啶虫脒可降低体重并轻微影响精子发生。 [1]。啶虫脒可以降低小鼠睾酮代谢基因、nAChR亚基基因和增殖相关基因的表达[1]。啶虫脒通过降低胆固醇转化为睾酮的速率并阻止胆固醇进入间质细胞内的线粒体来破坏随后的睾酮生物合成。这些影响会导致大鼠的生殖损伤[2]。

Animal/Disease Models: Male Sprague Dawley (SD) rat [2]
Doses: 10 mg/kg, 30 mg/kg
Route of Administration: po (oral gavage); daily; continued for 35 days
Experimental Results: By affecting mitochondria in rat Leydig cells Functions and inhibits testosterone synthesis by producing cytoplasmic adenosine triphosphate.

Absorption, Distribution and Excretion
To obtain information on the absorption, distribution, excretion rate and pathway, metabolism, and pharmacokinetics of acetamiprid, this study investigated [(14)C]acetamiprid in adult Sprague-Dawley rats (males weighing 154–193 g, females weighing 134–152 g; age 5–6 weeks at the start of administration; 15 days after administration). Radiolabeled test material (chemical purity >99.9%, radiochemical purity 97.1–97.2%) was provided by the sponsor to the contract research institution. Unlabeled test material had a chemical purity greater than 99.9%. The study was conducted 15 days after oral administration of the test material. Five treatment groups (Groups I, II, III, IV, and V) were included in this study. The first three groups each contained 6 rats (3 males and 3 females), and the latter two groups each contained 10 rats (5 males and 5 females). A separate control group (Group VI) consisted of four rats (two males and two females). Rats in Groups I, II, and III were orally administered [(14)C]acetamiprid in 0.9% saline solution for 15 consecutive days at a target dose of 1.0 mg/kg body weight (bw). Rats in Groups IV and V were orally administered [(14)C]acetamiprid in 0.9% saline solution for 14 consecutive days, followed by a single oral administration of [(14)C]acetamiprid in 0.9% saline solution on day 15. The actual doses administered to all five groups ranged from 0.97 to 1.01 mg/kg body weight. The radiochemical purity of [(14)C]acetamiprid in the dose solutions was determined to be 97.9% by high-performance liquid chromatography (HPLC). The dose solutions were stable for at least 15 days under refrigeration. The specific activity of the radiolabeled dose solutions was determined to be 1.85 × 10⁺³ Bq/μg. Group 6 received only 0.9% saline. Rats in groups 1, 2, and 3 were sacrificed 1, 10, and 96 hours after continuous injection of [(14)C]acetamiprid, respectively, over 15 days. Rats in group 4 were sacrificed 96 hours after a single injection of [(14)C]acetamiprid for tissue and organ collection. Group 5 was used solely for hemophagocytic analysis. Whole blood was collected from rats in group 3 on days 1, 3, 7, and 15, approximately 1 hour after administration, to determine the concentration of [(14)C]acetamiprid in the blood. The mean concentration of [(14)C]acetamiprid in the blood of male rats ranged from 0.477 to 0.747 μg/mL, and in female rats from 0.465 to 0.698 μg/mL. Differences were observed between animals. These results indicate that the blood concentration remained stable 1 hour after administration throughout the administration period. Whole blood was collected from rats in group 5 at approximately 0.25, 0.5, 1, 2, 3, 4, 5, 7, 9, 12, 24, and 48 hours after administration to determine the concentration of [(14)C]acetamiprid in the blood. The mean peak concentration (Cmax), time to peak concentration (Tmax), absorption half-life, and area under the concentration-time curve (AUC) in male rats were 0.798 ± 0.111 μg/mL, 2.80 ± 0.637 h, 1.35 ± 0.825 h, and 8.35 ± 1.12 μg eqhr/mL, respectively. The mean values of the corresponding parameters in female rats were 0.861 ± 0.132 μg/mL, 2.81 ± 0.894 h, 1.18 ± 0.868 h, and 10.3 ± 2.90 μg eqhr/mL, respectively. The elimination half-lives in male and female rats were 4.42 ± 1.10 hours and 5.56 ± 1.93 hours, respectively. There were no significant differences in pharmacokinetic parameters between the two sexes. The Tmax values in both sexes indicated rapid absorption of acetamiprid, reaching peak plasma concentrations and potentially saturation within approximately 2-3 hours. Elimination results showed that most of the acetamiprid (53-65%) was excreted in the urine. The total excretion in urine and cage flushing fluid was 61-73%. Results also indicated rapid absorption of acetamiprid in the gastrointestinal tract (within 1 hour), with over 90% of the administered dose excreted within 1 hour. There was no significant difference in elimination between groups receiving acetamiprid for 14 consecutive days followed by a single dose of radiolabeled acetamiprid on day 15 (group IV) and those receiving radiolabeled acetamiprid for 15 consecutive days (groups I, II, and III). The levels of radioactive material excreted in the feces of female rats (22-29%) were lower than those in male rats (30-35%). Whole blood, liver, kidney, lung, pancreas, spleen, heart, brain, testes (male), ovaries (female), skeletal muscle, inguinal fat (white), hairy skin, thyroid gland, bones, adrenal glands, gastrointestinal tract and its contents, cage flushing fluid, and residual carcass were collected from each rat in groups I, II, III, and IV. All collected samples were not mixed but were preserved and analyzed separately to ensure material balance for each rat. Radioactivity was detectable at the earliest sampling point (1 hour) in all tissues collected from each rat after the last chronic administration. Radioactivity in most tissues reached its peak 1 hour after administration and then declined rapidly (groups II and III). The Tmax of [(14)C]acetamiprid in male and female rats indicates that it is rapidly absorbed, reaching maximum plasma concentration (approximately 0.8 μg/mL) in about 2-3 hours and potentially reaching saturation. The residual levels of [(14)C]acetamiprid in tissues collected 1 hour after administration confirmed the results of the pharmacokinetic analysis. The residual levels of [(14)C]acetamiprid in tissues collected 10 hours after administration (Group II) were significantly lower than those collected 1 hour after administration. The elimination half-life in both male and female rats indicated rapid elimination. The residual levels of [(14)C]acetamiprid in tissues collected 10 hours after administration confirmed the results of the pharmacokinetic study. The residual levels of [(14)C]acetamiprid observed in tissues collected 96 hours after administration (Group III) were very low compared to those collected 1 hour and 10 hours after administration. The elimination half-life in both male and female rats was between 4 and 6 hours after administration, indicating a rapid elimination rate and minimal residual levels in tissues after prolonged administration. At all sacrifice time points, the highest radioactivity levels were observed in the gastrointestinal tract, liver, and kidneys of both male and female rats. The lowest concentrations were found in bones and white adipose tissue. Compared with group IV rats, rats treated with [(14)C]acetamiprid (group III) for 15 consecutive days had higher residual levels in all tissues. Group IV rats received a single final dose of [(14)C]acetamiprid after 14 consecutive days of unlabeled acetamiprid administration. The residual levels observed in tissues of rats sacrificed 96 hours after the last administration were very low (0.01–0.1 ppm), as most of the administered dose (>90%) was excreted in urine and feces. The total radioactive recoveries in groups I, II, III, and IV ranged from 91.7% to 106%, while the recoveries in male and female rats in group V (pharmacokinetic group) were 71.7% and 85.6%, respectively. The low recovery rate in group V may be due to loss of urine samples during a series of blood collection processes. To determine the effects of single low- and high-dose administration of acetaminophen, we investigated the absorption, distribution, metabolism, and excretion of acetaminophen in rats. [Pyridine-2,6-(14)C]acetamiprid was administered intravenously or orally to five male and five female rats in groups A, B, and D at doses of 1.0, 1.0, and 50 mg/kg body weight, respectively. In group CN-B, the metabolism of [cyano-(14)C]acetamiprid was studied at a dose of 1.0 mg/kg body weight. In group A, the absorption rate was calculated through excretion rate and metabolite analysis. In groups B, D, and CN-B, blood drug concentration, tissue distribution, metabolite analysis, and excretion rate were determined. …In summary, after oral administration of acetamiprid to rats, the drug was rapidly absorbed and widely distributed in tissues via the bloodstream. Most of the radioactive material was excreted via the kidneys in the urine, and a portion was excreted via bile in the feces. The radioactive material disappeared rapidly from the rats' bodies, and no tissues suspected of accumulating the compound were found. No sex differences were observed.
This study used Sprague-Dawley cannulated rats aged approximately 10-12 weeks to investigate bile excretion. Four male and four female cannulated rats received a single dose of [(14)C]acetamiprid dissolved in 0.9% saline via intragastric cannulation. The mean doses for male and female rats were 1.02 and 1.07 mg/kg body weight, respectively. The radiochemical purity of [(14)C]acetamiprid in the administered solution was determined to be 97.1% by high-performance liquid chromatography (HPLC). One male and one female rat were given a placebo (0.9% saline, without the test substance). From 3 to 12 hours after administration, the residual level of [(14)C]acetamiprid in bile continued to increase, reaching its highest value (percentage of administered dose) in both male and female rats at 12 hours after administration. Within 48 hours, the mean recovery rate of the administered dose in bile