Daniel J. Call

QSARs for photoinduced toxicity: I. Acute lethality of polycyclic aromatic hydrocarbons to Daphnia magna

Research with a variety of aquatic species has shown that while polycyclic aromatic hydrocarbons (PAHs) are generally not acutely toxic in conventional laboratory tests, many are extremely toxic in the presence of sunlight. In an effort to develop a model for predicting which PAHs may exhibit photo-induced toxicity, Newsted and Giesy (1987) reported a parabolic relationship between the toxicity and the energy of the triplet state of a variety of PAHs. We have reexamined these data and propose a more mechanistic explanation for the prediction of photo-induced PAH toxicity. Photo-induced toxicity is the result of competing processes such as stability and light absorbance which interact to produce a complex, multilinear relationship between toxicity and chemical structure. We sought a molecular descriptor which could be computed from structure rather than measured empirically. We found that a measure of the energy stabilization of the toxicant in the form of the HOMO-LUMO (Highest Occupied Molecular Orbital - Lowest Unoccupied Molecular Orbital) gap provided a useful index to explain the persistence, light absorption, and photo-induced toxicity of PAHs. The model clearly shows, for example, why phenanthrene and tetracene are not toxic while anthracene is highly phototoxic. Those PAHs exhibiting photo-induced toxicity were consistently within HOMO-LUMO gap “window” of 7.2 ± 0.4 eV.

A QSAR analysis of substituent effects on the photoinduced acute toxicity of PAHs

Photoinduced toxicity of polycyclic aromatic hydrocarbons (PAHs) is a result of competing effects including stability and light absorbance of the molecules as well as irradiation parameters. The energy difference between the Highest Occupied Molecular Orbital and the Lowest Unoccupied Molecular Orbital (HOMO-LUMO gap), which can be computed directly from structure, was found to be the molecular descriptor that best distinguishes phototoxic chemicals from non-phototoxic chemicals. Aromatic chemicals that are phototoxic in sunlight have HOMO-LUMO gap energies that fall in the range of 6.7 to 7.5 eV. This study showed that the effect of most substituents on the HOMO-LUMO gap was negligible, and that phototoxicity in an aromatic chemical is likely only if the parent aromatic structure is phototoxic. Exceptions included substituents that add to delocalization (nitro and alkenyl) which could shift some chemicals with a HOMO-LUMO gap just above 7.5 eV into the domain of photoinduced toxicity.

Integrated assessment of contaminated sediments in the lower Fox River and Green Bay, Wisconsin.

Samples of sediment and biota were collected from sites in the lower Fox River and southern Green Bay to determine existing or potential impacts of sediment-associated contaminants on different ecosystem components of this Great Lakes area of concern. Evaluation of benthos revealed a relatively depauperate community, particularly at the lower Fox River sites. Sediment pore water and bulk sediments from several lower Fox River sites were toxic to a number of test species including Pimephales promelas, Ceriodaphnia dubia, Hexagenia limbata, Selenastrum capricornutum, and Photobacterium phosphorum. An important component of the observed toxicity appeared to be due to ammonia. Evaluation of three bullhead (Ictalurus) species from the lower Fox River revealed an absence of preneoplastic or neoplastic liver lesions, and the Salmonella typhimurium bioassay indicated relatively little mutagenicity in sediment extracts. Apparent adverse reproductive effects were noted in two species of birds nesting along the lower Fox River and on a confined disposal facility for sediments near the mouth of the river, and there were measurable concentrations of potentially toxic 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), and planar polychlorinated biphenyls (PCBs) both in the birds and in sediments from several of the study sites. Based on toxic equivalency factors and the results of an in vitro bioassay with H4IIE rat hepatoma cells, it appeared that the majority of potential toxicity of the PCB/PCDF/PCDD mixture in biota from the lower Fox River/Green Bay system was due to the planar PCBs. The results of these studies are discussed in terms of an integrated assessment focused on providing data for remedial action planning.

