Exposure to UV-B filter octylmethoxycinnamate and human health effects: Focus on endocrine disruptor actions.

Human skin is the first line of photoprotection against UV radiation. However, despite having its defence mechanisms, the photoprotection that the skin exerts is not enough. To protect human skin, the inclusion of UV filters in the cosmetic industry has grown significantly as a photoprotection strategy. Octylmethoxycinnamate, also designated by octinoxate, or 2-ethylhexyl-4-methoxycinnamate (CAS number: 5466-77-3) is one of the most widely used UV-B filter in the cosmetic industry. The toxic effects of OMC have alarmed the public, but there is still no consensus in the scientific community about its use. This article aims to provide an overview of the UV filters' photoprotection, emphasizing the OMC and the possible negative effects it may have on the public health. Moreover, the current legislation will be addressed. In summary, the recommendations should be rethought to assess their risk-benefit, since the existing literature warns us to endocrine-disrupting effects of OMC. Further studies should be focus on the toxicity of OMC alone, in mixture and should consider its degradation products, to improve the knowledge of its risk assessment as EDC.

Effects associated with exposure to the emerging contaminant octyl-methoxycinnamate (a UV-B filter) in the aquatic environment: a review.

Given the increasing concern surrounding ultraviolet (UV) radiation-induced skin damage, there has been a rise in demand for UV filters. Currently, UV-filters are considered emerging contaminants. The extensive production and use of UV filters have led to their widespread release into the aquatic environment. Thus, there is growing concern that UV filters may bioaccumulate and exhibit persistent properties within the environment, raising several safety health concerns. Octyl-methoxycinnamate (OMC) is extensively employed as a UV-B filter in the cosmetic industry. While initially designed to mitigate the adverse photobiological effects attributed to UV radiation, the safety of OMC has been questioned with some studies reporting toxic effects on environment. The aim of this review to provide an overview of the scientific information regarding the most widely used organic UV-filter (OMC), and its effects on biodiversity and aquatic environment.

UV-B Filter Octylmethoxycinnamate Is a Modulator of the Serotonin and Histamine Receptors in Human Umbilical Arteries.

Every day, people use personal care products containing UV filters. Although their use initially showed a protective role, toxicity is a concern for human health as several UV filters are endocrine-disrupting chemicals (EDCs). Exposure to EDCs may induce cardiovascular diseases and can affect the health of sensitive people, such as pregnant women. Currently, the world's most widely used UV-B filter is octylmethoxycinnamate (OMC), an EDC. However, the disruptive effects on pregnant women are little known. The present work proposed to understand how long-term exposure to OMC affects vascular homeostasis. Endothelium-denuded human umbilical artery (HUA) rings were incubated in an organ bath system. Long-term effects of exposure to OMC (0.001-50 µmol/L) were evaluated on the contractile responses of HUA to the application of the contractile agents, serotonin (5-HT) and histamine (Hist). To investigate in more detail the vascular mode of action of OMC, through which it impairs the vascular homeostasis of HUA, the activity and expression of different 5-HT and Hist-receptors involved in contractility processes were studied. Our findings pointed out an increase in the reactivity of HUA to 5-HT and Hist due to OMC exposure. These alterations in reactivity may be precursors of preeclampsia development and/or gestational hypertension.

UV-B filter octylmethoxycinnamate impaired the main vasorelaxant mechanism of human umbilical artery.