was 19.9% ± 1.47% in male rats and 18.6% ± 0.62% in female rats. The residual amount of [(14)C]acetamiprid excreted in bile was less than 20% of the total administered dose, indicating that bile was not the primary excretion route in either male or female rats. There were no significant differences in the absorption and first-pass metabolism/presystemic elimination of the test substance between the sexes. Within 48 hours of administration, the mean drug recovery rate in feces was 6.72% ± 3.36% in male rats and 5.84% ± 0.86% in female rats. Within 48 hours of administration, the mean drug recovery rate in urine was 24.3% ± 5.22% in male rats and 36.9% ± 3.80% in female rats. The combined drug residues in urine and cage flushing fluid were 60.2% ± 5.20% and 64.4% ± 2.86% in male and female rats, respectively, representing the main drug residues and indicating that most of the administered dose was excreted in the urine. At 48 hours post-administration, the average drug recovery rate in the liver of male rats was 0.22% ± 0.13%, and in female rats it was 0.18% ± 0.18%. At 48 hours post-administration, the average drug recovery rate in the gastrointestinal tract of male rats was 0.46% ± 0.34%, and in female rats it was 0.33% ± 0.23%. These results indicate that only a very small amount of acetamiprid (<1%) was absorbed by the liver or remained in the gastrointestinal tract in both male and female rats. The total recovery rates for the three male rats were 93.2%, 92.8%, and 89.6%, respectively. The total recovery rates for the administered dose in the three female rats were 94.9%, 93.5%, and 91.2%, respectively.
In this study, a 70% wettable powder containing [(14)C]acetamiprid (97.5% purity) was applied to the skin of male CR1:CD(SD)BR rats to investigate the absorption of acetamiprid. The experimental animals arrived at approximately 8 weeks of age, weighing 176–216 g (preliminary stage) and 143–203 g (final stage). Target dose levels were 1, 10, and 100 μg/cm². Actual dose levels were 0.0136 mg/rat (1.09 μg/cm²), 0.119 mg/rat (9.53 μg/cm²), and 1.13 mg/rat (90.2 μg/cm²), respectively. The preliminary stage included two groups of four animals each to evaluate and establish the application and skin cleansing techniques for the experimental material. In the initial phase, male rats were administered [(14)C]-acetamiprid via the skin at two dose levels (0.0128 mg/rat and 1.26 mg/rat). In the formal phase, 24 rats in each of the three groups were administered [(14)C]-acetamiprid via the skin at three dose levels. Two rats in the control group received only the excipient (1% carboxymethyl cellulose aqueous solution). Urine and feces were collected from each rat. The skin at the administration site was cleaned before sacrifice. Four rats in each dose group were sacrificed at 0.5, 1, 2, 4, 10, and 24 hours; rats in the control group were sacrificed at 24 hours. Blood was collected by cardiac puncture at sacrifice. The mean total recovery of radioactive material in each treatment group ranged from 96.6% to 102%, with the majority of the radioactive material (63.9% to 87.5%) present in the skin cleansing solution. The radioactive material in the skin at the administration site accounted for 10.2% to 32.2% of the total administered amount. Radioactive material in blood, excrement, and carcass accounted for less than 6.50% of the total administered dose. Radioactive material found in blood, excreted in excrement, and remaining in the carcass were all attributed to direct skin absorption of [(14)C]acetamiprid. Within each group, the amount of radioactive material absorbed through the skin increased with prolonged exposure time. The highest absorption was detected 24 hours after administration (the longest exposure time), with dose groups of 1.09, 9.53, and 90.2 μg/cm², and absorption amounts of 4.27% (0.581 μg), 6.34% (7.54 μg), and 2.82% (31.9 μg), respectively. The sum of direct absorption and the amount of radioactive material remaining in the skin at the administration site was considered indirect absorption. The dose groups were 1.09, 9.53, and 90.2 μg/cm², with indirect absorption of 3-5 μg, 25-37 μg, and 118-197 μg, respectively. At 24 hours post-administration, the highest blood radioactivity concentration (0.001 ppm) was observed in the 1.09 μg/sq cm² dose group; at 10 and 24 hours post-administration, the blood radioactivity concentrations in the 9.53 μg/sq cm² dose group were 0.019 ppm and 0.010 ppm, respectively; and at 24 hours post-administration, the blood radioactivity concentration in the 90.2 μg/sq cm² dose group was 0.041 ppm. At lower dose levels, direct absorption of acetamiprid in rats was dose-dependent, while it appeared to saturate at the highest dose level. For more complete data on absorption, distribution, and excretion of acetamiprid (9 items in total), please visit the HSDB record page.

