Skip to main content
. Author manuscript; available in PMC: 2016 Aug 25.
Published in final edited form as: Crit Rev Toxicol. 2014 Oct;44(Suppl 4):1–80. doi: 10.3109/10408444.2014.934439

Table 6.

Animal studies on immunotoxicity of aluminum after oral administration.

Test chemical Species Study design Studied outcomes Results/Comments References
AlCl3 Young Wistar rats (male, 5 weeks old, 110–120 g.), n = 10 per group Dose: low Dose Group (LD): 64.18 mg/kg bw/day (equal to 13 mg Al/kg bw/day)
Mid Dose Group (MD): 128.36 mg/kg bw/day (equal to 26 mg Al/kg bw)
High Dose Group (HD): 256.72 mg/kg bw/day (equal to 52 mg Al/kg bw/day)
Control group: Non- treated animals
Route of exposure : Oral (assuming gavage) with drinking water
Duration of exposure : 4 months
Physical appearance, behavior, clinical signs of intoxication and mortality level (daily, during 4 months), body weight (every 10 days), levels of CD3+, CD4+, CD8 + T lymphocytes, acid non-specific activity esterase (ANAE+) in blood, interleukin-2 (IL-2) and tumor necrosis factor-a (TNF-a) in serum (at 4 months) No deaths were reported but rats were less active (no other details available)
↓ Body weight at 1, 2, 3, and 4 months (LD, MD, HD) in a time- and dose-response manner
↓ Proportion of CD3+ (LD, MD, HD) and CD4 + T lymphocyte (MD, HD) in the blood in a dose-response manner
↓ Ratio of CD4+/CD8+ (MD, HD) in a dose-response manner
↑ Proportion of CD8 + T lymphocytes (MD, HD) in a dose-response manner
↓ level of ANAE+ in the blood (LD, MD, HD) in a dose-response manner
↓ Serum level of IL-2 (LD, MD, HD) and TNF- α (MD, HD) in a dose-response manner
Comments: Details regarding administered test chemical (chemical structure, purity), pH of the administered solutions, particular method of AlCl3 administration (gavage or free access to drinking water), data on food and water consumption – not provided; limited data available regarding treatment of control animals (was it done by the same route of exposure is not clear). Observed limitations decrease utility of reported findings for hazard identification and risk assessment
Zhu et al. (2012a)
Physical appearance, behavior, clinical signs of intoxication and mortality level (daily, during 4 months), body weight (every 10 days), levels of immunoglobulin (Ig) G, IgA, IgM, IgE, complement factor (C)3, and C4 (in serum (at 4 months) No deaths were reported but rats were less active (no other details provided)
↓ Body weight at 1, 2, 3, and 4 months (LD, MD, HD) in a dose-response manner
↑ Serum IgG (HD), IgE (MD, HD) and IgA (LD, MD, HD) in a dose-response manner
↓ Serum IgM (LD, MD, HD) in a dose-response manner
↓ Serum C3 (MD, HD) and C4 (LD, MD, HD) in a dose-response manner
Zhu et al. (2011a)
Physical appearance, behavior, clinical signs of intoxication and mortality level (daily, during 4 months), body weight (every 10 days), growth index of spleen (spleen weight × 100/body weight), concentrations of Al, iron (Fe), copper (Cu), zinc (Zn), interleukin-2 (IL-2), tumor necrosis factor-a (TNF-a) in spleen (at 4 months) Rats were less active compared to the control group (no other details provided); no deaths were observed among Al-treated or control animals
↓ Body weight at 1, 2, 3, and 4 months (lG, MD, HD) in a dose-response manner
↓ Growth index of spleen (LD, MD)
↑ Al levels in spleen (LD, MD, HD) in a dose-response manner
↑ Cu level (MD, HD) in spleen in a dose-response manner
↓ Fe (MD, HD) and Zn levels (MD, HD) in spleen in a dose-response manner
↓ IL-2 (MD, HD) and TNF-a in spleen (MD, HD) in a dose-response manner
Zhu et al. (2012b)
Physical appearance, behavior, clinical signs of intoxication and mortality level (daily, during 4 months), body weight (every 10 days), levels of erythrocytes C3b receptor rate (RBC-C3bRR), erythrocytes C3b immune complex rosette rate (RBC-ICR), erythrocytes rosette forming enhancing rate (ERER) and erythrocytes rosette forming inhibitory rate (ERIR) (at 4 months) Rats were less active compared to the control group (no other details provided); no deaths were observed during the study
↓ Body weight at 1, 2, 3, and 4 months (LD, MD, HD) in a dose-response manner
↑ level of RBC-ICR in blood (LD, MD, HD) in a dose-response manner
↑ level of ERIR in blood (LD, MD, HD) in a dose-response manner
↓ level of RBC-C3 bRR in blood (LD, MD, HD) in a dose-response manner
↓ level of ERER in blood (LD, MD, HD) in a dose-response manner
Zhu et al. (2011b)
AlCl3 6H2O Albino rats (females, 180–200 g.), n = 10 dams/offspring per group Dose:
Pregnant females: 345 mg/kg-day (≈ 40 mg Al/kg-day).
Control group: not treated animals
Route of exposure: Oral (gavage) with drinking water.
Duration of exposure:
I. From gestation day (GD) 6 to lactation day (LD) 21.
II. From GD15 to LD 21.
Serum hemolysin antibody titer in dams and their offspring, diameter of skin delayed type hypersensitivity reaction 24 hours after intradermal injection of 0.5 ml of sheep red blood cells suspension in the hind food pad in both control and treated dams and their offspring, serum protein profile (concentration of total protein, total globulins (G) and globulins fractions (α, β, γ), albumin (A) and A/G ratio), histopathological examination of thymus, spleen and liver of both dams and their offspring Dams: No differences in serum total protein or protein fractions
No histopathological changes in thymus, spleen or liver of the Al- treated dams compared to control.
Offspring: ↓ Serum total globulins, albumin/globulin (A/G) ratio and δ- globulin fraction compared to the controls
↓ Lymphoid cells in both thymus cortex and medulla and spleen white pulps
↑ Hemosiderosis in the red pulps of spleen was observed in pups born from dams treated on GD6-LD21
↑ Dilatation and congestion of hepatic central vein with hepatocytes degeneration
Khalaf et al. (2008)