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ARCHIVED - PSL Assessment Report for Aluminum Salts
- List of Figures
- List of Tables
- List of Acronyms and Abbreviations
- Synopsis
- 1. Introduction
- 2. Summary of Information Critical to Assessment of "Toxic" Under CEPA 1999
- 2.1 Identity and physical/chemical properties
- 2.2 Entry characterization
- 2.3 Exposure Characterization
- 2.4 Effects characterization
- 3. Assessment of "Toxic" Under CEPA 1999
- 3.1 CEPA 1999 64(a) and 64(b) Environment
- 3.2 CEPA 1999 64(c): Human health
- 3.3 Conclusion
- References
- Appendix A
- Appendix B
- Appendix C
Appendix C
Tables
Species, sex, Al species | Exposure Dose levels | Critical neurotoxic effects in adults (>90-day exposure studies) | LOEL or NOEL Da = administered | References |
|---|---|---|---|---|
| Rats | ||||
Male Sprague-Dawley rats (five per group) Al sulphate | Drinking water, for various periods up to 12 months One dose level: | Decrease in nitroxidergic neurons in the somatosensory cortex. | LOEL = 165 (Da) | Rodella et al. (2006) |
Wistar rats (3 age groups: 3, 10, 24 months) (20 per dose per age group) Al chloride | Drinking water, for 90 days Three dose levels: | Impaired vestibulo-ocular reflex (results not influenced by age) | LOEL = 43.1 (Da) NOEL = 21.5 (Da) | Mameli et al. (2006) |
Male Sprague-Dawley rats (six per group) Al maltolate | Drinking water, for 12 months One dose level: | Induced apoptosis in brain; Increased efficiency of monoamine oxidases; Increase in level of caspase 3 and 12 in brain. | LOEL = 1.0 (Dc) | Huh et al. (2005) |
Male Wistar rats (seven per group) Al chloride | Gavage (101 mg Al/kg bw/d), for one month, drinking water (45 mg Al/kg bw/d)for additional four months One dose level: | Impaired performance in Morris water maze; Increased expression of amyloid precursor protein and caspase 3 in hippocampus. | LOEL = 56 (Da) | Gong et al. (2005) |
Male Wistar rats (ten per group) Al chloride | Diet for four months One dose level: | Decrease in Na+/K+-ATPase activity in brain cortex synaptosomes. | LOEL = 19 (Da) | Silva et al. (2005) |
| Sprague-Dawley rats (nine per group) Al chloride | Gavage, for three months One dose level: Da: 121 mg Al/kg bw/d | Impaired performance in Morris water maze; Decrease in long-term potentiation in hippocampal slices. | LOEL = 121 (Da) | Shi-Lei et al. (2005) |
| Male rats (strain not specified) (20-40 per group) Al species not specified (indicated to be water-soluble) | Gavage, for three months One dose level: Da: 500 mg Al/kg bw/d | Impaired performance in Morris water maze; Altered synapses in hippocampus and frontal cortex. | LOEL = 500 (Da) | Jing et al. (2004) |
| Male Wistar rats (ten per group) Al nitrate | Drinking water, for eight months One dose level: | Evidence of increased lipid peroxidation in brain. | LOEL = 36 (Da) | Flora et al. (2003) |
Male Wistar rats (ten per group) Al chloride | Diet for four months One dose level: | Increase in synaptosomal membrane fluidity; Decrease in cholesterol/phospholipid ratio in synaptosomes. | LOEL = 19 (Da) | Silva et al. (2002) |
Male Lister hooded rats (11-24 per group) Al sulphate | Drinking water, for up to seven months One dose level: | Progressive working memory in water maze. | NOEL= 140 (Da) | Von Linstow Roloff et al. (2002) |
Male Sprague-Dawley rats (ten per group) Al nitrate with citrate (two dose levels) | Drinking water, for 6.5 months Two dose levels: | No effects on open field activity or on shuttle box performance (passive avoidance). | NOEL = 100 (Da) No information on base diet (see Sanchez et al. 1997) where lab chow intake is estimated up to 13 mg/kg bw/d. Dc = 113. | Domingo et al. (1996) |
Male Druckrey albino rats (40 per group) Al chloride | Drinking water, for 12 months One dose level: | Increase in lipid peroxidation in brain. | LOEL = 36 (Da) | Gupta and Shukla (1995) |
Wistar rats (6-8 per group) Al citrate | Diet for six months One dose level: | Cytoplasmic vacuolation in astrocytes and neurons. | LOEL = 50 (Dc) | Florence et al. (1994) |
| Male Druckrey albino rats (90 per exposure group; 6 to 10 animals per test group) Al chloride | Drinking water, for six months One dose level: | Reduction in spontaneous motor activity; Impaired learning (shuttle box, maze); Increase in brain lipid peroxidation; Reduction in Mg2+- and Na+K+-ATPase activities. | LOEL = 52 (Da) | Lal et al. (1993) |
Male Sprague-Dawley rats (4-6 per group) Al sulphate | Drinking water, for three months One dose level: | Decrease in levels of microtubule associated protein-2 and spectrin in hippocampus. | LOEL = 420 (Da) | Johnson et al. (1992) |
Male Sprague-Dawley rats (8-14 per group) Al chloride | Diet for 11 months One dose level: | Reduction in motor activity; Impaired learning (shuttle box). | LOEL = 50 (Da) | Commissaris et al. (1982) |
| Mice | ||||
CD mice (10 per group) Al lactate | Gavage, for three months One dose level: | Increase in acetylcholinesterase activity. | LOEL = 333 (Da) | Zatta et al. (2002) |
Swiss Webster mice (10-12 per group) Al lactate | Diet for 90 days One dose level: | Decrease in motor activity, hindlimb grip strength, and auditory and air puff startle responsiveness. | LOEL = 160 (Dc) | Golub et al. (1992) |
| Dogs | ||||
Beagle dogs (6M, 6F per dose) Acidic SALP | Diet for 6 months Three dose levels: | No difference in body weight; No ocular changes; No effect on haematological parameters; No change in organ weight. | NOEL = 90 (Da) | Katz et al. (1984) |
* Dose calculated with Health Canada's reference values for body weights and intakes (Health Canada 1994).