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Metabolism/Metabolites
This study investigated the metabolism of acetamiprid in honeybees (Apis mellifera L.). The distribution of acetamiprid and its metabolites in six biological compartments (head, thorax, abdomen, hemolymph, midgut, and rectum) was monitored over 72 hours. Honeybees were orally administered 100 μg [(14)C]-acetamiprid/kg honeybee, a dose approximately 1500 times the median lethal dose (LD50). After 72 hours, only 40% of the total radioactivity was eliminated, indicating that acetamiprid and its metabolites tend to persist in the honeybee's body. Acetamiprid rapidly distributed throughout the honeybee's body cavities and was metabolized. Following administration, radioactivity was primarily concentrated in the abdomen, followed by the rectum. After 72 hours, the highest radioactivity levels were again detected in the abdomen (approximately 20% of the ingested dose), while the lowest total radioactivity levels were detected in the hemolymph. Radioactivity in the head did not exceed 7.6% of the total ingested radioactivity. Over 50% of acetamiprid was metabolized within 30 minutes, indicating a very short half-life for the compound. In the first few hours, acetamiprid was primarily found in tissues rich in nicotinic acetylcholine receptors, such as the abdomen, thorax, and head. Of the seven metabolites detected, the major metabolites were 6-chloronicotinic acid and an unknown metabolite called U1, which was primarily found in the rectum, thorax, and head. Our results suggest that the low toxicity of acetamiprid may be related to its rapid metabolism.
Background: Neonicotinoids are a new class of insecticides that have been used globally due to their selective toxicity to arthropods and relatively low toxicity to vertebrates. Studies have shown that some neonicotinoids can cause neurodevelopmental toxicity in mammals. This study aimed to establish the relationship between oral administration of neonicotinoids and urinary excretion in humans to facilitate biosurveillance and estimate dietary intake of neonicotinoids in Japanese adults. Methods/Main Findings: Nine healthy adults were given oral microdose of deuterium-labeled neonicotinoid insecticides (acetamiprid, thiamethoxam, dinotefuran, and imidacloprid), and 24-hour urine samples were collected for four consecutive days after administration. Excretion kinetics were modeled using both one-compartment and two-compartment models, which were then validated in a microdose study of non-deuterium-labeled neonicotinoid insecticides in 12 healthy adults. Increased concentrations of labeled neonicotinoid insecticides in urine were observed after administration. Thiamethoxam was excreted unchanged within 3 days, and most of dinotefuran was excreted unchanged within 1 day. Approximately 10% of the imidacloprid dose was excreted unchanged. Most acetamiprid was metabolized to desmethylacetamiprid. Neonicotinoid insecticides were analyzed from random urine samples of 373 Japanese adults, and daily intakes were estimated. The mean daily intake of these neonicotinoid insecticides was estimated to be 0.53–3.66 μg/day. The neonicotinoid insecticide with the highest intake in the study population was fipronil, at 64.5 μg/day, less than 1% of the acceptable daily intake. Five male and five female rats were orally administered unlabeled acetamiprid once daily for 14 consecutive days, followed by a single oral administration of radiolabeled acetamiprid on day 15. Urine and feces were collected once on day 14, and then every 24 hours after administration of the [(14)C]acetamiprid dose solution until sacrifice. Metabolites were qualitatively analyzed using thin-layer chromatography with an unlabeled reference material as a standard. The unknown metabolite was identified as an IC-O glycine conjugate (IC-O-Gly) by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The main radioactive compounds in rat excrement were acetamiprid itself (male: 5.21%; female: 7.41%), the demethylated compound IM-2-1 (male: 15.48%; female: 20.39%), the nicotinic acid derivative IC-O (male: 11.12%; female: 8.01%), and the IC-O glycine conjugate IC-O-Gly (male: 10.10%; female: 10.32%). In addition, MeS-IC-O, IM-1-4, IM-2-4, IM-O, IM-1-3, and IM-2-3 were also detected, but their levels were all below 2% of the dose. Several unknown compounds were present in the urine, one of which had a maximum abundance of 1.0% in the "Other" component. It is speculated that the main metabolic pathways of acetamiprid in rats are: N-demethylation to generate IM-2-1; removal of the cyanoacetamide side chain from IM-2-1 to generate IC-O; and removal of the acetamide and IM-2-1 cyanoacetamide side chains to generate IS-1-1 and IS-2-1, respectively. ...Radioactive compounds in rat excrement were identified and quantitatively analyzed. The main compounds identified in group B were acetamiprid itself (male: 6.10%; female: 5.63%), the demethylated compound IM-2-1 (male: 19.51%; female: 19.00%), and the nicotinic acid derivative IC-O (male: 28.19%; female: 25.52%). The main compounds identified in group D were acetamiprid (male: 7.75%; female: 7.34%), IM-2-1 (male: 24.48%; female: 21.37%), and IC-O (male: 27.11%; female: 27.63%). The main compounds detected in group A were acetamiprid (male: 4.16%; female: 6.12%), IM-2-1 (male: 13.39%; female: 18.98%), and IC-O (male: 28.13%; female: 24.73%). The main compounds detected in group CN-B were acetamiprid (male: 3.98%; female: 4.51%), IM-2-1 (male: 16.95%; female: 16.56%), IS-1-1 (male: 13.15%; female: 16.45%), and IS-2-1 (male: 35.61%; female: 30.23%). IS-1-1 and IS-2-1 are believed to be produced by the side-chain cleavage of acetamiprid and IM-2-1. In addition, IC-O-Gly, MeS-IC-O, IM-1-4, IM-2-4, IM-O, IM-1-3, and IM-2-3 were detected in groups A, B, and D, but the levels of each were below 4% of the dose. The main metabolic pathway of acetaminophen in rats is as follows: first, it is converted to IM-2-1 by demethylation, and then IS-1-1 and IS-2-1 are cleaved from acetaminophen and IM-2-1, respectively, and further converted to IC-O.
For more complete metabolite/metabolite data on acetaminophen (a total of 8 metabolites), please visit the HSDB record page.