Personal care products (PCPs) are a group of diverse substances widely used daily for health, beauty, and cleanliness. More than 90% of all PCPs contain the UV-B filter octylmethoxycinnamate (OMC) as a protective function, however, their safety has recently been questioned. The purpose of the present work was to understand how the long-term exposure of UV-filter OMC, used daily by pregnant women, disrupts their vascular homeostasis, altering vascular responses of proteins and channels involved in contractile processes. The long-term effects of 24 h of exposure to OMC (1, 10, and 50 µmol/L) were evaluated on contractile responses of human umbilical arteries (HUA) to serotonin and potassium chloride. Since OMC altered vascular homeostasis of arteries, its vascular mode of action was explored in more detail through the analysis of the activity of cGMP and Ca2+-channels, two pathways involved in their relaxation and contraction, respectively. Our findings showed that long-term exposure of UV-filter OMC impaired the main vasorelaxant mechanism of HUA, once OMC altered the vasorelaxant response pattern of sodium nitroprusside and nifedipine. Results also showed that long-term exposure to OMC induced a decreased vasorelaxation response on HUA due to an interference with the NO/sGC/cGMP/PKG pathway. Moreover, OMC seems to modulate the L-type Ca2+ channels, the BKCa 1.1 α-subunit channels, and the PKG. Overall, since OMC compromises the vascular homeostasis of pregnant women it can be an inductor of pregnancy hypertensive disorders.

UV-B Filter Octylmethoxycinnamate Alters the Vascular Contractility Patterns in Pregnant Women with Hypothyroidism.

Increasing evidence relating the exposure and/or bioaccumulation of endocrine-disrupting compounds (EDCs) with cardiovascular system are arising. Octylmethoxycinnamate (OMC) is the most widely used UV-B filter and as EDC interacts with TH receptors. However, their effects on thyroid diseases during pregnancy remain unknown. The purpose of this work was to assess the short- and long-term effects of OMC on arterial tonus of pregnant women with hypothyroidism. To elucidate this, human umbilical artery (HUA) rings without endothelium were used to explore the vascular effects of OMC by arterial and cellular experiments. The binding energy and the modes of interaction of the OMC into the active center of the TSHR and THRα were analyzed by molecular docking studies. Our results indicated that OMC altered the contractility patterns of HUA contracted with serotonin, histamine and KCl, possibly due to an interference with serotonin and histamine receptors or an involvement of the Ca2+ channels. The molecular docking analysis show that OMC compete with T3 for the binding center of THRα. Taken together, these findings pointed out to alterations in HUA reactivity as result of OMC-exposure, which may be involved in the development and increased risk of cardiovascular diseases.

Effects of ultraviolet radiation to Solea senegalensis during early development.

Ultraviolet radiation (UVR) reaching the Earth surface is increasing and scarce information is available regarding effects of this stressor to early life stages of marine vertebrates. Therefore, this work aims to study the effects of UVR exposure during early development stages of the flatfish Solea senegalensis. Firstly, fish were exposed to UVR (six daily doses between 3.4 ±â€¯0.08 and 8.6 ±â€¯0.14 kJ m-2) at the following moments: gastrula stage (24 h post fertilization, hpf), 1 and 2 days after hatching (dah, 48 and 72 hpf, respectively). In a second bioassay, fish at the beginning of metamorphosis were exposed to UVR (one or two daily doses of 7.2 ±â€¯0.39 or 11.1 ±â€¯0.49 kJ m-2) and then maintained until the end of metamorphosis. Mortality and effects on development, growth and behaviour were evaluated at the end of both bioassays (3 dah and 18 dah, respectively). Biomarkers of neurotransmission (acetylcholinesterase, AChE), oxidative stress (catalase, CAT) and biotransformation (glutathione S-transferase, GST) were also determined at the end of the early larvae bioassay, and metamorphosis progression was evaluated during the second bioassay. UVR exposure caused distinct effects depending on life stage. Altered pigmentation, decreased growth, impaired fish behaviour and AChE and GST inhibition were observed at the earlier larval phase. Whereas, decrease in growth was the main effect observed at the metamorphosis stage. In summary, the exposure of S. senegalensis early stages to environmentally relevant UVR doses led to adverse responses at different levels of biological organization, which might lead to implications in later life stages.

UV-B Filter Octylmethoxycinnamate Induces Vasorelaxation by Ca2+ Channel Inhibition and Guanylyl Cyclase Activation in Human Umbilical Arteries.

