of AH
additivity. PD maintained targeted exposures over a concentration
range of 6 orders of magnitude. AH toxicity increased with log <i>K</i><sub>ow</sub> up to pyrene (5.2). Pericardial edema was
the most sensitive sublethal effect that often preceded embryo mortality,
although some AHs did not produce developmental effects at concentrations
causing mortality. Cumulative embryo–larval mortality was more
sensitive than larval growth, with acute-to-chronic ratios of <10.
More-hydrophobic AHs did not exhibit toxicity at aqueous saturation.
The relationship and utility of the TLM–CA models for characterizing
fish ELS toxicity is discussed. Application of these models indicated
that concentration addition provided a conservative basis for predicting
ELS effects for the mixture investigated
In Vivo Biotransformation Rates of Organic Chemicals in Fish: Relationship with Bioconcentration and Biomagnification Factors
In
vivo dietary bioaccumulation experiments for 85 hydrophobic
organic substances were conducted to derive the in vivo gastrointestinal
biotransformation rates, somatic biotransformation rates, bioconcentration
factors (BCF), and biomagnification factors (BMF) for improving methods
for bioaccumulation assessment and to develop an in vivo biotransformation
rate database for QSAR development and in vitro to in vivo biotransformation
rate extrapolation. The capacity of chemicals to be biotransformed
in fish was found to be highly dependent on the route of exposure.
Somatic biotransformation was the dominant pathway for most chemicals
absorbed via the respiratory route. Intestinal biotransformation was
the dominant metabolic pathway for most chemicals absorbed via the
diet. For substances not biotransformed or transformed exclusively
in the body of the fish, the BCF and BMF appeared to be closely correlated.
For substances subject to intestinal biotransformation, the same correlation
did not apply. We conclude that intestinal biotransformation and bioavailability
in water can modulate the relationship between the BCF and BMF. This
study also supports a fairly simple rule of thumb that may be useful
in the interpretation of dietary bioaccumulation tests; i.e., chemicals
with a BMF<sub>L</sub> of <1 tend to exhibit BCFs based on either
the freely dissolved (BCF<sub>WW,fd</sub>) or the total concentration
(BCF<sub>WW,t</sub>) of the chemical in the water that is less than
5000