Effects of Chironomus tentans larval growth retardation on adult emergence and ovipositing success: implications for interpreting freshwater sediment bioassays

A laboratory study was conducted with Chironomus tentans to assess the significance of growth retardation of third-to fourth-instar larvae over a 10-d test period on long-term survival, adult emergence, and ovipositing success. Data were intended to provide interpretive guidance for the commonly used growth endpoint in 10-d sediment bioassays with C. tentans. Larval growth was controlled by using six feeding levels ranging from 0.2 to 5.9 mg dry weight Tetrafin® fish food per day. Mean 10-d survival was ≥88% at all feeding levels, but larval growth decreased significantly (p<0.05) with each decrease in feeding level. Cumulative successful emergence of adult C. tentans decreased significantly with decreasing larval growth. Mean times to emergence always increased with decreasing growth rates and effects were generally more pronounced for females than males. At the lowest 10-d mean growth where successful emergence occurred (0.27 mg), the times to emergence doubled relative to the times observed at the highest 10-d mean growth (1.03 mg). Ten-day larval growth retardation was strongly correlated with reduction in adult emergence success (r2 = 0.96). Growth retardations ≥64% resulted in 86–100% reductions in adult emergence. Growth retardation in the range of 35 to 50% equated with comparable percent reductions in adult emergence success. Although fewer females successfully emerged at 10-d growths of 0.37 and 0.74 mg relative to the highest 10-d growth (1.03 mg), ovipositing success of these females did not appear to be adversely affected by either their slower growth rates or their lower mean dry weights (0.62 and 0.99 mg, respectively). Growth of second generation larvae did not appear to be affected by maternal growth rate, but rather appeared to be solely correlated with their own feeding level.

An assessment of the toxicity of phthalate esters to freshwater benthos. 2. Sediment exposures

Tests were performed with the freshwater invertebrates Hyalella azteca, Chironomus tentans, and Lumbriculus variegatus to determine the acute toxicity of six phthalate esters, including dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP), butylbenzyl phthalate (BBP), di-n-hexyl phthalate (DHP), and di-2-ethylhexyl phthalate (DEHP). It was possible to derive 10-d LC50 (lethal concentration for 50% of the population) values only for the four lower molecular weight esters (DMP, DEP, DBP, and BBP), for which toxicity increased with increasing octanol-water partition coefficient (Kow) and decreasing water solubility. The LC50 values for DMP, DEP, DBP, and BBP were 28.1, 4.21, 0.63, and 0.46 mg/L for H. azteca; 68.2, 31.0, 2.64, and > 1.76 mg/L for C. tentans; and 246, 102, 2.48, and 1.23 mg/L for L. variegatus, respectively. No significant survival reductions were observed when the three species were exposed to either DHP or DEHP at concentrations approximating their water solubilities.

Bromacil and diuron herbicides: toxicity, uptake, and elimination in freshwater fish.

Fathead minnows, 30 days old, were exposed to technical grade bromacil and diuron in flow-through tests to determine acute toxicity. LC50 values for bromacil were 185, 183, 182 and 167 mg/L at 24, 48, 96, and 168 hr, respectively; and for diuron, 23.3, 19.9, 14.2, and 7.7 mg/L at 24, 48, 96, and 192 hr, respectively. Eggs, newly hatched fry, and juvenile fish were continuously exposed to lower concentrations of the herbicides for 64 days. Growth was significantly reduced (p ⩽ 0.01) at the lowest bromacil exposure of 1.0 mg/L. Therefore, it was not possible to determine a “no effect” concentration. The “no effect” concentration for diuron was 33.4 μg/L, while the lowest concentration which resulted in adverse effects was 78.0 μg/L. Adverse effects at 78.0 μg/L were an increased incidence of abnormal or dead fry immediately after hatch (p ⩽ 0.01) and decreased survival throughout the exposure period (p ⩽ 0.05). Neither herbicide accumulated significantly in fish tissue, as bioconcentration factors were <3.2 and 2.0 for bromacil and diuron, respectively. Rainbow trout (Salmo gairdneri) injected with radiolabeled bromacil or diuron eliminated over 90% of the radioactivity within 24 hr. Parent compound and metabolites were detected in the aquarium water in both cases. Metabolites of diuron recovered from the water included 3,4-dichloroaniline and several demethylated products.