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Biological half-life
……Whole blood was collected from each rat in group V at approximately 0.25, 0.5, 1, 2, 3, 4, 5, 7, 9, 12, 24, and 48 hours to determine the concentration of [(14)C]acetaminophen in the blood. The mean peak concentration (Cmax), time to peak concentration (Tmax), absorption half-life, and area under the concentration-time curve (AUC) in male rats were 0.798 ± 0.111 μg/mL, 2.80 ± 0.637 h, 1.35 ± 0.825 h, and 8.35 ± 1.12 μg eqhr/mL, respectively. The mean values for the corresponding parameters in female rats were 0.861 ± 0.132 μg/mL, 2.81 ± 0.894 h, 1.18 ± 0.868 h, and 10.3 ± 2.90 μg eqhr/mL, respectively. The elimination half-life in male and female rats was 4.42 ± 1.10 h and 5.56 ± 1.93 h, respectively. …
After oral administration of a 1 mg/kg dose, peak plasma concentrations were reached within 2 hours in both males and females. Under these conditions, the elimination half-life is estimated to be 6 to 11 hours. After oral administration of a 50 mg/kg dose, peak plasma concentration is slightly delayed (3-7 hours), and the elimination half-life is prolonged (8 hours for men and 15 hours for women).

Toxicity Summary
Identification and Uses: Acetamiprid is a solid pesticide. Acetamiprid is a neonicotinoid insecticide used to control piercing-sucking pests on leafy vegetables, fruit vegetables, cruciferous vegetables, citrus fruits, pome fruits, grapes, cotton, and ornamental plants and flowers. Human Studies: There have been two cases of acute poisoning resulting from suicide attempts involving the ingestion of insecticides containing acetamiprid. Both patients presented with severe nausea and vomiting, muscle weakness, hypothermia, convulsions, and clinical manifestations including tachycardia, hypotension, ECG changes, hypoxia, and thirst. The patient with a higher serum acetamiprid concentration also presented with these symptoms. These symptoms are similar to some symptoms of acute organophosphate poisoning. A 79-year-old male ingested acetamiprid and sought medical attention two hours later. Upon admission, the patient's blood acetamiprid concentration was 21.1 μg/mL. He presented with altered consciousness, hypotension, nausea, vomiting, and hyperglycemia, but without typical symptoms of organophosphate poisoning such as miosis or excessive mucus secretion. In vitro experiments showed that acetamiprid significantly induced sister chromatid exchange and chromosomal aberrations in human peripheral blood lymphocytes at all concentrations and treatment times, and significantly induced micronucleus formation at concentrations of 30, 35, and 40 μg/mL. Animal experiments: Acetamiprid did not show irritation in rabbit eye and skin irritation studies; it also did not show skin sensitization in the Magnusson and Kligman maximization tests in guinea pigs. Acetamiprid was added to the diet of mice at doses of 0, 400, 800, 1600, or 3200 ppm and fed to the mice for 13 weeks. In the 3200 ppm dose group, two male and two female mice died during the study. In the 3200 ppm dose group, five female mice developed tremors. In the 800, 1600, and 3200 ppm dose groups, treatment-related increases in mean relative liver weight were observed in both male and female mice. Microscopic examination revealed centrilobular hypertrophy and adrenal cortical fat reduction in both male and female mice at the 3200 ppm dose group. Developmental toxicity was observed in rats (NOEL = 16 mg/kg/day based on skeletal variation) and rabbits (developmental NOEL = 15 mg/kg/day based on fusion of the thoracic vertebral arch and ribs in two fetuses). In rats, acetamiprid interferes with testosterone biosynthesis by reducing the rate of cholesterol conversion to testosterone and preventing cholesterol from entering the mitochondria within the interstitial cells of the testes. These effects lead to damage to the rat reproductive system. Acetamiprid is neurotoxic in rats and can induce neurodevelopmental toxicity in mice. Acetamiprid exposure interferes with the development of neural circuits required for the performance of social and anxiety-related behaviors in male mice. Under conditions with and without metabolic activation, reverse mutation tests were performed using Salmonella typhimurium strains TA100, TA1535, TA98, and TA1537, and Escherichia coli strain WP2 uvrA. The results showed that acetamiprid was negative. Ecotoxicity studies: Acetamiprid caused neuropathy in the sciatic nerve of frogs. Oral administration of acetamiprid increased the sensitivity of bees to sucrose solution antennal stimulation (1 μg/bee) and impaired long-term memory of olfactory learning (0.1 μg/bee). Thoracic administration of acetamiprid had no effect on these behavioral tests, but increased the motility activity of bees (0.1 and 0.5 μg/bee) and the water-induced proboscis extension reflex (0.1, 0.5, and 1 μg/bee). Acetamiprid had significant adverse effects on different developmental stages of Amblyseius cucumeri. Acetamiprid exposure caused oxidative stress and DNA damage in earthworms and altered the activity of antioxidant enzymes.

