Table 1. Levels relevant to toxicological evaluation of glyphosate .
| Species | Study | Technical Grade No. | Dose (ppm) |
NOAEL (mg/kg bw/day) |
LOAEL (mg/kg bw/day) |
Critical endpoints (Notes) |
|---|---|---|---|---|---|---|
| Rat | 90-day toxicity study | I | 0, 1,000, 5,000, 20,000a | M: 1,270b F: 1,620b |
- | No toxicity |
| 0, 200, 2,000, 5,000, 12,500a | M: 339 F: 339 |
M: 839 F: 802 |
M/F: Reduced gain of body weight, etc | |||
| II | 0, 1,000, 5,000, 20,000a | M: 81.3 F: 90.4 |
M: 414 F: 447 |
M/F: Increased ALT, etc | ||
| III | 0, 100, 300, 1,000, 3,000c
(mg/kg bw/day) |
M: 100 F: 300 |
M: 300 F: 1,000 |
M/F: loose feces, diarrhea, etc | ||
| 0, 2,000, 10,000, 50,000a | M: 672 F: 736 |
M: 3,690 F: 3,790 |
M/F: Hepatocellular hypertrophy, etc | |||
| IV | 0, 3,000, 10,000, 30,000a | M: 168 F: 195 |
M: 569 F: 637 |
M/F: Increased cecum weight, etc | ||
| V | 0, 1,000, 10,000, 50,000a | M: 79 F: 90 |
M: 730 F: 844 |
M/F: Increased ALP, etc | ||
| 90-day neurotoxicity study |
II | 0, 2,000, 8,000, 20,000a | M: 617 F: 1,630b |
M: 1,550 F: - |
M: Reduced gain of body weight,
etc F: No toxicity (No subacute neurotoxicity) |
|
| III | 0, 2,000, 10,000, 50,000a | M: 734 F: 858 |
M: 4,090 F: 5,010 |
M/F: Diarrhea, etc (No subacute neurotoxicity) |
||
| V | 0, 1,000, 5,000, 20,000a | M: 1,500b F: 1,560b |
- | M/F: No toxicity (No subacute neurotoxicity) |
||
| One-year toxicity study | II | 0, 2,000, 8,000, 20,000a | M: 141 F: 167 |
M: 560 F: 671 |
M/F: Increased ALT/ALP, etc | |
| Two-year combined chronic toxicity/ carcinogenicity study |
I | 0, 2,000, 8,000, 20,000a | M: 362 F: 457 |
M: 940 F: 1,180 |
M: Cataract like change F: Reduced gain of body weight (Not carcinogenic) |
|
| II | 0, 2,000, 6,000, 20,000a | M: 121 F: 145 |
M: 361 F: 437 |
M/F: Increased ALP/ALT, etc (Not carcinogenic) |
||
| III | 0, 500, 4,000, 32,000a | M: 201 F: 239 |
M: 1,750 F: 2,000 |
M/F: Decreased RBC (Not carcinogenic) |
||
| IV | 0, 3,000, 10,000, 30,000a | M: 104 F: 115 |
M: 354 F: 393 |
M/F: Increased absolute cecum weight,
etc (Not carcinogenic) |
||
| V | 0, 1,500, 5,000, 15,000a | M: 1,080b F: 349 |
M: - F: 1,380 |
M: No toxicity F: Mineralization of medullary-cortical zone in the kidney (Not carcinogenic) |
||
| Rat (cont’d) |
Two-generation of reproductive toxicity study |
I | 0, 2,000, 10,000,
30,000a |
PM: 666 PF: 777 F1M: 711 F1F: 804 |
PM: 1,980 PF: 2,320 F1M: 2,230 F1F: 2,540 |
P/F1: Reduced gain of body
weight, etc (No effect on reproduction) |
| II | 0, 1,000, 3,000,
10,000a |
Parent PM: 293 PF: 1,050b F1M: 352 F1F: 1,220b Offspring PM: 293 PF: 323 F1M: 352 F1F: 371 |
Parent PM: 985 PF: - F1M: 1,160 F1F: - Offspring PM: 293 PF: 1,050 F1M: 352 F1F: 1,220 |