Ultraviolet (UV) filters are chemicals widely used in personal care products (PCPs). Due to their effect as endocrine disruptor compounds (EDCs), the toxicity of UV filters is a current concern for human health. EDC exposure may be correlated to cardiovascular diseases (CVD), but to our knowledge, no studies assessed the UV filters effects as human EDCs at the vascular level. Octylmethoxycinnamate (OMC) is the world's most widely used UV-B filter, present in more than 90% of PCPs. Due to its demonstrated multiple hormonal activities in animal models, this substance is also suspected to be a human EDC. The purpose of this study was to assess the rapid/short-term effects of OMC on arterial tonus and analyse its mode of action (MOA). Using human umbilical arteries, the endocrine effects of OMC were evaluated in in vitro (cellular and organ) experiments by planar cell surface area (PCSA) and organ bath, respectively. Our data show that OMC induces a rapid/short-term smooth muscle relaxation acting through an endothelium-independent MOA, which seems to be shared with oestrogens, involving an activation of soluble guanylyl cyclase (sGC) that increases the cyclic guanosine monophosphate (cGMP) intracellular levels and an inhibition of L-type voltage-operated Ca2+ channels (L-Type VOCC).

Effects of PCB-77 in adult zebrafish after exposure during early life stages.

Polychlorinated biphenyls (PCBs) are a class of industrial chemicals that cause endocrine changes, since they are able to bind to estrogen receptors and interfere with estrogen-regulated processes, such as fish vitellogenesis. Therefore, the present work aimed to assess potential endocrine effects of PCB-77 exposure during zebrafish (Danio rerio) gonadal differentiation. To achieve that, zebrafish juveniles were exposed to increasing concentrations of PCB-77 for 14 days during a critical window of gonad differentiation (30-44 days post-fertilization). Vitellogenin (Vtg) levels and several endpoints such as survival, growth, gonadosomatic index (GSI) and hepatosomatic index were recorded at the end of exposure and/or after 3 months in clean medium. The results obtained showed a reduction of Vtg-like proteins in juveniles, just after exposure to PCB-77 accompanied, after 3 months, by a decrease in gonadal Vtg levels and GSI of females. These results suggest that exposure to PCB-77 during the critical window of gonadal differentiation decreased vitellogenesis in juvenile zebrafish which lasted until adulthood affecting the normal development of female gonad, which might have further implications in reproduction success.

Toxicity effects of the organic UV-filter 4-Methylbenzylidene camphor in zebrafish embryos.

Ultraviolet (UV) filters are widely used in personal care products and due to their lipophilicity these chemicals tend to bioaccumulate in the aquatic biota. 4-Methylbenzylidene camphor (4-MBC) is one of the most used UV-filters, and it is commonly detected in freshwater fish tissues. This substance is suspected to be an endocrine disruptor due to its interaction with Hypothalamus-Pituitary-Gonadal (HPG) and HP-Thyroid (HPT)-axis. The main objective of this study was to evaluate the effects of 4-MBC on apical endpoints, biochemical markers and on genes involved in endocrine pathways in Danio rerio. Zebrafish embryos were exposed to 4-MBC (0.083-0.77 mg/l) from 0 to 96 h post-fertilization (hpf). Hatching, heart rate and malformations were the apical endpoints assessed. Alterations on neurotransmission and oxidative stress were evaluated through acetylcholinesterase (AChE), catalase (CAT) and glutathione S-transferase (GST) enzymatic activities. Endocrine effects were analysed by the expression of genes involved in HPG and HPT-axis of embryos exposed 96 h to the EC10 of 4-MBC (0.19 mg/l). Exposure to 4-MBC induced morphological abnormalities during embryonic development, including notochord curvature, delayed absorption of yolk sac and pericardial oedema. Concentration of 0.77 mg/l 4-MBC decreased embryo heart rate at 48h. At neurotransmission level, an induction of AChE at concentrations above 0.15 mg/l was observed. Malformations and decreased heart rate along with alterations observed at neurotransmission level might have compromised zebrafish larvae equilibrium. Glutathione S-transferase induction above 0.15 mg/l 4-MBC suggests activation of detoxification processes. Furthermore, observed brain aromatase gene down-regulation by 4-MBC suggests impairment of normal functioning of HPG axis in zebrafish.

