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ECOTOXICOLOGY · 2024 · IF 2.4

Chronic toxicity and intergenerational effects of N-(1,3-dimethylbutyl)-N’-phenyl-p-phenylenediamine (6PPD) exposure alone and in combination with Zn2+ on Daphnia magna (Cladocera)

Yang Liu,Liu Kexin,Shi Lina,Chen Ming,Liu Junyan,Dai Shiniu,Xi Yilong,Wen Xinli

N-(1,3-dimethylbutyl)-N’-phenyl-p-phenylenediamine (6PPD) and Zn 2+ , extensively used in the tire manufacturing process, are frequently detected in freshwater environments. However, the intergenerational effects of isolated 6PPD exposure and joint 6PPD and Zn 2+ exposure at concentrations approximating environmental levels remain unknown. This study assessed the chronic toxicity and intergenerational effects of 6PPD (0.02–20 μg/L) and a mixture of 6PPD and Zn 2+ (5 μg/L) over three generations in Daphnia magna bioassays. In the F0 generation, a dose-dependent decline in total offspring number was observed with 6PPD exposure alone, while co-exposure with Zn 2+ exacerbated the reproductive toxicity of 6PPD. Across three generations, low-dose (0.02 µg/L) 6PPD alone and combined with Zn 2+ induced a cumulative degenerative maternal effect. Conversely, high-dose (20 µg/L) 6PPD, both independently and in combination with Zn 2+ , exhibited an adaptive maternal effect. Notably, the grandmaternal effect emerged exclusively in the co-exposure group treated with 20 μg/L 6PPD and 5 μg/L Zn 2+ , with no such effect in the group exposed to 20 μg/L 6PPD alone, suggesting that Zn 2+ may enhance the potential toxicity of 6PPD. Overall, this study provides novel insight into the intergenerational impacts of environmentally relevant levels of 6PPD alone and in combination with a heavy metal, elucidating the environmental risks posed by tire-derived chemicals through their synergistic effects on transgenerational toxicity.

CAS / MDL: 7646-85-7 793-24-8
研究领域: 环境科学 · 毒理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Pharmacology · 2022 · IF 5.988

Acute, chronic, and genotoxic studies on the protopine total alkaloids of the Macleaya cordata (willd.) R. Br. in rodents

Dong Zhen,Tang Shu-sheng,Ma Xiao-lan,Tan Bin,Tang Zhao-shan,Li Chang-hong,Yang Zi-hui,Zeng Jian-guo

The protopine alkaloids are widely distributed within the opium poppy family and have a wide range of pharmacological effects. MPTA is a product of the protopine total alkaloids extracted from the Macleaya cordata (Willd.) R. Br. Previously, we reported good anti-inflammatory activity of MPTA as well as oral acute and sub-chronic toxicity studies in rats. In order to perform a systematic toxicological safety assessment of MPTA, oral acute toxicity, genotoxicity (bone marrow cell chromosome aberration test, sperm abnormality test, bone marrow cell micronucleus test, and rat teratogenicity test), and chronic toxicity in mice were performed in this study. In the oral acute toxicity test, the LD50 in ICR mice was 481.99 mg/kg, with 95% confidence limits ranging from 404.27 to 574.70 mg/kg. All three mutagenicity tests tested negative in the range of 60.25–241.00 mg/kg. The results of the teratogenicity test in rats showed no reproductive or embryonic developmental toxicity at only 7.53 mg/kg, which can be considered as a no observed effect level (NOEL) for the teratogenicity test. Therefore, MPTA is safe for use at the doses tested, but attention should be paid to the potential risk to pregnant animals and the safety evaluation and toxicity mechanisms in target animals should be further investigated.