Parent M: Reduced gain of body weight, etc F: No toxicity Offspring M/F: Reduced gain of body weight (No effect on reproduction) |
||
| III | 0, 400, 4,000,
40,000a |
PM: 360 PF: 374 F1M: 480 F1F: 465 |
PM: 3,810 PF: 3,730 F1M: 5,040 F1F: 4,860 |
P/F1: Reduced gain of body
weight, etc (No effect on reproduction) |
||
| IV | 0, 1,200, 6,000,
30,000a |
PM: 417 PF: 485 F1M: 458 F1F: 530 |
PM: 2,150 PF: 2,530 F1M: 2,410 F1F: 2,760 |
P: Loose feces, dilated caecum,
etc F1: Dilated caecum, etc (No effect on reproduction) |
||
| V | 0, 1,500, 5,000,
15,000a |
PM: 959b PF: 1,170b F1M: 1,170b F1F: 1,380b |
PM: - PF: - F1M: - F1F: - |
P/F1: No toxicity (No effect on reproduction) |
||
| Developmental toxicity study | I | 0, 300,1,000,
3,500c (mg/kg bw/day) |
Maternal/Fetus: 1,000 |
Maternal/Fetus: 3,500 |
Maternal: Increased mortality rate,
etc Fetus: Low body weight, etc (Not teratogenic) |
|
| II | 0, 250, 500,
1,000c (mg/kg bw/day) |
Maternal/Fetus: 1,000b |
Maternal/Fetus: - |
No toxicity (Not teratogenic) |
||
| III | 0, 250, 500,
1,000c (mg/kg bw/day) |
Maternal/Fetus: 1,000b |
Maternal/Fetus: - |
No toxicity (Not teratogenic) |
||
| IV | 0, 30, 300,
1,000c (mg/kg bw/day) |
Maternal: 300 Fetus: 1,000b |
Maternal: 1,000 Fetus: - |
Maternal: Loose feces, etc Fetus: No toxicity (Not teratogenic) |
||
| V | 0, 100, 500,
1,000c (mg/kg bw/day) |
Maternal/Fetus: 1,000 |
Maternal/Fetus: - |
No toxicity (Not teratogenic) |
||
| Mouse | 90-day toxicity study | I | 0, 5,000, 10,000, 50,000a | M: 1,870 F: 2,740 |
M: 9,700 F: 14,800 |
M/F: Reduced gain of body weight |
| III | 0, 2,000, 10,000, 50,000a | M: 1,630 F: 423 |
M: 7,990 F: 1,960 |
M: Loose feces, bloody feces,
etc F: Decreased absolute/relative kidney weight |
||
| IV | 0, 5,000, 10,000, 50,000a | M: 600 F: 765 |
M: 1,220 F: 1,490 |
M/F: Increase trend in cecum weight | ||
| Two-year combined chronic toxicity/ carcinogenicity study |
II | 0, 100, 1,000, 8,000a | M: 118 F: 159 |
M: 991 F: 1,340 |
M/F: Reduced gain of body
weight (Not carcinogenic) |
|
| 18-month carcinogenicity study | I | [2 year] 0, 1,000, 5,000, 30,000a |
M: 830 F: 979 |
M: 4,930 F: 6,130 |
M/F: Reduced gain of body
weight (Not carcinogenic) |
|
| III | 0, 500,
5,000, 50,000a |
M: 685 F: 909 |
M: 7,470 F: 8,690 |
M/F: Loose feces, etc (Not carcinogenic) |
||
| IV | 0, 1,600, 8,000, 40,000a | M: 838 F: 153 |
M: 4,350 F: 787 |
M: Increased absolute/relative cecum
weight, etc F: Reduced gain of body weight, etc (Not carcinogenic) |
||
| V | 0, 500, 1,500, 5,000a | M: 810b F: 1,080b |
M: - F: - |
No toxicity (Not carcinogenic) |
||
| Rabbit | Developmental toxicity study | I | 0, 75, 175,
350c (mg/kg bw/day) |