Kleptoplast photoacclimation state modulates the photobehaviour of the solar-powered sea slug Elysia viridis.

Some sacoglossan sea slugs incorporate intracellular functional algal chloroplasts (kleptoplasty) for periods ranging from a few days to several months. Whether this association modulates the photobehaviour of solar-powered sea slugs is unknown. In this study, the long-term kleptoplast retention species Elysia viridis showed avoidance of dark independently of light acclimation state. In contrast, Placida dendritica, which shows non-functional retention of kleptoplasts, showed no preference over dark, low or high light. High light-acclimated (HLac) E. viridis showed a higher preference for high light than low light-acclimated (LLac) conspecifics. The position of the lateral folds (parapodia) was modulated by irradiance, with increasing light levels leading to a closure of parapodia and protection of kleptoplasts from high light exposure. Furthermore, closure of parapodia occurred at higher irradiance in HLacE. viridis Our results strongly indicate that kleptoplast photoacclimation state modulates the photobehaviour of the solar-powered sea slug E. viridis.

Effects of the herbicides linuron and S-metolachlor on Perez's frog embryos.

Presence of pesticides in the environment and their possible effects on aquatic organisms are of great concern worldwide. The extensive use of herbicides in agricultural areas are one of the factors contributing to the known decline of amphibian populations. Thus, as non-target species, amphibians can be exposed in early life stages to herbicides in aquatic systems. In this context, this study aims to evaluate effects of increasing concentrations of two maize herbicides, linuron and S-metolachlor on embryos of the Perez' frog (Pelophylax perezi) during 192 h. Apical endpoints were determined for each herbicide: mortality, hatching rate, malformations and length. Frog embryos presented a LC50 of 21 mg/l linuron and 37.5 mg/l S-metolachlor. Furthermore, sub-lethal concentrations of both herbicides affected normal embryonic development, delaying hatching, decreasing larvae length and causing several malformations. Length of larvae decreased with increasing concentrations of each herbicide, even at the lower concentrations tested. Malformations observed in larvae exposed to both herbicides were oedemas, spinal curvature and deformation, blistering and microphtalmia. Overall, these results highlight the need to assess adverse effects of xenobiotics to early life stages of amphibians regarding beside mortality the embryonic development, which could result in impairments at later stages. However, to unravel mechanisms involved in toxicity of these herbicides further studies regarding lower levels of biological organisation such as biochemical and genomic level should be performed.

Energetic costs and biochemical biomarkers associated with esfenvalerate exposure in Sericostoma vittatum.

Pyrethroid insecticides have been used for decades and their worldwide market continues to increase, despite their high toxicity to non-target insects. Recent studies reveal that it is essential to investigate the secondary mechanisms of action of type II pyrethroids to understand their cellular effects on invertebrates. The aim of this study was to evaluate the lethality, behaviour and physiological alterations and energetic costs in caddisfly larvae exposed to environmentally relevant concentrations of esfenvalerate (ESF). ESF caused both mortality and feeding inhibition of exposed caddisfly larvae: nominal ESF 96 h LC50 was 2.29 µg/L; feeding activity was impaired at concentrations equal or above 0.25 µg/L. At the cellular level, glutathione-S-transferase (GST) activity was increased on caddisfly larvae exposed to 0.25 and 0.5 µg/L ESF, which might contribute to prevent oxidative damage since levels of lipid peroxidation (LPO) were not altered. The energy budget of exposed caddisfly larvae was impaired by exposure to 0.25 µg/L ESF since sugar and protein contents decreased, while a decline of energy consumption was observed. The analysis of feeding, energy reserves and consumption data through structural equation modelling (SEM) allowed to quantify the direct and indirect effects of ESF exposure on bioenergetics of caddisfly larvae. SEM analysis showed a strong negative direct influence of ESF onto feeding activity, sugars content and energy consumption, highlighting a significant positive relationship between sugars and protein contents. These results show that energy expenditure is related to oxidative defense mechanisms induced by ESF stress that may lead to deleterious effects on growth and development.