研究领域: 毒理学 · 药理学 · 遗传学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF FOOD SCIENCE · 2025 ·Vol. 90 ·期 3 ·e70075 · IF 3.4

Toxicological evaluation of Chlamydomonas reinhardtii enriched with protoporphyrin IX

Xuefeng Qu,Qinxi Wang,Zemi Xie,Yuejin Wu,Yangjunna Zhang,Zhen Liu,Yin Wang

The Chlamydomonas reinhardtii (red) is a strain rich in protoporphyrin IX, which could be used as algal-derived novel sustainable nutritional sources. However, the safety research on C. reinhardtii (red) remains insufficient and further investigation is needed. In order to assess the safety of C. reinhardtii (red) and to expand its use in food applications, a series of toxicological safety evaluations were carried out to observe acute toxicity, subchronic toxicity and genotoxicity of C. reinhardtii (red). The C. reinhardtii (red) was administered to an acute oral toxicity test, mammalian micronucleus test, mouse chromosomal aberration test in Institute of Cancer Research (ICR) mice, and 90-day repeated-dose oral toxicity test in Sprague-Dawley (SD) rats. In the acute oral toxicological test, no mortality or abnormalities were observed in male and female rats, with an median lethal dose(Lethal Dose, 50%) (LD 50 ) exceeding 10.0 g/kg body weight (BW). Similarly, male and female mice exhibited no mortality or abnormalities, with an LD 50 surpassing 20.0 g/kg BW. The results of bacterial reverse mutation test, mammalian micronucleus test, and mouse chromosomal aberration test were all negative, suggesting that the C. reinhardtii (red) did not show mutagenicity under the conditions of this experiment. In a 90-day repeated-dose oral toxicity study, the SD rats were orally administered daily doses of 2.0 g/kg BW, 4.0 g/kg BW, and 8.0 g/kg BW without exhibiting any signs or symptoms of toxicity. Therefore, the no observed adverse effect level (NOAEL) of C. reinhardtii (red) was 8.0 g/kg BW/day. This study contributes to information necessary to form a basis for safety for expanding the application range of C. reinhardtii (red) in food. Practical Application The aim of this study was to assess the safety of C. reinhardtii (red) and to expand its use in food applications. The major finding of this study is that the C. reinhardtii (red) did not show acute toxicity, subchronic toxicity and genotoxicity under the conditions of this experiment. This study contributes to information necessary to form a basis for safety for expanding the application range of C. reinhardtii (red) in food.

CAS / MDL: 117-10-2 53-96-3 67-56-1
研究领域: 毒理学 · 食品安全 · 营养学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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AQUATIC TOXICOLOGY · 2024 · IF 4.1

Chronic toxic effects of erythromycin and its photodegradation products on microalgae Chlorella pyrenoidosa

Jiping Li,Wei Li,Naisen Liu,Chenggong Du

The photodegradation products (PDPs) of antibiotics in the aquatic environment received increasing concern, but their chronic effects on microalgae remain unclear. This study initially focused on examining the acute effects of erythromycin (ERY), then explored the chronic impacts of ERY PDPs on Chlorella pyrenoidosa . ERY of 4.0 − 32 mg/L ERY notably inhibited the cell growth and chlorophyll synthesis. The determined 96 h median effective concentration of ERY to C. pyrenoidosa was 11.78 mg/L. Higher concentrations of ERY induced more serious oxidative damage, antioxidant enzymes alleviated the oxidative stress. 6 PDPs (PDP749, PDP747, PDP719, PDP715, PDP701 and PDP557) were identified in the photodegradation process of ERY. The predicted combined toxicity of PDPs increased in the first 3 h, then decreased. Chronic exposure showed a gradual decreasing inhibition on microalgae growth and chlorophyll content. The acute effect of ERY PDPs manifested as growth stimulation, but the chronic effect manifested as growth inhibition. The malonaldehyde contents decreased with the degradation time of ERY at 7, 14 and 21 d. However, the malonaldehyde contents of ERY PDPs treatments were elevated compared to those in the control group after 21 d. Risk assessment still need to consider the potential toxicity of degradation products under long-term exposure.

研究领域: 环境科学 · 毒理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Scientific Reports · 2017 ·Vol. 7 ·期 1 ·1-12 · IF 4.259

A Mechanism-based QSTR Model for Acute to Chronic Toxicity Extrapolation: A Case Study of Antibiotics on Luminous Bacteria

