Zinc gluconate neutralized by arginine: what the FDA reviewed for dog products
1 Freedom of Information summary from the FDA Center for Veterinary Medicine for products containing Zinc gluconate neutralized by arginine, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- Zeuterin™ (NADA/ANADA 141-217)
Zeuterin™ NADA 141-217, Original approval, March 17, 2003; sponsor Ark Sciences, Inc.; species: Dogs; foi_id 748; FDA PDF
Indication
Chemical sterilization in 3 to 10 month old male dogs
Dose regimen
0.2 to 1.0 mL per testicle (2.6 to 13.1 mg zinc) by testicular width: 10-12 mm 0.2 mL; 13-15 mm 0.3 mL; 16-18 mm 0.5 mL; 19-21 mm 0.7 mL; 22-24 mm 0.8 mL; 25-27 mm 1.0 mL, Intratesticular injection, One injection per testicle (single treatment), Dose per testicle chosen from testicular width measured at its widest point with a metric (mm) caliper; each mL contains 13.1 mg zinc as zinc gluconate
One injection is administered per testicle. Dose per testicle is based on testicular width as determined by measuring each testicle at its widest point using a metric scale (mm) caliper. The dose table is illustrated in Table 1. TABLE 1 DOSE CORRESPONDING TO TESTICULAR WIDTH Dose Per Testicle Range of Testicular Width (mm) mL (mg Zinc) 10-12 0.2 2.6 13-15 0.3 3.9 16-18 0.5 6.6 19-21 0.7 9.2 22-24 0.8 10.5 25-27 1.0 13.1
Target-animal safety
dose multiples 1X, 1.5X, 2X; duration Injections on Days 0 and 14 (planned third injection on Day 28 not administered because testicles were too hard and small to inject); 2 month study with necropsy at Week 8; animals 24 male Beagle dogs, 6 months of age (four groups incl. placebo control).
Purpose: To determine the effect of zinc gluconate neutralized by arginine administered at 1X, 1.5X and 2X the recommended dose for three times the duration of treatment. e. Animals: 24 male Beagle dogs, 6 months of age, average testicular width of 15.2 mm, 16-21 lbs body weight.
| Finding | Quote |
|---|---|
| Third injection (Day 28) could not be given because treated testicles were too hard to penetrate and had decreased in size | The third injection was attem pted on Day 28 but was not administered because the testicles were too hard for the needle to penetrate and the decreased testicular size made injection difficult. |
| No effect on body weight, body temperature, complete blood counts, serum chemistries or gross pathology | Zinc gluconate neutralized by arginine had no effect on bod y weight, body temperature, complete blood counts, serum chemistries, and gross pathology. |
| Transient testicular swelling in all treated dogs, peaking 24-48 hours after the first injection and 24 hours after the second | All treated dogs displayed transient testicular swelling. The peak swelling occurred between 24-48 hours after the first injection and 24 hours after the second injection. |
| Dose-related seminiferous tubule atrophy (1.25% control, 65.6% 1X, 74.2% 1.5X, 80.3% 2X); testicular and epididymal weights decreased in all treated groups | Seminiferous tubules of the treated groups displayed a greater percentage of atrophy compared to the control group (1.25% in the control group, 65.6% in the 1X group, 74.2% in the 1.5X group and 80.3% in the 2X group). |
| Serious scrotal lesions (purulent discharge, necrosis) in 4 dogs, one requiring surgical castration; associated with movement during injection, pre-existing skin lesion, or injecting against resistance | More serious scrotal lesions (purulent discharge and necrosis) were seen in 4 dogs, including 1 dog that required surgical castration due to necrosis of approximately one-half of the scrotal length. |