Toxicity of organic UV-filters to the aquatic midge Chironomus riparius.

Despite the frequent detection of organic ultraviolet-filters (UV-filters) in freshwater sediments, there is a lack of ecotoxicological data undermining a correct risk assessment for these emerging contaminants. The present study assessed the effects of three of the most commonly used UV-filters (benzophenone-3 - BP3; 3-(4-methylbenzylidene)camphor - 4-MBC and octocrylene - OC) on Chironomus riparius life history and biochemical responses. Standard ecotoxicological assays confirmed that all compounds impaired growth of C. riparius larvae and induced developmental effects such as delayed emergence and a reduction of imagoes weight. Concerning the biochemical responses analysed no evidences of oxidative damage in lipids or neurotoxicity (tested assessing acetylcholinesterase activity) were observed for any of the tested compounds. However, 4-MBC exposure induced a decrease in catalase activity and an increase in glutathione-S-transferase activity at 14.13mg/Kg while OC exposure caused an increase in total glutathione levels at 0.23 and 18.23mg/Kg. Exposure to all UV-filters tested, increased energy consumption on C. riparius with significant differences above 1.00mg/Kg for BP3, 0.09mg/Kg for 4-MBC and 2.13mg/Kg for OC. These results suggest that environmental relevant concentrations of UV-filters can cause deleterious effects to aquatic benthic species, such as C. riparius, and call for further research concerning effects of organic UV-filters on natural invertebrate communities and ecosystem functioning.

Effects of 4-MBC and triclosan in embryos of the frog Pelophylax perezi.

The widespread and increasing use of personal care products (PCPs) have led to environmental contamination by substances included in these products. These substances have been detected in aquatic compartments and shown to cause adverse effects on non-target aquatic organisms. In this work toxicity of the antimicrobial triclosan (TCS) and of the UV-filter 3-(4-methylbenzylidene) camphor (4-MBC) was assessed in the embryos of Perez' frog Pelophylax perezi. Lethal and sub-lethal parameters were evaluated in embryos in Gosner stage 8-9 exposed to 0.00013-1.3 mg/l of 4-MBC and 0.25-2.50 mg/l of TCS during 144 h. Survival, malformations, length and hatching were evaluated as apical endpoints. Biomarkers of neurotransmission, oxidative stress, energy metabolism and estrogenicity were determined at the biochemical level through the activities of cholinesterase (ChE), catalase (CAT), glutathione S-transferase (GST), lactate dehydrogenase (LDH) and levels of lipid peroxidation (LPO) and vitellogenin (Vtg). Embryo exposure to 4-MBC led to few developmental malformations (up to 3%) and a GST induction at 0.013 mg/l. Triclosan exposure reduced survival, delayed hatching (at 72 h) and development and induced malformations. In addiction ChE was inhibited in the highest concentrations tested and GST and LDH were induced at 0.79 mg/l, the LOEC registered for TCS in Perez' frogs. Overall, our study showed that TCS might exert adverse effects on P. perezi early life stages, but only at four orders of magnitude above the concentrations found in environment. Furthermore, our results highlight the need to assess PCPs toxicity at different levels of biological organization.

Exposure to chlorantraniliprole affects the energy metabolism of the caddisfly Sericostoma vittatum.