Wang Dali,Gu Yue,Zheng Min,Zhang Wei,Lin Zhifen,Liu Ying

The determination of the chronic toxicity is time-consumed and costly, so it’s of great interest to predict the chronic toxicity based on acute data. Current methods include the acute to chronic ratios (ACRs) and the QSTR models, both of which have some usage limitations. In this paper, the acute and chronic mixture toxicity of three types of antibiotics, namely sulfonamides, sulfonamide potentiators and tetracyclines, were determined by a bioluminescence inhibition test. A novel QSTR model was developed for predicting the chronic mixture toxicity using the acute data and docking-based descriptors. This model revealed a complex relationship between the acute and chronic toxicity, i.e. a linear correlation between the acute and chronic lg(−lgEC50)s, rather than the simple EC 50 s or −lgEC 50 s. In particular, the interaction energies (E bind ) of the chemicals with luciferase and LitR in the bacterial quorum sensing systems were introduced to represent their acute and chronic actions, respectively, regardless of their defined toxic mechanisms. Therefore, the present QSTR model can apply to the chemicals with distinct toxic mechanisms, as well as those with undefined mechanism. This study provides a novel idea for the acute to chronic toxicity extrapolation, which may benefit the environmental risk assessment on the pollutants.

研究领域: 环境科学 · 毒理学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF APPLIED TOXICOLOGY · 2015 ·Vol. 35 ·期 11 ·1415-1426 · IF 2.982

Safety assessment of aditoprim acute, subchronic toxicity and mutagenicity studies

Xu Wang,Ziqiang Tan,Yuanhu Pan,Awais Ihsan,Qianying Liu,Lingli Huang,Guyue Cheng,Dongmei Chen,Yanfei Tao,Zhenli Liu,Zonghui Yuan

Aditoprim (ADP), a new developed dihydrofolate reductase (DHFR) inhibitor, has great potential in clinical veterinary medicine because of its greater pharmacokinetic properties than structural analogs. Preclinical toxicology studies were performed to assess the safety of ADP including an acute oral toxicity test, a subchronic toxicity test and five mutagenicity tests. In the acute oral toxicity test, ADP was administered singly by oral gavage to Wistar rats and Kunming mice. The LD 50 calculated was 1400 mg kg –1 body weight (BW) day –1 in rats and 1130 mg kg –1 BW day –1 in mice. In a subchronic study, Wistar rats were administered ADP at dose levels of 0, 20, 100 and 1000 mg kg –1 diet for 90 days. Significant decreases were observed on body weight and food efficiency in the high-dose group. Treatment-related changes in clinical serum biochemistry were found in the medium- and high-dose groups. Significant increases in the relative weights of livers and kidneys in females and testis in males in the 1000 mg kg –1 diet, and significant decrease in relative weights of livers in males in the 100 mg kg –1 diet were noted. Histopathological observations revealed that the 1000 mg kg –1 ADP diet could induce lymphocytic infiltration and hepatocytic necrosis near the hepatic portal area. The genotoxicity of ADP was negative in tests, such as the bacterial reverse mutation assay, mice bone marrow erythrocyte micronucleus assay, in vitro chromosomal aberration test, in vitro cho/hgprt mammalian cell mutagenesis assay and mice testicle cells chromosome aberration. Based on the subchronic study, the no-observed-adverse-effect level for ADP was a 20 mg kg –1 diet, which is about 1.44-1.53 mg kg –1 BW day –1 in rats. Copyright © 2015 John Wiley & Sons, Ltd.

CAS / MDL: 50-32-8 62-50-0 154-42-7
研究领域: 药理学 · 毒理学 · 兽医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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International Journal of Environmental Research and Public Health · 2019 ·Vol. 16 ·期 2 ·209 · IF 2.468

Acute and Chronic Toxicity of Carbamazepine on the Release of Chitobiase, Molting, and Reproduction in Daphnia similis

Huihui Chen,Xiaohong Gu,Qingfei Zeng,Zhigang Mao

As one of the most frequently detected pharmaceutical compounds in aquatic environments, carbamazepine (CBZ) has recently been shown to cause acute and chronic toxicity in a variety of non-target aquatic organisms. However, little is known about the ecotoxicological effects it has on the molting and reproduction of crustaceans. The aim of the present work was to evaluate the acute and chronic toxic responses to CBZ in the crustaceanDaphnia similis. After acute exposure (4 days), CBZ did not cause lethal toxicity at the tested concentrations. However, CBZ did inhibit the molting and release of chitobiase at concentrations higher than 6.25 μg/L, with 96 h EC50(median effective concentration) values of 864.38 and 306.17 μg/L, respectively. The results of chronic exposure showed that the mean number of molts, size of the first brood, mean number of offspring per brood, mean number of broods per female, and total offspring per female decreased significantly with increasing CBZ concentrations. Significant effects of CBZ on the molting or fecundity inD. similiswere observed even at concentrations as low as 0.03 μg/L. In conclusion, CBZ can cause inhibition of molting, delayed reproduction, and reduced fecundity inD. similis. CBZ toxicity toD. similisdepends on the timing and duration of the exposure. Moreover, our results indicated that CBZ would act as an endocrine disrupter inD. similis, as with vertebrates (e.g., fish).Keywords:carbamazepine;molting;Daphnia similis;chitobiase;chronic toxicity;reproduction

