Adverse outcome pathway of developmental neurotoxicity resulting from prenatal exposures to cannabis contaminated with organophosphate pesticide residues.

There is growing concern that increased use of medical and recreational cannabis may result in increased exposure to contaminants on the cannabis, such as pesticides. Several states are moving towards implementing robust regulation of the sales, cultivation, and manufacture of cannabis products. However, there are challenges with creating health-protective regulations in an industry that, to date, has been largely unregulated. The focus of this publication is a theoretical examination of what may happen when women are exposed pre-conceptually or during pregnancy to cannabis contaminated with pesticides. We propose an adverse outcome pathway of concomitant prenatal exposure to cannabinoids and the organophosphate pesticide chlorpyrifos by curating what we consider to be the key events at the molecular, cellular, and tissue levels that result in developmental neurotoxicity. The implications of this adverse outcome pathway underscore the need to elucidate the potential developmental neurotoxicity that may result from prenatal exposure to pesticide-contaminated cannabis.

Influence of pH and natural organic matter on zinc biosorption in a model lignocellulosic biofuel biorefinery effluent.

The effect of dissolved natural organic matter (NOM) and pH on microbial biosorption of Zn was evaluated in a model lignocellulosic biofuel refinery effluent rich in NOM. Batch culture experiments conducted with two model microorganisms (yeast, Candida tropicalis; bacteria Novosphingobium nitrogenifigens Y88(T)), showed an inhibitory effect of NOM, and an optimum pH for Zn removal at 7.5-8.0. Membrane bioreactors with mixed autochthonous organisms were operated at pH 6.5 and pH 8.0 to better simulate real-world remediation scenarios. More Zn was removed at the high (91%) than at the low (26%) pH, presumably because the higher pH freed negatively-charged functional groups on the cellular biomass for passive Zn binding. Manipulating the pH of bioreactors can significantly improve metal removal in NOM rich wastewater. Such reactors could maintain water quality for closed-cycle biorefineries, leading to reduced water consumption, and a more sustainable biofuel.

Metal biosorption in lignocellulosic biofuel biorefinery effluent: an initial step towards sustainability of water resources.

Biosorption of metals by microorganisms is a promising technology to remove accumulated non-process elements in highly recycled biorefinery process water. Removal of these elements would enable greater water reuse and reduce the environmental impact of effluent discharge. A model lignocellulosic ethanol biorefinery wastewater was created based on pulp mill effluent. This generated a wastewater with an environmentally realistic high loading of dissolved natural organic matter (900 mg/l), a potentially important factor influencing metal biosorption. Analysis of feedstock and pulp mill effluent indicated that Mn and Zn are likely to be problematic in highly recycled lignocellulosic ethanol biorefinery process water. Therefore, the growth of several bacteria and fungi from existing collections, and some isolated from pulp mill effluent were tested in the model wastewater spiked with Mn and Zn (0.2 mM). Wastewater isolates grew the best in the wastewater. Metal uptake varied by species and was much greater for Zn than Mn. A bacterium, Novosphingobium nitrogenifigens Y88(T), removed the most metal per unit biomass, 35 and 17 mg Mn/g. No other organism tested decreased the Mn concentration. A yeast, Candida tropicalis, produced the most biomass and removed the most total metal (38 % of Zn), while uptake per unit biomass was 24 mg Zn/g. These results indicate that microorganisms can remove significant amounts of metals in wastewater with high concentrations of dissolved natural organic matter. Metal sorption by autochthonous microorganisms in an anaerobic bioreactor may be able to extend water reuse and therefore lower the water consumption of future biorefineries.

Aquatic life water quality criteria derived via the UC Davis method: I. Organophosphate insecticides.