| Adverse reactions at 1X, 1.5X and 2X: transient discomfort when sitting (all groups), swelling 24-48 h after injections (all groups), difficulty walking at 24 h after first injection (2X), scrotal pain 24 h after second injection (2X) | Zinc gluconate neutralized by arginine injected at 1X, 1.5X, and 2X the recommended dose (volume) caused the following adverse reactions: transient discomfort 14 when sitting down (all groups), swelling at 24-48 hours after the first and second injections (all groups), difficulty walking 24 hours after the first injection (2X), and scrotal pain at 24 hours after the second injection (2X). |
| Average serum testosterone lower than control in all treated groups at week 8 | The average testosterone levels for all groups treated with zinc gluconate neutralized by arginine were less than that of the control group at week 8. |
Effectiveness
Multi-site (Arizona, Florida, Missouri, New York) clinical field study with historical control (semen analyses of normal intact male dogs). 270 male dogs of various breeds, 2.5-10 months old, testicular width 10-27 mm, received a single intratesticular injection per testicle dosed by width (0.2-1.0 mL); 225 completed; dogs followed at least 6 months; n = 224 (with Month 6 semen analysis); primary endpoint: Treatment success at Month 6: aspermia, azoospermia, necrospermia or oligospermia (<20 million sperm/mL); failure: 80% progressive forward motility and >20 million sperm/mL; result: Effectiveness 99.6%: of 224 dogs, one treatment failure; 171 aspermic (76.3%), 50 azoospermic (22.3%), 1 necrospermic (0.5%), 1 oligospermic (0.5%)
Semen was collected from 224 dogs at Month 6. Based on the criteria above, the effectiveness was 99.6%. Of the 224 dogs, there was one treatment failure, 171 dogs were aspermic (76.3%), 50 were azoospermic (22.3%), 1 was necrospermic (0.5%), and 1 was oligospermic (0.5%).
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Scrotal pain (local reaction) | 17 (6.3%) | Scrotal Pain 17 6.3% | |
| Neutrophilia (general reaction) | 17 (6.3%) | Neutrophilia 17 6.3% | |
| Vomiting | 12 (4.4%) | Vomiting 12 4.4% | |
| Anorexia | 11 (4.0%) | Anorexia 11 4.0% | |
| Lethargy | 6 (2.2%) | Lethargy 6 2.2% | |
| Vocalization upon injection | 6 (2.2%) | Vocalization 6 2.2% |
Extraction notes: Original NADA 141-217 for Neutersol® (later marketed as Zeuterin™, the catalogue name). The parser did not split sections (whole body captured as 'effectiveness'), so fields were taken from the raw text. Adverse-reaction rows are field-study Table 6 (Adverse Reaction / Number of Animals (n = 270) / Percentage); denominators are the 270 injected dogs and there was no concurrent control group (historical control), so 'control' is null. Table 6 rows not captured: Kicking 1 (0.3%), Scrotal Irritation 3 (1.1%), Biting and Licking 2 (0.7%), Scrotal Swelling 2 (0.7%), Scrotal Irritation & Dermatitis 2 (0.7%), Scrotal Ulceration 1, Scrotal Infection 1, Dry Scrotal Skin 1, Scrotal Bruising 1, Preputial Swelling 1, Scrotal Sore 1 (each 0.3%), Diarrhea 5 (1.9%), Leukocytosis 2 (0.7%). Of 270 dogs injected, 225 completed (28 not returned by owners, 10 castrated, 5 died, 2 euthanized); 224 had a Month 6 semen analysis; two Month-6 successes showed increased sperm counts at Month 12. Target animal safety was a GLP study at 1X/1.5X/2X by volume (6 dogs per group, placebo = bacteriostatic water) with injections on Days 0 and 14 (Day 28 injection not feasible); doses reflected an earlier version of the dose table. Also reported but not captured as separate records: a 16-month pilot (27 Beagles, 0.2 and 0.5 mL) and a 2-year dose determination study (40 Beagles, 0.25/0.30/0.35 mL; 0.3 mL chosen for 13 mm testicle). Several quotes preserve PDF-extraction artifacts ('attem pted', 'bod y', 'Neutersol ®', embedded page number '14'). No PK data.
Reproduce: foi_structured_search(query="Zinc gluconate neutralized by arginine") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).