Table 1. Levels relevant to toxicological evaluation of captan.
| Species | Study | Dose (mg/kg bw/day) | NOAEL (mg/kg bw/day) and critical endpoints1) |
|---|---|---|---|
| Rat | Two-year combined chronic toxicity study/carcinogenicity study | M: 0, 25, 98, 250 | M/F: 25 |
| F: 0, 25, 99, 244 | M/F: Suppressed body weight, etc. | ||
| (Not carcinogenic) | |||
| 130-week carcinogenicity study | 0, 125, 500, 2 000 ppm | M/F: 24 | |
| M/F: 0, 5, 24, 98 | M/F: Suppressed body weight | ||
| (Not carcinogenic) | |||
| Three-generation reproduction study | 0, 25, 100, 250, 500 | Parental/offspring | |
| M/F: 25 | |||
| Embryo/fetus: 250 | |||
| Parental/offspring: Suppressed body weight | |||
| Embryo/fetus: Lower body weight | |||
| (No effect on fertility) | |||
| One-generation reproduction study | 0, 6, 12.5, 25 | Parental/offspring: 25 | |
| Parental/offspring: No toxicity | |||
| (No effect on fertility) | |||
| Developmental toxicity study | 0, 18, 90, 450 | Maternal: 18 | |
| Embryo/fetus: 90 | |||
| Maternal: Suppressed body weight, etc. | |||
| Embryo/fetus: Lower body weight | |||
| (Not teratogenic) | |||
| Mouse | 26-month carcinogenicity study | 0, 6 000, 10 000, 16 000 ppm | M/F: - |
| M: 0, 599, 1 030, | M/F: Duodenal mucosal hyperplasia, etc. | ||
| 1 890 | (Carcinogenicity) | ||
| F: 0, 634, 1 080, | Observed at 6 000 ppm | ||
| 1 880 | M/F: Increased duodenal adenoma and adenocarcinoma | ||
| 22-month carcinogenicity study | 0, 100, 400, 800, | M: 123 | |
| 6 000 ppm | F: 70.4 | ||
| M: 0, 15.1, 60.9, 123, 925 | M/F: Lymphoid infiltration in the duodenum, etc. | ||
| F: 0, 17.7, 70.4, 142, 1 040 | (Carcinogenicity) | ||
| Observed at 6 000 ppm | |||
| M/F: Increased duodenal adenoma and adenocarcinoma | |||
| 80-week carcinogenicity study | 0, 8 000, 16 000 ppm | M/F: 900 | |
| M/F: 0, 900, 2 400 | M/F: Lower average body weight, etc. | ||
| (Carcinogenicity) | |||
| Observed at 16 000 ppm | |||
| M/F: Increased duodenal adenoma | |||
| Rabbit | Developmental toxicity study | 0, 6, 12, 25, 60 | Maternal: 12 |
| (the 1st study) | Embryo/fetus: 25 | ||
| Maternal: Suppressed body weight | |||
| Embryo/fetus: Lower body weight | |||
| (Not teratogenic) | |||
| Developmental toxicity study | 0, 10, 40, 60 | Maternal: 10 | |
| (the 2nd study) | Embryo/fetus: 40 | ||
| Maternal: Suppressed body weight | |||
| Embryo/fetus: Skeletal variation | |||
| (Not teratogenic) | |||
| Developmental toxicity study | 0, 10, 30, 100 | Maternal/embryo/fetus: 10 | |
| (the 3rd study) | Maternal: Suppressed body weight, etc. | ||
| Embryo/fetus: Skeletal variation | |||
| (Not teratogenic) | |||
| Hamster | Developmental toxicity study | 0, 50, 200, 400 | Maternal/embryo/fetus: 200 |
| Maternal: Increased mortality rate, etc. | |||
| Embryo/fetus: Suppressed body weight, etc. | |||
| Dog | One-year chronic toxicity study | 0, 12.5, 60.0, 300 | M/F: 300 |
| M/F: No toxicity | |||
| Monkey | Developmental toxicity study | 0, 6.25, 12.5, 25.0 | Maternal/embryo/fetus: 12.5 |
| Maternal: Miscarriage, etc. | |||
| Maternal/embryo/fetus: Death. | |||
| (Not teratogenic) | |||
| ADI (cRfD) | NOAEL: 10 | ||
| SF: 100 | |||
| ADI: 0.1 | |||
| The critical study (studies) for setting ADI | Developmental toxicity studies in rabbits (the 2nd and 3rd studies) | ||
NOAEL, No-observed-adverse-effect level; UF, Uncertainty factors; cRfD, Chronic reference dose; SF, Safety factor; ADI, Acceptable daily intake
1) The adverse effect observed at the lowest-observed-adverse-effect level (LOAEL)