A new methodology for deriving freshwater aquatic life water quality criteria,developed by the University of California Davis, was used to derive criteria for three organophosphate insecticides. The UC Davis methodology resulted in similar criteria to other accepted methods, and incorporated new approaches that enable criteria generation in cases where the existing USEPA guidance cannot be used.Acute and chronic water quality criteria were derived for chlorpyrifos (10 and 10 ng/L, respectively), diazinon (200 and 70 ng/L, respectively), and malathion(170 and 28 ng/L, respectively). For acute criteria derivation, Burr Type III SSDs were fitted to the chlorpyrifos and diazinon acute toxicity data sets while an alternative assessment factor procedure was used for malathion because that acute data set did not contain adequate species diversity to use a distribution.ACRs were used to calculate chronic criteria because there was a dearth of chronic data in all cases, especially for malathion, for which there was a lack of paired acute and chronic invertebrate data. Another alternate procedure enabled calculation of the malathion chronic criterion by combining a default ratio with the experimentally derived ratios. A review of the diazinon chronic criterion found it to be under protective of cladoceran species, so a more protective criterion was calculated using a lower distributional estimate. The acute and chronic data sets were assembled using a transparent and consistent system for judging the relevance and reliability of studies, and the individual study review notes are included.The resulting criteria are unique in that they were reviewed to ensure particular protection of sensitive and threatened and endangered species, and mixture toxicity is incorporated into criteria compliance for all three compounds.For chlorpyrifos and diazinon, the UCDM generated criteria similar to the long-standing USEPA (1985) method, with less taxa requirements, a more statistically robust distribution, and the incorporation of new advances in risk assessment and ecotoxicology. According to the USEPA (1985) method, the data set gathered for malathion would not be sufficient to calculate criteria because it did not contain data for a benthic crustacean. Benthic crustacean data is also required to use a distributional calculation method by the UCDM, but when data is lacking the UCDM provides an alternate calculation method." The resulting criteria are associated with higher, unquantifiable uncertainty, but they are likely more accurate than values generated using static safety factors, which are currently common in risk assessment.

Aquatic life water quality criteria derived via the UC Davis method: II. Pyrethroid insecticides.

Aquatic life water quality criteria were derived for five pyrethroids using a new methodology developed by the University of California, Davis (TenBrook et al.2010). This methodology was developed to provide an updated, flexible, and robust water quality criteria derivation methodology specifically for pesticides. To derive the acute criteria, log-logistic SSDs were fitted to the medium-sized bifenthrin,cyfluthrin, and cypermethrin acute toxicity data sets while the X-cyhalothrin and permethrin acute data sets were larger, and Burr Type III SSDs could be fitted to these data sets. A review of the cyfluthrin acute criterion revealed that it was not protective of the most sensitive species in the data set, H. azteca, so the acute value was adjusted downward to calculate a more protective criterion. Similarly, the cypermethrin criteria were adjusted downward to be protective of H. azteca.Criteria for bifenthrin, X-cyhalothrin, and permethrin were calculated using the median fifth percentile acute values while the cyfluthrin and cypermethrin criteria were calculated with the next lowest acute value (median first percentile). Chronic data sets were limited in all cases, so ACRs were used for chronic criteria calculations, instead of statistical distributions. Sufficient corresponding acute and chronic data were not available for bifenthrin, cypermethrin, or permethrin, so a default ACR was used to calculate these chronic criteria while measured ACRs were used for cyfluthrin and X-cyhalothrin. A numeric scoring system was used to sort the acute and chronic data, based on relevance and reliability, and the individual study scores are included in the Supporting Information.According to the USEPA (1985) method, the data sets gathered for these five pyrethroids would not be sufficient to calculate criteria because they were each missing at least one of the eight taxa required by that method. The USEPA (1985)method generates robust and reliable criteria, and the goal of creating the UCDM was to create a method that also yields statistically robust criteria, but with more flexible calculation methods to accommodate pesticide data sets of varied sizes and diversities. Using the UCDM, acute and chronic water quality criteria were derived for bifenthrin (4 and 0.6 ng/L, respectively), cyfluthrin (0.3 and 0.05 ng/L, respectively), cypermethrin (1 and 0.2 ng/L, respectively), X-cyhalothrin (1 and 0.5 ng/L,respectively), and permethrin (10 and 2 ng/L, respectively). Water quality criteria for these five pyrethroids can be used by environmental managers to control the increasing problem of surface water contamination by pesticides.

Reduction of vitellogenin synthesis by an aryl hydrocarbon receptor agonist in the white sturgeon (Acipenser transmontamus).

