Regulatory Toxicology Report: Zinc
Gluconate (FDA Submission Format)
1. Chemical Identity
- Substance: Zinc Gluconate
- CAS Number: 4468-02-4
- Molecular Formula: C₁₂H₂₂O₁₄Zn
- Molecular Weight: 455.7 g/mol
- Elemental Zinc Content: Approximately 14.3%
2. Summary of Nonclinical Toxicity Studies
2.1 Acute Toxicity
- Oral LD₅₀ (Mouse): >2,000 mg/kg bw
- Inhalation LC₅₀: Not established for zinc gluconate; zinc oxide data suggest low acute
inhalation toxicity.
2.2 Repeated Dose Toxicity
- Oral NOAEL (Rat, 90-day): ~30 mg/kg bw/day (elemental zinc)
- Observed Effects: GI irritation, pancreatic degeneration, hepatocellular vacuolation,
anemia
- Inhalation NOAEC (Zinc Oxide in Guinea Pig): 2.7 mg/m³ — Pulmonary inflammation and
lung function changes noted
2.3 Non-Rodent Repeat Dose Studies
Data not available specifically for zinc gluconate in non-rodent species.
3. Critical Effects
- GI irritation
- Pancreatic acinar cell degeneration
- Hepatic effects
- Hematologic alterations (anemia)
- Pulmonary effects in inhalation studies
4. Permitted Daily Exposure (PDE)
PDE calculated using ICH Q3D method:
PDE = (NOAEL × Human BW) / (F1 × F2 × F3 × F4 × F5)
= (30 mg/kg × 50 kg) / (5 × 10 × 5 × 1 × 1) = 6 mg/day (elemental zinc)
Zinc gluconate contains ~14.3% zinc → PDE = 6 / 0.143 ≈ 42 mg/day
5. Occupational Exposure Limit (OEL)
Based on zinc oxide inhalation studies:
- NOAEC: 2.7 mg/m³
- Uncertainty Factor: 10
- OEL = 2.7 / 10 = 0.27 mg/m³
6. Genotoxicity
- Ames Test: Generally negative; positive in TA98 strain without S9 at high concentrations.
- Micronucleus Assay: Positive at 12 mM; cytotoxicity at higher doses.
Conclusion: Limited genotoxicity observed at high concentrations.
7. Reproductive and Developmental Toxicity
- Low to medium zinc doses (12–120 mg/kg) improved reproductive metrics in male rats.
- High dose (240 mg/kg) caused reproductive organ damage.
- No developmental effects observed in offspring at lower doses.
8. Carcinogenicity
- No long-term in vivo carcinogenicity studies available for zinc gluconate.
- In silico prediction (LAZAR): Potential rodent carcinogen.
Conclusion: Insufficient evidence for classification; more data needed.
9. Skin Sensitization
- No specific GPMT data for zinc gluconate.
- Analogous compounds (zinc sulfate, zinc oxide): Non-sensitizing in GPMT.
Conclusion: Likely low sensitization potential.
10. References and Data Sources
- https://pubmed.ncbi.nlm.nih.gov/3540646
- https://pmc.ncbi.nlm.nih.gov/articles/PMC5288521
- https://echa.europa.eu/registration-dossier/-/registered-dossier/15015/7/5/1
- https://onlinelibrary.wiley.com/doi/10.1155/2017/5746768