21. Toxicity of AuNPs in Mice.

Sr. No.	organism	method of synthesis	particle size & shape	dosage & route	exposure duration	capping/reducing agent	ζ-potential	observed toxic effect	outcome	references
1	Male albino rats	Citrate reduction	Gold nanoparticles (AuNPs): 13 ± 4 nm, spherical	570 μg/kg/day, intraperitoneal	28 days	Citrate (reducing + capping agent)		Decreased body and testicular weight, reduced testosterone, sperm count/motility, abnormal sperm morphology, histopathological changes (seminiferous tubule disruption, Sertoli and Leydig cell degeneration, mitochondrial damage)	Reversible reproductive toxicity (partial recovery at 30 days, near-complete at 60 days)
2	Mice	Citrate & NaBH4 reduction	Gold nanoparticles (AuNPs): 3–100 nm, spherical	8 mg/kg/week, intraperitoneal	21 days	Sodium citrate		Sizes 8–37 nm caused systemic toxicity (fatigue, weight loss, fur changes, spinal deformities, high mortality); histopathology revealed liver Kupffer cell proliferation, lung damage, splenic disorganization	Toxicity was size-dependent; particles <8 or >37 nm showed no adverse effects. Immunogenic peptide coating reduced toxicity
3	Mice	Citrate reduction	Gold nanoparticles (AuNPs): 2, 40, 100 nm, spherical	5 doses, intratracheal	3 weeks	Citrate	Negative	No significant toxicity; 2 nm particles showed minor liver accumulation; larger particles remained lung-localized; macrophage uptake was prominent	Translocation was size-dependent; nanoparticles were largely retained in lung macrophages with negligible systemic toxicity
4	BALB/c mice, F344 rats	Commercial	Gold nanoparticles (AuNPs): 15 nm, spherical	1000 mg/kg, intravenous, single dose	Acute	Citrate & PEG	Negative	Mice: liver granulomas, IL-18 elevation, no lethality; Rats: spleen accumulation, fecal excretion, partial mortality	Demonstrated species-specific biodistribution and immunogenicity; inflammatory but nonlethal response in mice, higher toxicity in rats
5	Wistar rats	Citrate reduction	Gold nanoparticles (AuNPs): 10, 30, 60 nm, spherical	Intravenous (dose not specified)	-	Citrate		Smaller AuNPs (10 nm) caused higher DNA damage, oxidative stress, nuclear localization; accumulation noted in liver, spleen, kidney, and intestines; inflammation and tissue injury increased with smaller size	Demonstrated size-dependent toxicity; 10 nm particles induced stronger genotoxic and inflammatory effects compared to larger ones
6	Rats	Citrate reduction	Gold nanoparticles (AuNPs): 20 nm, spherical	0.01 mg/kg, intravenous	2 months	Trisodium citrate		No overt toxicity; however, liver and spleen showed gene expression changes related to metabolism, detoxification, and immune function; minimal testis accumulation; no brain distribution	Demonstrates long-term biodistribution with subcellular, organ-specific effects without clinical toxicity
7	C57BL6/J mice	Biosynthesis (P. pterocarpum leaf extract)	Gold (b-Au-PP): 54.2 nm, spherical (hydrodynamic)	Daily, intraperitoneal (7 days)	7 days	P. pterocarpum (biocapping/reducing)	–21.1 mV	No significant hematological, biochemical, or histological toxicity; nanoparticles were stable and well-tolerated	Demonstrated excellent short-term biocompatibility; biosynthesized AuNPs show potential for biomedical applications
8	C57/Bl6 mice	Antibody conjugation	Gold (AuNPs-Cetuximab) Core: 4–5 nm; Total: ∼26 nm, spherical	90 μg Au/mouse, intravenous, single dose	Up to 6 months	Poly allylamine, Cetuximab	–7.04 mV	No acute toxicity in major organs up to 4 weeks; kidney casts and splenic apoptosis observed at 6 months	Good short-term safety profile; potential long-term organ-specific effects warrant further evaluation
9	Wistar rats	Citrate reduction	Gold (AuNPs) 10, 50, 100, 250 nm, spherical	1 mL/rat, intravenous, single dose	24 h	Citrate		No overt systemic toxicity; 10 nm particles distributed to multiple organs including brain; larger particles mostly confined to liver, spleen, and blood	Biodistribution was size-dependent; smaller particles exhibited broader organ penetration without acute toxicity