Migrating white sturgeon (Acipenser transmontamus) may be subject to agricultural, municipal, and industrial wastewater effluents that likely contain different classes of endocrine-disrupting contaminants. Concern is mounting about the negative effects of environmental estrogens on fish reproduction; however, in environmental mixtures, the affects from estrogenic compounds may be suppressed by aryl hydrocarbon receptor (AhR) ligands. Indeed, reductions in 17beta-estradiol-induced (0.01 and 1 mg/kg) vitellogenin (VTG) levels were observed in white sturgeon coinjected with beta-naphthoflavone (BNF; 50 mg/kg), a model for contaminants that activate the AhR. Variation in the time of injection was used to attempt to correlate VTG inhibition to ethoxyresorufin-O-deethylase activity. No evidence was found to suggest that the inhibition of VTG is a direct result of enhanced estrogen metabolism by BNF-induced enzymes. Results of the present study are relevant for monitoring programs that measure VTG, because these results show that AhR-active environmental contaminants can repress VTG synthesis, which commonly is used as an indicator of estrogen-mimicking contaminants. Furthermore, suppression of natural estrogen signaling by AhR agonists may have significant effects on fish reproduction.

Optimization and validation of a California halibut environmental estrogen bioassay using a heterologous ELISA.

Vitellogenin, the estrogen-inducible yolk protein precursor, serves as an indicator of exposure to estrogen mimicking environmental contaminants. An ELISA for the measurement of California halibut plasma vitellogenin was optimized and validated using a commercially-available antibody developed for another flatfish species, turbot. Attempts to enhance assay performance by addition of a biotinylated antibody, polyethylene glycol, and Tween-20, and altering the preincubation step are described. Inclusion of overnight preincubation was critical for low detection limits. Increasing the amount of Tween-20 to 0.05% in buffers was most effective in achieving accurate quantification of spiked plasma samples. At the IC50, the average recovery of spiked plasma samples was 104% and the interplate CV was 12%. The working range of the assay was 33-1000 ng/mL, while the detection limit in a plasma sample is 2.2 microg/mL. The performance of this assay compared very well to a homologous assay demonstrating that commercially-available antibodies can facilitate the development of bioassays for local environmentally-relevant species. The dose response relationship of halibut Vg to the model compounds 17beta-estradiol and pnonylphenol show that it is a suitable model for further studies of estrogen mimicking contaminants.

Influence of phosphate and copper on reductive dechlorination of thiobencarb in California rice field soils.

The potential for reductive dechlorination of the herbicide thiobencarb (TB) by microbes and its prevention in saturated anaerobic rice field soils was examined in laboratory microcosms. TB is effective in controlling both annual grasses and broadleaf weeds. In anoxic microcosms, TB was effectively degraded within 30 days to its dechlorinated product, deschlorothiobencarb (DTB), in two Sacramento Valley rice field soils. TB dechlorination, and subsequent degradation, followed pseudo-zero- (lag phase) and first-order (degradation phase) kinetics. Logistic regression analysis (r2 > 0.841) produced a half-life (t(1/2)) in nonsterile soils ranging from 10 to 15 days, which was also observed when microcosms were amended with low concentrations (<3 mg L(-1)) of copper (Cu2+; as the fungicides Cu(OH)2 and CuSO4.5H2O). High Cu2+ concentrations (>40 mg L(-1)) were added to the microcosms to determine if copper toxicity to dechlorinating microbes is concentration dependent within the range used. After 30 days, the low-copper-amended soils closely resembled the nonsterile experiments to which no Cu2+ was added while the high-copper-amended microcosms were similar to the sterile experiment. Microcosms were also separately amended with 5.7 g L(-1) phosphate (PO4(2-); as KH2PO4), a nutrient regularly applied to rice fields. Phosphate-amended experiments also showed TB degradation, but no DTB formation, indicating the phosphate played a role, possibly as a microbial inhibitor or an alternative electron acceptor, in limiting the dechlorination of TB. In summary, TB dechlorination was inhibited at high Cu(OH)2, CuSO4.5H2O, and KH2PO4 concentrations.