** Dose calculated with author's reported body weights and intakes.
Species, Al species | Exposure GD = gesta- | Critical effects in pups (or dams where indicated) | LOEL or NOEL (mg Al/kg bw/d) Da = administered dose Dc = combined dose | References | |
|---|---|---|---|---|---|
| Rats | |||||
Sprague-Dawley rats (12 per group) Al nitrate with citrate | Drinking water, during gestation and lactation Two maternal dose levels: | Biphasic effect on learning: improved performance at Da= 50 mg/kg bw/d, but no difference compared to controls at Da= 100 mg/kg bw/d; No effect on motor activity. | NOEL= 103 (Dc) | Roig et al. (2006) | |
Wistar rats (eight per group) Al chloride | Gavage, during gestation and lactation One maternal dose level: | Decrease in placental and fetal weight; Increase in number of resorptions; Increase in skeletal malformations; Increase in oxidative stress in brains of mothers/fetuses and sucklings. | LOEL = 70 (Da) | Sharma and Mishra (2006) | |
Sprague-Dawley rats (5-6 per group) Al chloride | Gavage, during lactation, pups also exposed 39 days after weaning via gavage One maternal dose level: | Increased lipid peroxidation, decrease in superoxide dismutase and catalase activity in cerebrum and cerebellum. | LOEL = 100 (Da) | Nehru and Anand (2005) | |
Sprague-Dawley rats (10-14 per group) Al nitrate with citrate | Drinking water, during gestation and lactation Two maternal dose levels: | Increase in number of days to sexual maturation. | LOEL = 53 (Dc) (females) LOEL = 103 (Dc) (males) | Colomina et al. (2005) | |
| Improved performance in learning tests (passive avoidance, water maze). | LOEL = 103 (Dc) | ||||
| Reduction in forelimb strength in males. | LOEL = 103 (Dc) NOEL = 53 (Dc) | ||||
Wistar rats (» seven pups per group) Al chloride | Drinking water, during lactation One maternal dose level: | Deficits in synaptic plasticity in dentate gyrus of hippocampus. | LOEL = 85 (Da) | Chen et al. (2002) | |
Wistar rats (4-10 per group) Al chloride | Drinking water, in three groups: gestation, lactation, and lactation and lifetime One maternal dose level: | Reduced body weight; Deficits in synaptic plasticity in dentate gyrus of hippocampus. (greatest effect in rats exposed from parturition throughout life, while prenatal exposure was associated with the least effect) | LOEL = 85 (Da) | Wang et al. (2002a) | |
Wistar rats (number not specified) Al sulphate | Drinking water, during gestation One maternal dose level: | Decrease in pup body weight; Decreased number of cells in cerebellum; Disaggregation of microtubules and neuronal death in cerebellar neuron cultures. | LOEL = 663 (Da) | Llansola et al. (1999) | |
Long Evans rats (number not specified) Al lactate | Drinking water, during gestation or prior to mating and then during gestation and lactation One maternal dose level: | Delayed expression of phosphorylated high molecular weight neurofilament protein in tracts in diencephalon; Maternal toxicity. | LOEL = 450 (Da) | Poulos et al. (1996) | |
THA rats (8-20 pups per group) Al chloride | Gavage, dams exposed one time (GD8) 2 maternal dose levels: | Maternal toxicity; Decreased pup weight; Delay in pinna detachment and eye opening in females; Delayed development of auditory startle in males. | LOEL = 183 (Da) | Misawa and Shigeta (1993) | |
Sprague-Dawley rats (15-19 dams per group) Al hydroxide with and without citrate | Gavage, during gestation One maternal dose level: | Fetal body weight reduced; Skeletal variations increased in Al hydroxide + citrate group. | LOEL = 133 (Da) | Gomez et al. (1991) | |
Wistar rats (6-9 dams per group) Al lactate | Diet during gestation One maternal dose level: | Impaired negative geotaxis; Impaired performance in suspension and locomotor coordination tests. | LOEL = 400 (Da) | Muller et al. (1990) | |
| No effects in righting or grasping reflex. | NOEL = 400 (Da) | ||||
Wistar rats (6-12 dams per group) Al chloride and Al lactate | Diet during gestation Three maternal dose levels | Al chloride: 100, 300 and 400 mg Al/kg bw/d | Impaired grasping reflex and impaired righting reflex. | LOEL = 300 (Da) NOEL = 100(Da) | Bernuzzi et al. (1989b) |