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Toxicity Data
LC50 (Rat) = 290 mg/m3

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Interactions
While pesticide regulation in aquatic ecosystems has traditionally been conducted separately, pesticides in surface water are often present in mixtures. This study aimed to investigate the lethality and transcriptional responses of single and mixed pesticides (iprodione, pyraclostrobin, pyraclostrobin, and acetamiprid) in zebrafish (Danio rerio). Semi-static toxicity tests showed that pyraclostrobin was the most toxic to all four life stages of zebrafish (D. rerio) (embryonic, juvenile, larval, and adult stages), followed by iprodione and pyraclostrobin. In contrast, acetamiprid showed the lowest toxicity. Most of the selected pesticides were more toxic to embryonic zebrafish than to other life stages. Binary mixtures of iprodione with pyraclostrobin or acetamiprid, as well as ternary mixtures of iprodione + pyraclostrobin with pyraclostrobin or acetamiprid, all exhibited synergistic effects. The expression of 16 genes related to apoptosis pathways, oxidative stress, innate immunity, and endocrine disruption at the mRNA level indicated that zebrafish embryos were affected by single or combined pesticides. Compared with single pesticide use, the expression changes of P53, Tnf, TRβ, Tsh, and Cyp19a were more significant after the combined use of multiple pesticides. In summary, the simultaneous presence of multiple pesticides in aquatic environments may induce enhanced toxicity and severely damage non-target organisms. This study aimed to investigate the effects of water-soluble fullerene (fullerol) nanoparticles on the in vitro genotoxicity induced by the insecticide acetamiprid. Healthy human lung cells (IMR-90) were treated with fullerol C60(OH)n (n: 18-22) alone and in combination with acetamiprid for 24 hours. Micronucleus assay, comet assay, and γ-H2AX foci formation assay were used as genotoxicity endpoints. Clonogenic assay was used to assess cytotoxicity. The highest tested concentration of fullerol (1600 μg/mL) induced 77% cell viability, while the lowest concentration (25 μg/mL) was non-cytotoxic, although acetamiprid was cytotoxic. Fullerol did not induce genotoxicity within the tested concentration range (50–1600 μg/L). On the other hand, acetamiprid (>50 μM) significantly induced micronucleus formation and double-strand and single-strand DNA breaks in IMR-90 cells. In a co-exposure study, we selected two non-cytotoxic concentrations of fullerol (50 and 200 μg/mL) and three cytotoxic concentrations of acetamiprid (100, 200, and 400 μM). The results showed that co-exposure with fullerol significantly reduced the cytotoxicity and genotoxicity of acetamiprid in IMR-90 cells. Our findings suggest that water-soluble fullerene particles have a protective effect against herbicide-induced genotoxicity. Curcumin, a molecule found in turmeric root, possesses anti-inflammatory, antioxidant, and antitumor properties and has been widely used as a herbal remedy and food additive for the treatment or prevention of neurodegenerative diseases. This study aimed to investigate the effects of curcumin on acetamiprid-induced neurobehavioral and neuropathological changes in male rats. Three groups of male Wistar rats (n=10 per group) were used: Group 1 was the control group (CTR), receiving no acetamiprid (ACE); Group 2 was the experimental group (ACE), receiving acetamiprid at 40 mg/kg body weight daily; and Group 3 (CUR) received both curcumin (100 mg/kg) and acetamiprid (40 mg/kg). Neurobehavioral assessments included ramp tests and forepaw grasping time. Curcumin (CUR) treatment significantly prevented impaired performance in neurobehavioral tests in acephate (ACE)-treated rats, indicating defects in their sensorimotor and neuromuscular responses. Furthermore, curcumin administration protected rats from acephate-induced cerebellar toxicity, such as increased acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity, decreased cell viability, oxidative stress, and increased intracellular calcium ion concentration. In summary, these results indicate that acephate treatment significantly impairs the survival of primary neurons by inducing necrosis and accompanied by oxidative stress. In addition, curcumin alleviated the histopathological changes induced by acephate. Detecting the developmental neurotoxicity (DNT) of chemicals is crucial for protecting human health. However, the DNT of many pesticides is poorly understood. Furthermore, effective in vitro systems for assessing DNT have not yet been established. This study used the rat pheochromocytoma cell line PC-12 to evaluate the neurotoxicity (DNT) of 18 commonly used pesticides from different classes, including neonicotinoids, pyrethroids, organophosphates, organochlorines, quaternary ammonium compounds, synergistic ethers in pesticides, and the insecticide DEET. We examined the growth of neurites in PC-12 cells after 5 days of co-treatment with nerve growth factor and different concentrations of pesticides. Furthermore, we examined transcriptional changes in specific genes potentially associated with DNT, such as camek2α and camek2β, gap-43, neurofilament h, tubulin α, and tubulin β. Azadirachtin, chlorpyrifos, dieldrin, and heptachlor all strongly and in a dose-dependent manner inhibited neurite growth, which was associated with the upregulation of gap-43. Neonicotinoid insecticides such as acetamiprid, thiamethoxam, imidacloprid, and thiamethoxam; pyrethroid insecticides such as lambda-cyhalothrin, deltamethrin, deltamethrin, and permethrin; fungicides such as C12-C14-alkyl(ethylbenzyl)dimethylammonium (BAC), benzalkonium chloride, and bacitracin (dimethylbenzylammonium chloride); and synergist ethers and DEET had little or no effect on neurite growth and transcriptional changes. This study confirmed the potential developmental neurotoxicity of certain insecticides and demonstrated for the first time the potential of azathioprine as a developmental neurotoxic compound. We also confirmed that neurite growth inhibition was associated with transcriptional alterations in gap-43 expression, suggesting that gap-43 expression can serve as a biomarker for detecting and preliminarily assessing the potential pathogenic neurotransmitters (DNTs) of chemicals.
Objective: Acetamiprid (ACE) is a neonicotinoid insecticide and one of the most widely used insecticides in the world. This study evaluated the effects of ACE on humoral and cellular immune responses in rodents. We also evaluated the role of curcumin in restoring abnormal immune responses after ACE treatment. Methods: Five groups of Swiss albino mice (n=5 per group) were immunized intraperitoneally with recombinant Mycobacterium tuberculosis virulence factor CFP32. One group of mice received ACE (5 mg/kg) for 61 days, while the other group received ACE combined with curcumin (100 mg/kg). Three control groups were set up: one group of mice was untreated, the second group was treated with corn oil, and the third group was treated with curcumin alone. Humoral immune responses were assessed by detecting serum anti-rCFP32 antibody concentration using ELISA. Cellular immune responses were assessed by analyzing the proliferation of spleen cells stimulated by mitogens or rCFP32 in vitro. Results: Mice treated with ACE showed a significant suppression of specific humoral immune responses, which were restored by combining ACE with curcumin. Similarly, ACE significantly reduced the proliferation level of spleen cells after non-specific or specific activation. Curcumin partially restored antigen-specific cellular immune responses. Furthermore, curcumin alone significantly inhibited the proliferative response to mitogens, confirming its anti-mitotic effect. Histological analysis showed changes in the spleen of mice exposed to ACE. Importance: In conclusion, our data suggest that ACE may be detrimental to the immune system.