Caddisflies have been included in ecotoxicological studies because of their sensitivity and ecological relevance. The present study aimed to assess the sublethal effects of an anthranilic diamide insecticide, chlorantraniliprole (CAP), to Sericostoma vittatum. Used worldwide, CAP is a persistent compound that has been found in surface waters at concentrations from 0.1 µg/L to 9.7 µg/L. It targets the ryanodine receptors, and the present ecotoxicological assessment focused on biomarkers related to neurotransmission, biotransformation, oxidative stress damage, and endpoints related to energy processing (feeding, energy reserves, and cellular metabolism). Six days of exposure trials revealed that feeding activity was significantly decreased in S. vittatum larvae exposed to 0.9 µg/L CAP. Concomitantly, a reduction in cellular metabolism and a significant decrease in protein content were also observed in caddisfly larvae exposed to CAP, suggesting metabolic depression. The results show that sublethal concentrations of CAP can cause detrimental sublethal effects on S. vittatum total glutathione content at concentrations as low as 0.2 µg/L. Bioenergetics can be used to assess physiological effects of contaminants, and the present results show that exposure to low, environmentally relevant, concentrations of CAP alter energy acquisition and metabolism in nontarget aquatic insects with potential population level effects. Environ Toxicol Chem 2017;36:1584-1591. © 2016 SETAC.

Are insect repellents toxic to freshwater insects? A case study using caddisflies exposed to DEET.

Stream ecosystems face ever-increasing pressures by the presence of emergent contaminants, such as, personal care products. N, N-diethyl-3-methylbenzamide (DEET) is a synthetic insect repellent that is being found in surface waters environments in concentrations up to 33.4 µg/L. Information concerning DEET's toxicity in the aquatic environment is still limited and focused only on its acute effects on model species. Our main objective was to assess the effects of DEET exposure to a caddisfly non-target species using sub-lethal endpoints. For that, we chose Sericostoma vittatum, an important shredder in Portuguese freshwaters that has been already used in different ecotoxicological assays. Besides acute tests, S. vittatum were exposed during 6 days to a gradient of DEET concentrations (8, 18 and 40.5 mg/L) to assess effects on feeding behaviour and biochemical responses, such as, lipid peroxidation levels (LPO), catalase and acetylcholinesterase (AChE) activities, and also assess effects on energy reserves and consumption. Acute tests revealed a 48 h-LC50 of 80.12 mg/L and DEET exposure caused feeding inhibition with a LOEC of 36.80 mg/L. Concerning the biochemical responses, DEET caused no effects in LPO nor on catalase activity. A non-significant decrease in AChE activity was observed. Regarding energetic reserves, exposure to DEET caused a significant reduction in S. vittatum carbohydrates levels. These results add important information for the risk assessment of insect repellents in the aquatic environment and suggest that reported environmental concentrations of DEET are not toxic to non-target freshwater insects.

Responses of the aquatic midge Chironomus riparius to DEET exposure.

N,N-diethyl-3-methylbenzamide (DEET) is the active ingredient of many commercial insect repellents. Despite being detected worldwide in effluents, surface water and groundwater, there is still limited information on DEET's toxicity toward non-target aquatic invertebrates. Thus, our main objective was to assess the effects of DEET in the life cycle of Chironomus riparius and assess its biochemical effects. Laboratory assays showed that DEET reduced developmental rates (reduced larval growth, delayed emergence) of C. riparius larvae and also caused a decrease in the size of adult midges. Concerning the biochemical responses, a short exposure to DEET caused no effects in lipid peroxidation, despite the significant inhibition of catalase and glutathione-S-transferase activities and of total glutathione contents. Moreover, inhibition of acetylcholinesterase activity was also observed showing neurotoxic effects. Environmental risk assessment of insect repellents is needed. Our results showed moderate toxicity of DEET toward C. riparius, however, due to their mode of action, indirect ecological effects of DEET and of other insect repellents cannot be excluded and should be evaluated.

Physiological effects of essential metals on two detritivores: Atyaephyra desmarestii (Millet) and Echinogammarus meridionalis (Pinkster).

