Estimation Of Chronic Toxicity Research Articles

Evidence for Specific Receptor-Mediated Toxicity of Pharmaceuticals in Aquatic Organisms Derived from Acute and Chronic Standard Endpoints.

The toxicity of 17 active pharmaceutical ingredients (APIs) was investigated using standardized acute and chronic tests with Daphnia magna and 2 algae species. Chronic toxicity was generally greater for Daphnia than for algae. Compilation of additional data resulted in 100 APIs for which the acute-to-chronic ratio (ACR) was determined for Daphnia. The frequency of high ACRs (~20% with ACRs > 100) indicates that specific receptor-mediated toxicity toward D. magna is rather common among APIs. The 11 APIs with ACRs > 1000 included lipid-modifying agents, immunosuppressants, antibiotics, antineoplastics, antiobesics, antivirals, and antihistamines. There was no consistent association between ACR and chronic toxicity, ionization status, or lipophilicity. High ACRs were not exclusively associated with the presence of orthologs of the pharmacological target in Daphnia. Statins, acetylcholinesterase inhibitors, and antihistamines are discussed in more detail regarding the link between targets and toxic mode of action. For acetylcholinesterase inhibitors, receptor-mediated toxicity was already apparent after acute exposure, whereas the high ACR and chronic toxicity of some antihistamines probably related to interaction with a secondary rather than the primary pharmacological target. Acute or modeled chronic toxicity estimates have often been used for prioritizing pharmaceuticals. This may be seriously misleading because chronic effects are currently not predictable for APIs with specific receptor-mediated toxicity. However, it is exactly these APIs that are the most relevant in terms of environmental risks. Environ Toxicol Chem 2022;41:601-613. © 2021 SETAC.

Ecological risk assessment for perfluorooctanoic acid in soil using a species sensitivity approach

Perfluorooctanoic acid (PFOA) is one of the persistent organic pollutants that has been listed in Annex A of the Stockholm Convention and has attracted attention owing to its endocrine-disrupting properties. However, there is currently little information available regarding the soil ecotoxicity of PFOA and the associated ecological risks. Accordingly, in this study, we sought to assess the soil ecological risk of PFOA based on a probabilistic approach using data obtained from multispecies bioassays and soil toxicity assessments, from which we generated soil species sensitivity distributions and estimated soil protective concentrations for PFOA. Using the latter distributions, we also undertook a probabilistic ecological risk assessment. On the basis of acute and chronic toxicity estimates obtained from bioassays involving eight soil-associated organisms from six diverse taxonomic groups, we could deduce that PFOA poses a negligible risk to soil ecosystems. However, we also found that this chemical may be more toxic than some of the established endocrine-disrupting chemicals such as bisphenol A, nonylphenol, and methylparaben, thereby indicating that further in-depth studies would be necessary to obtain a better understanding of the toxic potential of this chemical in the soil environment.

Chronic ammonia toxicity to juveniles of 2 tropical Australian freshwater mussels (Velesunio spp.): Toxicity test optimization and implications for water quality guideline values.

Freshwater mussels play key roles in aquatic ecosystems, but are experiencing a global decline. Although studies have reported high acute sensitivity of mussels to some contaminants, chronic toxicity data are lacking for deriving high-reliability water quality guideline values. Ammonia is a contaminant of potential concern in some catchments of tropical northern Australia, where freshwater mussels are important ecological and cultural components. The extremely soft waters (hardness < 5 mg/L) of these environments can result in increased toxicity of many contaminants including ammonia, and regionally relevant tropical guideline values are needed to adequately protect these unique ecosystems. An optimized 14-d toxicity test protocol was used to assess the chronic toxicity of ammonia for 2 species, the lotic Velesunio sp. and the lentic Velesunio angasi. Ammonia exposures were conducted at pH 6.0 and 27 ± 0.5 °C to represent local environmental conditions, using shell length growth rate as the endpoint. Chronic toxicity estimates indicated high sensitivity to ammonia, with mean median effect concentrations (in total ammonia nitrogen) being 7.0 mg/L for V. angasi from the semi-urbanized Lake Bennett, 9.2 mg/L for V. angasi from Sandy Billabong, and 11.3 mg/L for Velesunio sp. from Gulungul Creek. When the 10% effect concentration values were compared with other chronic ammonia data (normalized to pH 7.0 and 20 °C), Velesunio spp. were found to be more sensitive than 8 of 16 other temperate and 7 of 9 tropical invertebrate and fish species. These chronic toxicity estimates will be used to further inform regionally relevant and site-specific guideline values. Environ Toxicol Chem 2019;38:841-851. © 2019 Commonwealth of Australia. Published by Wiley Periodicals Inc. on behalf of SETAC.

