Regulatory Toxicology Report: Zinc
Gluconate
1. Chemical Identity
- Name: Zinc Gluconate
- CAS Number: 4468-02-4
- Molecular Formula: C₁₂H₂₂O₁₄Zn
- Molecular Weight: 455.7 g/mol
- Elemental Zinc Content: Approximately 14.3%
2. Nonclinical Toxicity Studies
2.1 Acute Toxicity
- Oral LD₅₀ (Mouse): >2,000 mg/kg body weight (bw)
- Inhalation LC₅₀: Data specific to zinc gluconate is limited; studies on related zinc
compounds indicate low acute inhalation toxicity.
2.2 Repeated Dose Toxicity
Oral Route (Rat, 90-day study):
- NOAEL: Approximately 30 mg/kg bw/day (elemental zinc basis)
- Observed Effects at Higher Doses:
- Gastrointestinal irritation
- Pancreatic acinar cell degeneration
- Hepatocellular vacuolation
- Hematological changes (anemia)
Inhalation Route (Guinea Pig, 5-day study):
- NOAEC: 2.7 mg/m³ (ultrafine zinc oxide particles)
- Observed Effects:
- Pulmonary inflammation
- Edema
- Decreased lung function
3. Critical Effects
Based on the nonclinical studies, the following critical effects were identified:
- Gastrointestinal irritation
- Pancreatic and hepatic effects
- Hematological changes (anemia)
- Pulmonary effects (inflammation and reduced function)
4. Permitted Daily Exposure (PDE) Calculation
Using ICH Q3D guideline formula:
PDE = (NOAEL × Body Weight) / (F1 × F2 × F3 × F4 × F5)
Where:
- NOAEL = 30 mg/kg bw/day
- Body Weight = 50 kg
- F1 = 5 (species extrapolation)
- F2 = 10 (intraspecies variability)
- F3 = 5 (study duration)
- F4 = 1 (severity of effect)
- F5 = 1 (LOAEL to NOAEL adjustment)
PDE = (30 × 50) / (5 × 10 × 5 × 1 × 1) = 6 mg/day (elemental zinc)
Zinc gluconate contains ~14.3% zinc => PDE = 6 / 0.143 = ~42 mg/day (zinc gluconate)
5. Occupational Exposure Limit (OEL) Estimation
- NOAEC (from ultrafine zinc oxide): 2.7 mg/m³
- Uncertainty Factor = 10
OEL = 2.7 / 10 = 0.27 mg/m³
6. Conclusion
- Permitted Daily Exposure (Oral): Approximately 42 mg/day (zinc gluconate)
- Occupational Exposure Limit (Inhalation): Approximately 0.27 mg/m³
- Critical Effects: GI irritation, pancreatic and hepatic toxicity, hematological changes,
pulmonary effects
This assessment should be revisited with new toxicological data as available.