CAS / MDL: 67-68-5 298-46-4
研究领域: 环境毒理学 · 水生生态学 · 医药污染
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMOSPHERE · 2020 · IF 5.778

Acute and chronic combined effect of polystyrene microplastics and dibutyl phthalate on the marine copepod Tigriopus japonicus

Zhaochuan Li,Hao Zhou,Yang Liu,Jingjing Zhan,Wentao Li,Kaiming Yang,Xianliang Yi

Dibutyl phthalate (DBP) is a commonly used additive in plastic products, so it may potentially coexist with microplastics (MPs) in marine environment. The ingestion of MPs might affect the accumulation of DBP in marine organisms. In this study, the marine copepod Tigriopus japonicus was applied to study the combined effect of DBP and polystyrene microplastics (mPS) on the copepod through both acute mortality tests and chronic reproduction tests. The LC 50 of DBP was 1.23 mg L −1 (95% CI: 1.11–1.35 mg L −1 ), while exposure to mPS didn’t have significant lethal effect on the copepods. Adsorption to MPs led to decreased bioavailability of DBP, resulting in decreased toxicity of DBP. In contrast to the results of acute toxicity tests , DBP didn’t affect the reproduction of the copepods at lower exposure concentrations, while mPS reduced the number of nauplii and extended the time to hatch. Similar as acute toxicity tests, antagonistic interaction was observed for mPS and DBP in chronic reproduction tests, which might be attributed to promoted aggregation of mPS at presence of DBP. Overall, antagonistic toxicity effect between the two pollutants was observed for both acute and chronic tests, but the mechanisms of the interaction between DBP and mPS were different. Results of the present study highlighted the importance of long-term exposure when evaluating the toxic effect of MPs and their combined effect with other chemicals.

研究领域: 环境科学 · 海洋生物学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF HAZARDOUS MATERIALS · 2017 · IF 6.065

Relationship between acute and chronic toxicity for prevalent organic pollutants in Vibrio fischeri based upon chemical mode of action

Xiao H. Wang,Ling Y. Fan,Shuo Wang,Yue Wang,Li C. Yan,Shan S. Zheng,Christopher J. Martyniuk,Yuan H. Zhao

Chemicals show diverse modes of action (MOAs) in aquatic organisms depending upon acute and chronic toxicity evaluations. Here, toxicity data for Vibrio fischeri involving 52 compounds for acute and chronic toxicity were used to determine the congruence of acute and chronic toxicity for assessing MOAs. Using toxic ratios, most of the compounds categorized into MOAs that included baseline, less inert or reactive compounds with acute toxicity were also categorized as baseline, less inert or reactive compounds with chronic toxicity. However, significantly different toxic effects were observed with acute and chronic toxicity for the reactive and specific-acting compounds. The acute-chronic toxic ratios were smaller and less variable for the baseline and less inert compounds, but were greater and more variable for the reactive and specific-acting compounds. Baseline and less inert compounds share same MOAs, but reactive and specific-acting compounds have different MOAs between acute and chronic toxicity. Bioconcentration processes cannot reach an equilibrium for highly hydrophilic and ionized compounds with short-term exposure, resulting in lower toxicity compared to long-term exposure. Pronounced differences for the antibiotics were not only due to the difference in bioconcentration, but also due to a predicted difference in MOAs during acute and chronic exposures.