Toxicity of aqueous vanadium to zooplankton and phytoplankton species of relevance to the athabasca oil sands region

Vanadium (V) is an abundant trace metal present in bitumen from the Athabasca Oil Sands (AOS) region in Alberta, Canada. The upgrading of bitumen can result in the production of large volumes of a carbonaceous material referred to as petroleum coke that contains V at elevated levels compared to the native bitumen. Previous studies have shown that coke has the capacity to leach ecotoxicologically relevant levels of V into water it contacts, yet limited data are available on the toxicity of aqueous V to planktonic organisms. Therefore, this study set out to evaluate the acute and chronic toxicity of V (as vanadate oxyanions) to freshwater zooplankton and phytoplankton species that are either commonly-used laboratory species, or species more regionally-representative of northern Alberta. Four cladoceran (2-d and 21-d tests) and two algal (3-d tests) species were exposed to V to obtain both acute and chronic toxicity estimates. Acute V toxicity (LC50s) ranged from 0.60mgV/L for Ceriodaphnia quadrangula to 2.17mgV/L for Daphnia pulex. Chronic toxicity estimates (EC50s) for cladoceran survival and reproduction were nearly identical within species and ranged from a low of 0.13 to a high of 0.46mgV/L for Daphnia dentifera and D. pulex, respectively. The lack of sublethal V toxicity in daphnia suggests a direct mechanism of toxicity through ion imbalance. Growth inhibition (EC50) of green algae occurred at concentrations of 3.24 and 4.12mgV/L for Pseudokirchneriella subcapitata and Scenedesmus quadricauda, respectively. Overall, cladocerans were more sensitive to V than green algae, with survival of the field-collected D. dentifera being approximately 2.5 to 3.5 times more sensitive to acute and chronic V exposure than the standard test species D. pulex. However, there were no significant differences in V toxicity between the field-collected cladocerans Simocephalus serrulatus and C. quadrangula, compared to the respective standard species D. pulex and Ceriodaphnia dubia. Similarly, there were no significant differences in sensitivity to V in the two algal species evaluated. Based on V concentrations reported in laboratory-generated coke leachates, zooplankton survival could be adversely impacted under conditions of chronic leachate exposure if V concentrations in the environment exceed 0.1mg/L. Furthermore, toxicity thresholds from commonly-used planktonic test species would likely have sufficed for derivation of a V water quality guideline (WQG) for protection of local aquatic communities near oil sands operations, but the new data presented here on V toxicity to more regionally-representative species will strengthen the database for WQG derivation.

Accuracy of chronic aquatic toxicity estimates determined from acute toxicity data and two time–response models

Traditionally, chronic toxicity in aquatic organisms and wildlife has been determined from either toxicity test data, acute to chronic ratios, or application of safety factors. A more recent alternative approach has been to estimate chronic toxicity by modeling the time course of mortality as determined in standard acute toxicity tests, but these approaches have received limited validation. The accuracy of chronic toxicity estimates from two time-response models, linear regression analysis (LRA) and accelerated life testing (ALT), was investigated using a dataset of more than 150 matched species pairs of standard acute toxicity test data and measured chronic no-observed-effect concentrations (NOECs). Chronic survival was more accurately modeled by both ALT (accuracy, 69%) and LRA (accuracy, 76%) than was reproduction, growth, or the most sensitive endpoint (accuracy, 50-60%). In general, LRA estimates of chronic toxicity were less conservative than ALT estimates, with 66 to 79% of LRA estimates being greater than the measured NOEC. Acute datasets with early mortality produced estimates of chronic survival that were more accurate (ALT, 92%; LRA, 89%) compared to all datasets but were less conservative (84% of ALT estimates were overestimated vs 93% of LRA estimates). Acute datasets with late mortality resulted in poor ALT and LRA estimates of chronic toxicity for all endpoints. Additional survival time measurements did not improve the accuracy of ALT or LRA estimates of chronic toxicity over the standard four acute measurement times (24, 48, 72, and 96 h). The time course of mortality should be considered when applying time-response models to estimate chronic aquatic toxicity, with greater accuracy likely for chronic survival than for growth or reproduction.