10	Mice, fibroblast cells	Chemical or green synthesis	Gold nanoparticles (AuNPs): 25–30 nm, spherical	Systemic or dermal		Phytochemicals (capping/reducing agents)		ROS production, inflammation, apoptosis, DNA damage, epigenetic alterations, cellular dysfunction	Small size, crystalline structure, and surface charge influenced toxicity; surface modification recommended to reduce toxicity
11	Male Wistar rats	Not specified; characterized by TEM and UV–vis	Gold nanoparticles (AuNPs) 5–50 nm, spherical	25–250 mg/kg, intramuscular or intravenous				Reduced testosterone, altered liver enzymes (ALT, AST, ALP), altered kidney markers (urea, creatinine), histological changes in testes, oxidative stress, hormonal disruption, cellular damage	Tissue accumulation and hormonal imbalance highlight reproductive and hepatic toxicity concerns; size and surface chemistry influenced outcomes
12	Mice	Turkevich method	BSA-coated AuNPs ∼ 20 nm, spherical	1 mg/kg, intravenous (IV)	Up to 120 days	Bovine Serum Albumin (BSA)		Accumulation in liver, spleen, kidneys; kidney inflammation; liver/spleen fibrosis; fibronectin expression; inflammatory gene upregulation	Long-term retention led to subchronic toxicity; fibrotic changes in organs noted.
13	Pc-Au NCs Study (Rats)	Green synthesis (potato extract)	Gold nanoparticles: Spherical, 12 nm (AuNPs), 20 nm (Pc-Au NCs)	10 μg/kg/day, IP	3 weeks	Phytochemicals (potato extract), Phthalocyanine	–22.7 mV (AuNPs), –19 mV (Pc-Au NCs)	No toxicity; anti-inflammatory and protective effects	Safe profile at low dose
14	Male BALB/c mice	Citrate reduction	Gold Nanoparticles: Spherical; 10 nm (GnP10), 50 nm (GnP50), 100 nm (GnP100)	4 mg/kg IV (tail vein), alone and with drugs (cisplatin, paraquat, 5-ASA)	24 h	Citric acid	Negative (due to citrate coating)	GnP10: Strong nephrotoxicity when coadministered with drugs (↑IL-6, BUN, Cr); GnP50: mild effects with 5-ASA; GnP100: no toxicity, even with drugs	Toxicity was size-dependent: smaller particles (GnP10) showed strong interaction and toxicity; larger ones (GnP100) were biocompatible even with toxic drugs
15	Male ICR mice	Turkevich method	Gold nanoparticles (AuNPs): 13.5 nm, spherical	137.5–2200 μg/kg; oral, intraperitoneal, and intravenous (tail vein) routes	14–28 days	Citrate	Not numerically stated; negative due to citrate	Low doses: no toxicity; High doses: reduced body weight, RBC count, spleen index (especially oral/IP). IV had least toxicity	Toxicity was dose- and route-dependent; tail vein was safest, supporting its use for biomedical applications
16	Male albino rats	Commercial (citrate-stabilized)	Gold nanoparticles (GNPs): 10 nm, spherical	20 μg/kg, intraperitoneal injection	7 days	Citrate	Negative (citrate buffer)	Oxidative stress, lowered antioxidants (SOD, GST), decreased neurotransmitters, brain inflammation and damage	Sulforaphane reversed toxic effects by boosting Nrf2 activity, antioxidants, and neural function
17	Swiss albino mice	Sodium borohydride reduction	Thiol-PEG capped gold nanoparticles ∼4.5 nm, spherical	IV (dose not specified), single/acute exposure	Not specified (short-term)	Thiol-functionalized triethylene glycol	Not specified; improved stability	No cytotoxicity (in vitro), no histological or biochemical toxicity; distributed in liver, kidney, tumors	High safety; favorable biodistribution and nontoxic even in tumor-bearing mice at high concentrations
18	Male C57/BL6 mice	Citrate reduction (HAuCl4)	Gold nanoparticles (GNPs) ∼12.5  ±  1.7 nm, spherical	40, 200, 400 μg/kg/day, intraperitoneal injection	8 days	Sodium citrate	–53 mV	No toxicity; normal behavior, weight, serum biochemistry, hematology, histology, despite organ accumulation.	Dose-dependent bioaccumulation occurred, but no adverse effects; supports therapeutic applications.