研究领域: 环境毒理学 · 生态学
✓ 已验证 DOI PubMed 高影响因子
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LIMNOLOGY · 2018 ·Vol. 20 ·期 2 ·173-179 · IF 1.13

Impacts of benzophenone-type UV filters on cladoceran Daphnia carinata

Du Jingjing,Qv Mingxiang,Li Ke,Yin Xiaoyun,Meng Fanxiao,Yang Jingchao,Ma Chuang

The impacts of three commonly used benzophenone-type UV filters including benzophenone (BP), 2-hydroxy-4-methoxy-benzophenone (BP3), and 2-hydroxy-4-methoxy-benzophenone-5-sulfonicacid (BP4) were assayed in vitro using a cladoceran Daphnia carinata . The 24-h LC50 on D. carinata calculated for BP, BP3, and BP4 was 8.37, 2.18, and 82.27 mg l −1 , respectively. BP3 and BP4 significantly impacted on the time of D. carinata first molting at a concentration of 0.1 µg l −1 . BP4 had an inhibitory effect on D. carinata molting and BP3 had an inhibitory effect on D. carinata pregnancy at a concentration of 1 µg l −1 . Furthermore, BP4 significantly inhibited the number of D. carinata first brood per female at a concentration of 10 µg l −1 . All of the endpoints from acute and chronic toxicity demonstrated that the hydroxy group in BP3 and BP4 significantly enhanced the toxic effect compared to BP. Therefore, the toxicity of BP-type UV filters is related to their molecular structure.

CAS / MDL: 119-61-9 131-57-7
研究领域: 环境科学 · 毒理学
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DRUG DELIVERY · 2016 · IF 4.843

Immunosafety and chronic toxicity evaluation of monomethoxypoly(ethylene glycol)-b-poly(lactic acid) polymer micelles for paclitaxel delivery

Chang Li,Yan Shen,Chunmeng Sun,Nihad Cheraga,Jiasheng Tu

To investigate the physicochemical properties, immunosafety and chronic toxicity of monomethoxypoly(ethylene glycol)-b-poly(lactic acid) (mPEG-PLA), a copolymer used as a carrier for paclitaxel (PTX) delivery. The H-Nuclear Magnetic Resonance (H-NMR), dynamic light scattering and fluorescence probe technique were conducted to determine the physicochemical properties of mPEG-PLA copolymer. PTX-loaded polymeric micelles were characterized regarding their particle size, entrapment efficiency (EE), drug loading (DL), in vitro drug release and hemolysis rate. The complement activation in human serum and mast cells degranulation were performed by ELISA and RBL-2H3 cell line in vitro, respectively. The chronic toxicity study was carried out on beagle dogs. The optimized PTX-loaded mPEG-PLA (40/60) micelles showed a particle size of 37 nm and EE of 98.0% with a DL of 17.0% w/w. Transmission electron microscopy (TEM) analyses showed that mPEG-PLA (40/60) micelles have spherical shape with dense core. In vitro release study showed a sustained release for 24 h, and the hemolysis study revealed that mPEG-PLA (40/60) was a safe nanocarrier for intravenous administration. mPEG-PLA (40/60) showed a lower complement activation ability compared to mPEG-PLA (50/50) and Cremophor® EL (Cr EL). Furthermore, the chronic toxicity of PTX-loaded mPEG-PLA (40/60) micelles was significantly lower than those of mPEG-PLA (50/50) and Cr EL.

CAS / MDL: 129-00-0
研究领域: 药学 · 毒理学 · 纳米医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BULLETIN OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY · 2014 ·Vol. 93 ·期 2 ·204-208 · IF 1.216

Sublethal Toxic Effects of Nonylphenol Ethoxylate and Nonylphenol to Moina macrocopa

Hu Xue-lei,Sun Zhi-wei,Wang Jing-jing,An Min,Duan Shun-shan

The aim of this paper was to examine the sublethal toxic effects of nonylphenol ethoxylate (NP 10 EO), its primary degradation product nonylphenol (NP), and their mixture on Moina macrocopa . Chronic toxicity tests were carried out by using sublethal chemical concentrations. Results showed that all treatments reduced the survivorship, body length, and reproduction of M. macrocopa with NP being 10 %–20 % more toxic to M. macrocopa than NP 10 EO. Results also indicated that the toxic effects of NP 10 EO and NP mixture on M. macrocopa were more severe than that of any single chemical alone. At the highest concentration in this experiment, 0.337 mg L −1 NP 10 EO plus 0.0154 mg L −1 NP treatment caused the survivorship of M. macrocopa to zero, neonates number of reproductions to zero, 45.5 % reduction in the body length, and 88 % reduction in the total neonates number.

CAS / MDL: 84852-15-3
研究领域: 环境科学 · 毒理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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