| Organism | Compound | Test | Endpoint | Duration | Doses | Results | Reference |
| Wistar rat (50 m, 50 f) | MCPA | Oral feeding | Chronic toxicity, oncogenicity | Two years | 0, 1, 4, and 16 mg/kg-d | No oncogenicity; systemic NOEL = 4.4 mg/kg-d; LOEL 17.6 mg/kg-d | Bellet et al. [1] |
| B6C3F1 mice (50 m, 50 f) | MCPA | Oral feeding | Chronic toxicity, oncogenicity | Two years | 0, 20, 50, and 500 mg/kg | No oncogenicity; systemic NOEL in females = 3.9 mg/kg-d; LOEL = 19.5 mg/kg-d; systemic NOEL in males = 15.7 mg/kg-d; LOEL = 79.5 mg/kg-d | Bellet et al. [1] |
| Albino rat (m, f; 25 each) | MCPA | Oral feeding | Reproductive | Two generation | 0, 2.5, 7.5, and 22.5 mg/kg-d | Reproductive NOEL = 7.5 mg/kg-d; LOEL = 22.5 mg/kg-d | Bellet et al. [2] |
| Beagle dog (6 m, 6 f) | MCPA | Oral feeding | chronic toxicity | One year | 0, 0.15, 0.75, 3.75 mg/kg-d | Effects in liver and kidney; systemic NOEL = 0.15 mg/kg-d; LOEL = 0.75 mg/kg-d | Reported in US EPA, IRIS [175]; US EPA [3, 4] EC 2005 [30] |
| Fischer 344 rats | 2,4-D salt | Oral feeding | Chronic toxicity, oncogenicity | Two years | 0, 5, 75, and 150 mg/kg-d | No effects; NOEL = 5 mg/kg-d | Charles et al. [6] |
| B6C3F1 mice | 2,4-D salt | Oral feeding | Chronic toxicity, oncogenicity | Two years | 0, 5, 62.5, and 125 mg/kg-d | No effects | Charles et al. [6] |
| Fischer 344 rats (m, f, 50 each) | 2,4-D acid; salt; ester | Oral feeding | Subchronic toxicity | 13 weeks | 0, 1, 15, 100, and 300 mg/kg-d | NOEL = 15 mg/kg-d; statistically significant decreases in red cell mass, platelet count, T3, and T4 at 100 mg/kg-d | Charles et al. [7] |
| 5 beagle dogs/sex/group | 2,4-D acid; salt; ester | Oral feeding | Chronic toxicity, oncogenicity | One year | 0, 1, 5, and 10 mg/kg-d; 10 changed to 7.5 in yr 2 | NOEL = 1 mg/kg-d | Charles et al. [176] |
| Male CD-1 mice | salt; commercial formulation | Drinking water | Effect on spontaneous lymphocytic leukemia | 365 days | 0 to 50 mg/kg-d | No effects; more control mice died than 2,4-D treated mice | Blakley et al.[177] |
| Male Fischer 344 rats | salt; commercial formulation | Oral gavage | Immune function | 2x week for 4 weeks | 10 mg/kg | No impact on lymphocyte blastogenesis | Blakley et al. [178] |
| Swiss male (6 m) | 2,4-D salt; 2,4-DCP | Oral gavage; i.p. | Chromosomal aberrations in bone marrow, germ cells, and sperm cells | Three and five days | 1.7, 3.3, and 33 mg/kg | No effects at 1.7; statistically significant chromosomal aberrations in 2/3 mice at 3.3 mg/kg and the one mouse tested at 33 mg/kg | Amer and Aly [179] |
| 12 male CD1 mice per group | 2,4-D | Dermal | Bone marrow micronucleus | 1 topical application | Approximately 110, 220, and 442 ppm | No effect | Schop et al. [180] |
| 13 male CD1 mice per group | 2,4-D | Dermal | Hair follicle nuclear aberration | 1 topical application | Approximately 110, 220, and 442 ppm | 2% increase in nuclear aberrations at highest applied dose | Schop et al. [180] |
| 5 per dose per group male Han Wistar rat | 2,4-D acid; salt; ester; 4 other derivatives | Oral gavage | In vivo unscheduled DNA synthesis | One dose | 100, 400 ppm | No effects observed | Charles et al. [181] |
| Chinese hamster | 2,4-D acid; MCPA (pure compound and commercial herbicide) | Oral gavage | SCE in lymphocytes | 9 days | 100 mg/kg-d | Weak increase in SCE; not statistically significant | Linnainmaa [19] |
| Male Han Wistar rats | 2,4-D; MCPA | Oral gavage | SCE rat lymphocytes | 5 days wk for 2 weeks | 100 mg/kg-d | No increase in SCE | Mustonen et al. [153] |
| Male Han Wistar rats | 2,4-D; MCPA | Oral gavage | SCE rat lymphocytes | 5 days wk for 2 weeks | 100 mg/kg-d | Significantly increased peroxisome proliferation | Mustonen et al. [153] |
| Sprague Dawley (5 dose/group) | 2,4-D acid; MCPA (pure compound and commercial herbicide) | Oral gavage | SCE in rat lymphocytes | 10 days | 100, 200 mg/kg-d | No increase in SCE | Linnainmaa [19] |
| Mice (5 per dose) | 2,4-D acid | Single oral gavage | SCE in rat lymphocytes | 1 day | 50, 100, and 200 mg/kg-d | Statistically significant increase in SCE at 2 highest doses | Madrigal-Bujaidar et al. [182] |
| Osborne Wendel rats (25/dose/sex) | 2,4-D acid | Oral feeding | Chronic toxicity, oncogenicity | Two years | 0, 5, 125, 625, and 1250 mg/kg-d | No statistically significant effects | Hansen et al. [183] |
| Beagle dog (3/dose/sex) | 2,4-D acid | Oral feeding | Chronic toxicity, oncogenicity | Two years | 0, 10, 50, 100, and 500 mg/kg-d | No statistically significant effects | Hansen et al. [183] |
| Male Wistar Albino rats | 2,4-D acid; MCPA | Oral gavage | P450 induction | Three days | 50, 100, and 200 mg/kg | Significant increase in cytochrome P450 | Bacher and Gibson [24] |
| Male Wistar rats | 2,4-D salt; MCPA ester | Oral feeding | GST, GSH, and oxidation | 14 days | 1 mM/kg-d | Weak lipid peroxidation; increase in glutathione reductase activity; increase in glutathione peroxidase for MCPA | Hietanen et al. [184] |
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