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Non-human toxicity values
Rat dermal LD50 >2000 mg/kg body weight
Rat inhalation LC50 >1.15 mg/L/4 hours (nasal cavity only)
Rat (male) oral LD50 417 mg/kg
Rat (female) oral LD50 314 mg/kg
For more complete non-human toxicity data for acetamiprid (8 in total), please visit the HSDB record page.

[1]. Effect of acetamiprid on the immature murine testes. Int J Environ Health Res. 2018 Dec;28(6):683-696.

[2]. Acetamiprid inhibits testosterone synthesis by affecting the mitochondrial function and cytoplasmic adenosine triphosphate production in rat Leydig cells. Biol Reprod. 2017 Jan 1;96(1):254-265.

Acetamiprid is a carboxymidamine compound with an acetamide structure, in which the amino hydrogen atom is replaced by (6-chloropyridin-3-yl)methyl and methyl groups, and the hydrogen atom bonded to the imino nitrogen atom is replaced by a cyano group. It is a neonicotinoid insecticide, environmental pollutant, and exogenous substance. It belongs to the monochloropyridine, nitriles, and carboxymidamine classes. Its function is similar to 2-chloropyridine. Acetamiprid has been reported to be detected in Streptomyces canus, and relevant data are available.

C10H11CLN4

222.68

222.067

135410-20-7

Acetamiprid-d3;1353869-35-8

213021

White to off-white solid powder

1.2±0.1 g/cm3

352.4±52.0 °C at 760 mmHg

101-103ºC

166.9±30.7 °C

0.0±0.8 mmHg at 25°C

1.571

0.62

52.28

0

3

3

15

280

0

WCXDHFDTOYPNIE-UHFFFAOYSA-N

InChI=1S/C10H11ClN4/c1-8(14-7-12)15(2)6-9-3-4-10(11)13-5-9/h3-5H,6H2,1-2H3

N-[(6-chloropyridin-3-yl)methyl]-N'-cyano-N-methylethanimidamide

Intruder Mospilan Mospilan

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~449.10 mM)

配方 1 中的溶解度: ≥ 2.5 mg/mL (11.23 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (11.23 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (11.23 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。