Uptake, elimination, and metabolism of three phenols by fathead minnows

Uptake rates of total14C in fathead minnows (Pimephales promelas) exposed to sublethal concentrations of radiolabeled test compounds followed the order: phenol > 2,4,5-trichlorophenol >p-nitrophenol. Mean whole body14C concentration factors were 15,800, 1,850, and 180 for phenol, 2,4,5-trichlorophenol, andp-nitrophenol exposures, respectively. Only minor amounts of tissue14C was parent compound after 28 days of exposure in fish exposed to phenol andp-nitrophenol, while 78.6% of the14C was parent compound in 2,4,5-trichlorophenol exposed fish. Tissue14C in fish exposed to 2,4,5-trichlorophenol was eliminated at a faster rate than in fish exposed to phenol orp-nitrophenol. Observed mean14C depuration half-lives for lower and higher exposures combined were 387, 150, and 12 hours for phenol,p-nitrophenol, and 2,4,5-trichlorophenol, respectively. Parent compound comprised 1.5, 2.7, and 0.7% of total14C for phenol, 2,4,5-trichlorophenol, andp-nitrophenol, respectively, after 28 days of depuration.The percentage of acetone-unextractable14C increased from the end of uptake to the end of depuration for phenol and 2,4,5-trichlorophenol, and decreased slightly forp-nitrophenol.14C contribution from polar metabolites increased relative to total14C during the depuration phase for 2,4,5-trichlorophenol andp-nitrophenol.

Acute toxicity of silver to selected fish and invertebrates

The toxicity of silver to aquatic organisms is examined. The following organisms were exposed to silver nitrate in acute toxicity tests: flagfish (Jordanella floridae), fathead minnows (Pimephales promelas), scuds (Gammarus pseudolimnaeus), and parthenogenetic midges (Tanytarsus dissimilis Johannsen, 1937). Because Lake Superior test water used in the study was relatively soft (44.3 mg/L CaCO/sub 3/) and the concentrations of organic materials and particulates were also presumably low, the test water probably had a limited capacity for reducing silver toxicity by adsorption or complexation. The LC/sub 50/s of the study would represent values obtained under conditions resulting in relatively sensitive estimates of toxicity. (JMT)

QSAR Evaluation of .alpha.-Terthienyl Phototoxicity.

The concept that phototoxic chemicals can be identified in chemical risk assessments by computing the energy difference between highest occupied and lowest unoccupied molecular orbitals (HOMO-LUMO gap) was evaluated using two new sets of phototoxicity data from the recent literature. The original model, developed from data with unsubstituted PAH toxicity to Daphnia magna, showed that phototoxicity was observed when the HOMO-LUMO gap varied between 6.7 and 7.5 eV. All substituted α-terthienyls that were phototoxic to mosquito larvae and to brine shrimp had HOMO-LUMO gap energies within the 7.1 10.4 eV «phototoxicity window». The α-terthienyls within this range that did not exhibit phototoxicity contained carboxyl or other polar substituents, which likely prevented bioaccumulation in the organisms. Polyamino and polynitro derivatives of toluene in munitions wastes were reported to be phototoxic to sea urchins even though the HOMO-LUMO gap energies exceeded 8.0 eV. Because the same toluenes were not phototoxic to D. magna nor to Escherichia coli, we suggest that the developmental effects observed in the sea urchins were caused by electrophilic species from metabolic activation rather than the production of oxygen radicals from photo induced excited states of the molecules

QSAR Estimates of Excited States and Photoinduced Acute Toxicity of Polycyclic Aromatic Hydrocarbons

Abstract Direct calculation of the energy of excited states for polycyclic aromatic hydrocarbons using semi-empirical methods on a supercomputer were inadequate in explaning spectrosopic data or measured phototoxicity. The energy difference between frontier orbitals HOMO-LUMO gap of “average” excited state structures of the PAHs correlated with the measured excited state energies and their observed photoinduced toxicity. The multi-linear relationship between phototoxicity and hypothetical triplet state HOMO-LUMO gap is similar to that based on ground state structures. This molecular descriptor discriminated phototoxic PAHs into a narrow range of approximately 6.2+ mn;0.4 eV. Chemicals with a HOMO-LUMO gap in the triplet state greater than 7.1 eV were not phototoxic in simulated sunlight. Chemicals with gaps less than 5.8 eV are likely to be unstable in water and degrade too rapidly to enable determination of photoinduced potency to aquatic organisms. Several preliminary structure-phototoxicity relationshi...