| Negative geotaxis and locomotor coordination. | LOEL = 400 (Da) NOEL = 300 (Da) | ||||
| Al lactate: 100, 200 and 400 mg Al/kg bw/d | Impaired grasping reflex. | LOEL = 100 (Da) | |||
| Impaired righting reflex. | LOEL = 200 (Da) NOEL = 100 (Da) | ||||
| Negative geotaxis. | NOEL = 400 (Da) | ||||
| Impaired locomotor coordination. | LOEL = 400 (Da) NOEL = 200 (Da) | ||||
Wistar rats (12 to 14 dams per groups) Al chloride | Diet, during gestation Two maternal dose levels: | Reduced body weight of pups; Impaired negative geotaxis. | LOEL = 160 (Da) | Bernuzzi et al. (1986) | |
Wistar rats (6-8 per group) Al chloride | Diet during gestation Two maternal dose levels: | No differences in number of live fetuses and resorbed/dead fetuses, fetal body weight and length, or in skeletal anomalies. | NOEL = 50 (Da) | McCormack et al. (1979) | |
| Mice | |||||
Swiss Webster mice (15-17 pups per dose group per sex) Al lactate Less than optimal diet--trace element reduction in lab chow based on deficiencies measured in U.S. women. | Diet during gestation and lactation, continued exposure of pups via diet for 14 days. Three maternal dose levels: | Decreased weight gain in pups; Impaired learning of maze with respect to cue utilization (females). | LOEL = 50 (Dc) NOEL = 10 (Dc) | Golub and Germann (2001b) | |
| Impaired performance in rotarod test (males). | LOEL = 100 (Dc) NOEL = 50 (Dc) | ||||
Swiss Webster mice (15-19 pups per dose group) Al lactate | Diet during gestation and lactation, continued exposure of pups via diet to PND 35 One maternal dose level: | Reduced forelimb and hindlimb grip strength; Decreased thermal sensitivity. | LOEL = 100 (Dc) | Golub et al. (2000) | |
Swiss Webster mice (six pups per dose group) Al lactate | Diet during gestation and lactation, continued from PND 21-45. One maternal dose level: | Decrease in myelin sheath width. | LOEL = 100 (Dc) | Golub and Tarara (1999) | |
Charles River CD1 mice (10-32 dams per group) Al nitrate | Gavage, dams exposed during gestation One maternal dose level: | Increased mortality of dams; Reduced fetal body weight. | LOEL = 29 (Da) | Belles et al. (1999) | |
NIH mice (seven dams per group) Al lactate | Diet, dams exposed during gestation and lactation, pups then exposed PND 21-40 One maternal dose level: | Increased phospholipid and galactolipid contents in brain myelin; Increased lipid peroxidation. | LOEL = 130 (Dc) | Verstraeten et al. (1998) | |
Swiss Webster mice and Sprague-Dawley rats (8-12 per group) Al lactate | Diet, dams exposed during gestation and lactation One maternal dose level: | Lower retention of both Mn and Fe following gavage of solutions with these elements. | LOEL = 100 (Dc) | Golub et al. (1996) | |
Swiss mice (number not specified) Al hydroxyde (with and without ascorbic acid) | Gavage, during gestation One dose level: | No differences found in body weight of dams; No malformations or developmental variations observed. | NOEL = 103.8 (Da) | Colomina et al. (1994) | |
Swiss Webster mice (12 pups per group) Al lactate | Diet, dams exposed during gestation and lactation, continued exposure of one group via diet during lifespan One maternal dose level: | Reduced auditory startle response. | LOEL = 130 (Dc) | Golub et al. (1994) | |
Swiss Webster mice (6-8 pups per group) Al lactate | Diet, dams exposed during gestation and lactation, continued exposure of one group via diet during lifespan One maternal dose level: | Effects on manganese metabolism. | LOEL = 130 (Dc) | Golub et al. (1993) | |
Swiss mice (10-13 dams per group) Al hydroxide or Al lactate | Gavage, dams exposed during gestation One maternal dose level: | Maternal toxicity; Fetal body weight reduced in Al lactate group; Increased incidence of morphological effects (cleft palate, delayed ossification of parietals) in Al lactate group. | LOEL = 57.5 (Da) | Colomina et al. (1992) | |
*Dose calculated with Health Canada's reference values for body weights and intakes (Health Canada 1994).
**Dose calculated with author's reported body weights and intakes.
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