Maternal: 75 Fetus: 350b |
Maternal: 175 Fetus: - |
Maternal: Diarrhea, loose
feces Fetus: No toxicity (Not teratogenic) |
| II | 0, 100, 175,
300c (mg/kg bw/day) |
Maternal: 100 Fetus: 175 |
Maternal: 175 Fetus: 300 |
Maternal: Reduced gain of body weight,
etc Fetus: Low body weight, etc |
||
| III | 0, 87.5, 175,
350c (mg/kg bw/day) |
Maternal/Fetus: 350 |
Maternal/Fetus: - |
No toxicity (Not teratogenic) |
||
| IV | 0, 10, 100,
300c (mg/kg bw/day) |
Maternal: 100 Fetus: 300b |
Maternal: 300 Fetus: - |
Maternal: Loose feces,
abortion/premature birth (2 cases), reduce trend in body weight
gain Fetus: No toxicity (Not teratogenic) |
||
| V | 0, 50, 200,
400c (mg/kg bw/day) |
Maternal: 200 Fetus: 400b |
Maternal: 400 Fetus: - |
Maternal: Death, diarrhea, reduced gain
of body weight, etc Fetus: No toxicity (Not teratogenic) |
||
| Dog | 90-day toxicity study | I | [6-month] 0, 10, 60, 300c (mg/kg bw/day) |
M: 300b F: 300b |
M: - F: - |
No toxicity |
| II | 0, 2,000, 10,000, 50,000a | M: 323 F: 334 |
M: 1,680 F: 1,750 |
M: Decreased Alb, TP, etc F: Increased ALP |
||
| III | 0, 30, 100,
300c (mg/kg bw/day) |
M: 100 F: 100 |
M: 300 F: 300 |
M/F: Reduce gain of body weight, etc | ||
| IV | 0, 1,600, 8,000, 40,000a | M:
1,020b F:1,010b |
M: - F: - |
No toxicity | ||
| V | 0, 30, 300,
1,000c (mg/kg bw/day) |
M: 300 F: 300 |
M: 1,000 F: 1,000 |
M/F: Loose watery feces, etc | ||
| One-year toxicity study | I | 0, 20, 100,
500c (mg/kg bw/day) |
M: 500b F: 500b |
M: - F: - |
No toxicity | |
| II | 0, 3,000, 15,000, 30,000a | M: 907b F: 448 |
M: - F: 926 |
M: No toxicity F: Reduced gain of body weight |
||
| III | 0, 30, 100,
300c (mg/kg bw/day) |
M: 100 F: 100 |
M: 300 F: 300 |
M/F: Diarrhea, bloody feces, etc | ||
| IV | 0, 1,600, 8,000, 50,000a | M: 182 F: 184 |
M: 1,200 F: 1,260 |
M/F: Loose feces, reduce trend in body weight gain, etc | ||
| V | 0, 30, 125,
500c (mg/kg bw/day) |
M: 500b F: 500b |
M: - F: - |
No toxicity | ||
| Genotoxicity | I | No evidence of genotoxicity | ||||
| II | No evidence of genotoxicity | |||||
| III | No genotoxicity relevant for human
health [Pseudo positive in in vitro chromosomal aberration test (+S9), but negative in in vivo micronucleus test up to the highest dose in accordance with OECD TG.] |
|||||
| IV | No evidence of genotoxicity | |||||
| V | No evidence of genotoxicity | |||||
M, Male; F, Female; M/F, both sexes; PM, Male in P (Parent) generation; PF, Female in P generation; F1M, Male in F1 generation; F1F, Female in F1 generation; -, No effect observed at the highest dose tested; a, Dietary administration; b, Highest dose tested; c, Gavage administration; Alb, Albumin; TP, Total protein.