Freshwater ecosystems are essential for humans; however, input of several types of contamination has led to the degradation of these ecosystems. Thus, it is urgent to assess their health to allow actions for prevention and remediation. The level of trace metals can be enhanced by natural or anthropogenic sources. Essential metals, such as copper and zinc, become toxic when present in the environment above threshold concentrations. To evaluate the physiological effects of these 2 essential metals for 2 freshwater detritivores, the shrimp Atyaephyra desmarestii and the amphipod Echinogammarus meridionalis, acute tests were performed. Forty-eight hour median lethal concentration (LC50) values were estimated for these species using static bioassays with copper and zinc. Sublethal assays for both metals with several phases were also done to evaluate the effects on feeding behavior. The LC50 values of copper for the shrimp A. desmarestii and amphipod E. meridionalis were 0.128 mg/L and 0.050 mg/L and those of zinc were 7.951 mg/L and 11.860 mg/L, respectively. The results indicated that copper is more toxic to both species. Only E. meridionalis showed deleterious effects of copper on feeding rate. Zinc showed some tendency for feeding inhibition in both species. Environ Toxicol Chem 2016;35:1442-1448. © 2015 SETAC.

Sub-lethal toxicity of environmentally relevant concentrations of esfenvalerate to Chironomus riparius.

Integrative studies focused on sub-organismal responses to pyrethroid exposure are important to understand life history responses. In this study, the ecotoxicological effects of esfenvalerate (ESF) on Chironomus riparius were assessed using five biochemical biomarkers related to neurophysiological function (acetylcholinesterase) and oxidative stress (catalase; glutathione-S-transferase; total glutathione and lipid peroxidation). In addition, effects on cellular energy allocation were assessed and all results were compared with organismal level responses (larval growth, emergence and sex ratio). Exposure to sub-lethal concentrations of ESF caused the failure of C. riparius antioxidant defenses (inhibition of catalase activity and decreased levels of total glutathione), which was reflected as oxidative damage. C. riparius energy budget was decreased by exposure to ESF due to an increased energy consumption. Life cycle tests showed that exposure to ESF impaired C. riparius developmental rates and increased male:female ratios, thereby confirming its toxicity and potential population level effects at environmentally relevant concentrations.

Life history and biochemical effects of chlorantraniliprole on Chironomus riparius.

The need to overcome pesticide resistance has led to the development of novel insecticides such as chlorantraniliprole (CAP), an anthranilic diamide. CAP disrupts calcium homeostasis in nerve and muscle cells and is used in several agricultural crops due to its potency and selectivity. However, chronic toxicity data for aquatic invertebrates are limited. Our objective was to evaluate the toxicity of CAP at different levels of biological organization using Chironomus riparius. Organismal endpoints (survival, larval growth and emergence), and 5 biomarkers associated with important physiological functions (acetylcholinesterase - AChE; catalase - CAT; glutathione-S-transferase - GST; total glutathione - TG; and lipid peroxidation - LPO) were investigated. Effects of CAP on cellular energy allocation (CEA) were also assessed. Acute tests revealed a 48 h LC50 for C. riparius of 77.5 µg/L and life-cycle tests revealed a chronic LOEC of 3.1 µg/L based on effects on C. riparius larval growth and emergence. C. riparius females exposed as larvae to low concentrations of CAP emerged at a smaller size which might also translate into effects on reproduction. Chironomid larvae were not under oxidative stress, since short exposures to CAP did not affect LPO levels, despite the significant inhibition of GST (0.6-9.6 µg/L) and CAT (9.6 µg/L). It seems that detoxification of reactive intermediates and ROS is still achieved due to glutathione consumption, since TG levels were significantly decreased in organisms exposed to CAP (0.6-9.6 µg/L). Moreover, it was observed that CEA was disturbed due to increased activity of the electron transport system (ETS), suggesting extra energy expenditure in larvae. These results show that environmental concentrations of CAP can impair the fitness of C. riparius natural populations and at the same time that chironomids, as for most insecticides, are suitable test organisms to evaluate the organismal and biochemical effects of anthranilic diamides.