Risk assessment
Cyclaniliprole (Pesticides)
Summary
2017 Volume 5 Issue 1 Pages 29-30
Details
2017 Volume 5 Issue 1 Pages 29-30
The Food Safety Commission of Japan (FSCJ) conducted a risk assessment of cyclaniliprole (CAS No. 1031756-98-5), an anthranilamide insecticide, based on results from various studies. Major treatment-related effects of cyclaniliprole were observed on liver (increased liver weight and increased alkaline phosphatase) in dogs and on thyroid (hypertrophy of follicular epithelial cells) in rats. None of neurotoxicity, carcinogenicity, reproductive toxicity, teratogenicity, immunotoxicity and genotoxicity were observed. Based on the results from various studies, only parent cyclaniliprole was identified as the relevant substance to the residue definition for dietary risk assessment in agricultural products. The lowest no-observed-adverse-effect level (NOAEL) obtained in all the toxicity studies was 1.29 mg/kg bw/day in a one-year chronic toxicity study in dogs. FSCJ has established an acceptable daily intake (ADI) of 0.012 mg/kg bw/day, by applying a safety factor of 100 to the NOAEL. FSCJ judged it unnecessary to specify an acute reference dose (ARfD) since no adverse effects, possibly elicited by a single oral administration, was observed.
The Food Safety Commission of Japan (FSCJ) conducted a risk assessment of cyclaniliprole (CAS No. 1031756-98-5), an anthranilamide insecticide, based on results from various studies.
The data used in the assessment include the fate in animals (rats, goats and chickens), fate in plants (apples and lettuce), residues in crops, subacute toxicity (rats, mice and dogs), subacute neurotoxicity (rats), chronic toxicity (rats and dogs), carcinogenicity (rats and mice), two-generation reproductive toxicity (rats), developmental toxicity (rats and rabbits), genotoxicity, and immunotoxicity (mice).
Major treatment-related effects of cyclaniliprole were observed on liver (increased liver weight and increased alkaline phosphatase) in dogs and on thyroid (hypertrophy of follicular epithelial cells) in rats. None of neurotoxicity, carcinogenicity, reproductive toxicity, teratogenicity, immunotoxicity and genotoxicity were observed.
Based on the results from various studies, only parent cyclaniliprole was identified as the relevant substance to the residue definition for dietary risk assessment in agricultural products.
The lowest no-observed-adverse-effect level (NOAEL) obtained in all the toxicity studies was 1.29 mg/kg bw/day in a one-year chronic toxicity study in dogs. FSCJ has established an acceptable daily intake (ADI) of 0.012 mg/kg bw/day, by applying a safety factor of 100 to the NOAEL.
FSCJ judged it unnecessary to specify an acute reference dose (ARfD), since no adverse effects, possibly elicited by a single oral administration, was observed.
| Species | Study | Dose (mg/kg bw/day) |
NOAEL (mg/kg bw/day) |
LOAEL (mg/kg bw/day) |
Critical endpoints1) |
| Rat | 90-day subacute toxicity study |
0, 600, 6,000, 20,000 ppm M: 0, 39.9, 402, 1,330 F: 0, 43.3, 467, 1,590 |
M: 1,330 F: 1,590 |
M: - F: - |
F/M: No toxicological effects |
| 90-day subacute neurotoxicity study |
0, 600, 3,100, 16,000 ppm M: 0, 40, 204, 1,090 F: 0, 49, 240, 1,280 |
M: 1,090 F: 1,280 |
M: - F: - |
F/M: No toxicological effects (Not neurotoxic) |
|
| One-year chronic toxicity study | 0, 200, 2,000, 6,000, 20,000 ppm M: 0, 9.21, 89.6, 277, 955 F: 0, 11.7, 117, 358, 1,210 |
M: 955 F: 1,210 |
M: - F: - |
F/M: No toxicological effects |
|
| Two-year carcinogenicity study |
0, 200, 2,000, 6,000, 20,000 ppm M: 0, 7.93, 82.5, 249, 834 F: 0, 10.3, 103, 306, 1,040 |
M: 249 F: 1,040 |
M: 834 F: - |
M: Hypertrophy of thyroid follicular epithelial cell F: No toxicological effects (Not carcinogenic) |
|
| Two-generation reproductive toxicity study |
0, 500, 3,000, 20,000 ppm PM: 0, 34.9, 207, 1,410 PF: 0, 39.2, 228, 1,590 F1M: 0, 41.2, 245, 1,680 F1F: 0, 45.6, 274, 1,840 |
Parent: PM: 1,410 PF: 1,590 F1M: 1,680 F1F: 1,840 |
Parent: PM: - PF: - F1M: - F1F: - |
Parent F/M: No toxicological effects |
|
| Offspring: PM: 1,410 PF: 1,590 F1M: 1,680 F1F: 1,840 |
Offspring: PM: - PF: - F1M: - F1F: - |
Offspring F/M: No toxicological effects (No effect on reproduction) |
|||
| Developmental toxicity study |
0, 100, 300, 1,000 | Maternal: 1,000 Embryo/fetus: 1,000 |
Maternal: - Embryo/fetus: - |
Maternal: No toxicologi cal
effects Embryo/fetus: No toxicological effects (Not teratogenic) |
|
| Mouse | 90-day subacute toxicity study |
0, 200, 1,200, 8,000 ppm M: 0, 27, 159, 1,020 F: 0, 34, 179, 1,350 |
M: 1,020 F: 1,350 |
M: - F: - |
F/M: No toxicological effects |
| 18-month carcinogenicity study |
0, 200, 1,250, 8,000 ppm M: 0, 22.7, 140, 884 F: 0, 31.6, 186, 1,320 |
M: 884 F: 1,320 |
M: - F: - |
F/M: No toxicological effects (Not carcinogenic) |
|
| Rabbit | Developmental toxicity study |
0, 100, 300, 1,000 | Maternal: 1,000 Embryo/fetus: 1,000 |
Maternal: - Embryo/fetus: - |
Maternal: No toxicologi cal
effects Embryo/fetus: No toxicological effects (Not teratogenic) |
| Dog | 90-day subacute toxicity study |
0, 100, 1,000, 10,000 ppm M: 0, 2.68, 26.8, 266 F: 0, 2.75, 26.9, 270 |
M: 2.68 F: 26.9 |
M: 26.8 F: 270 |
F/M: Increase in ALP |
| One-year chronic toxicity study | 0, 50, 150, 1,000, 10,000 ppm M: 0, 1.29, 4.07, 27.2, 259 F: 0, 1.47, 4.20, 27.6, 288 |
M: 1.29 F: 1.47 |
M: 4.07 F: 4.20 |
F/M: Increase in ALP | |
| ADI | NOAEL: 1.29 SF: 100 ADI: 0.012 |
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| The critical study for setting ADI | One-year chronic toxicity study in dogs | ||||
M, Male; F, Female; F/M, both sexes; PM, Male in P (Parent) generation; PF, Female in P generation; F1M, Male in F1 generation; F1F, Female in F1 generation; -, LOAEL was not derived; 1), The adverse effect observed at LOAEL; ADI, Acceptable daily intake; SF, Safety factor
