Review Article

A Systematic Review of Carcinogenic Outcomes and Potential Mechanisms from Exposure to 2,4-D and MCPA in the Environment

Table 6

In vivo animal studies.

OrganismCompoundTestEndpointDurationDosesResultsReference

Wistar rat (50 m, 50 f)MCPAOral feedingChronic toxicity, oncogenicityTwo years0, 1, 4, and 16 mg/kg-dNo oncogenicity; systemic NOEL = 4.4 mg/kg-d; LOEL 17.6 mg/kg-dBellet et al. [1]

B6C3F1 mice (50 m, 50 f)MCPAOral feedingChronic toxicity, oncogenicityTwo years0, 20, 50, and 500 mg/kgNo 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-dBellet et al. [1]

Albino rat (m, f; 25 each)MCPAOral feedingReproductiveTwo generation0, 2.5, 7.5, and 22.5 mg/kg-dReproductive NOEL = 7.5 mg/kg-d; LOEL = 22.5 mg/kg-dBellet et al. [2]

Beagle dog (6 m, 6 f)MCPAOral feedingchronic toxicity One year0, 0.15, 0.75, 3.75 mg/kg-dEffects in liver and kidney; systemic NOEL = 0.15 mg/kg-d; LOEL = 0.75 mg/kg-dReported in US EPA, IRIS [175]; US EPA [3, 4] EC 2005 [30]

Fischer 344 rats2,4-D saltOral feedingChronic toxicity, oncogenicityTwo years0, 5, 75, and 150 mg/kg-dNo effects; NOEL = 5 mg/kg-dCharles et al. [6]

B6C3F1 mice2,4-D saltOral feedingChronic toxicity, oncogenicityTwo years0, 5, 62.5, and 125 mg/kg-dNo effects Charles et al. [6]

Fischer 344 rats (m, f, 50 each)2,4-D acid; salt; esterOral feedingSubchronic toxicity13 weeks0, 1, 15, 100, and 300 mg/kg-dNOEL = 15 mg/kg-d; statistically significant decreases in red cell mass, platelet count, T3, and T4 at 100 mg/kg-dCharles et al. [7]

5 beagle dogs/sex/group2,4-D acid; salt; esterOral feedingChronic toxicity, oncogenicityOne year0, 1, 5, and 10 mg/kg-d; 10 changed to 7.5 in yr 2NOEL = 1 mg/kg-dCharles et al. [176]

Male CD-1 micesalt; commercial formulationDrinking waterEffect on spontaneous lymphocytic leukemia365 days0 to 50 mg/kg-dNo effects; more control mice died than 2,4-D treated miceBlakley et al.[177]

Male Fischer 344 ratssalt; commercial formulationOral gavageImmune function2x week for 4 weeks10 mg/kgNo impact on lymphocyte blastogenesisBlakley et al. [178]

Swiss male (6 m)2,4-D salt; 2,4-DCPOral gavage; i.p.Chromosomal aberrations in bone marrow, germ cells, and sperm cellsThree and five days1.7, 3.3, and 33 mg/kgNo 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/kgAmer and Aly [179]

12 male CD1 mice per group2,4-DDermalBone marrow micronucleus1 topical applicationApproximately 110, 220, and 442 ppmNo effectSchop et al. [180]

13 male CD1 mice per group2,4-DDermalHair follicle nuclear aberration1 topical applicationApproximately 110, 220, and 442 ppm2% increase in nuclear aberrations at highest applied doseSchop et al. [180]

5 per dose per group male Han Wistar rat 2,4-D acid; salt; ester; 4 other derivativesOral gavageIn vivo unscheduled DNA synthesisOne dose100, 400 ppmNo effects observedCharles et al. [181]

Chinese hamster2,4-D acid; MCPA (pure compound and commercial herbicide)Oral gavageSCE in lymphocytes9 days100 mg/kg-dWeak increase in SCE; not statistically significantLinnainmaa [19]

Male Han Wistar rats2,4-D; MCPAOral gavageSCE rat lymphocytes5 days wk for 2 weeks100 mg/kg-dNo increase in SCEMustonen et al. [153]

Male Han Wistar rats2,4-D; MCPAOral gavageSCE rat lymphocytes5 days wk for 2 weeks100 mg/kg-dSignificantly increased peroxisome proliferationMustonen et al. [153]

Sprague Dawley (5 dose/group)2,4-D acid; MCPA (pure compound and commercial herbicide)Oral gavageSCE in rat lymphocytes10 days100, 200 mg/kg-dNo increase in SCELinnainmaa [19]

Mice (5 per dose)2,4-D acidSingle oral gavageSCE in rat lymphocytes1 day50, 100, and 200 mg/kg-dStatistically significant increase in SCE at 2 highest dosesMadrigal-Bujaidar et al. [182]

Osborne Wendel rats (25/dose/sex)2,4-D acidOral feedingChronic toxicity, oncogenicityTwo years0, 5, 125, 625, and 1250 mg/kg-dNo statistically significant effectsHansen et al. [183]

Beagle dog (3/dose/sex)2,4-D acidOral feedingChronic toxicity, oncogenicityTwo years0, 10, 50, 100, and 500 mg/kg-dNo statistically significant effectsHansen et al. [183]

Male Wistar Albino rats2,4-D acid; MCPA Oral gavageP450 inductionThree days50, 100, and 200 mg/kg Significant increase in cytochrome P450Bacher and Gibson [24]

Male Wistar rats2,4-D salt; MCPA esterOral feedingGST, GSH, and oxidation14 days1 mM/kg-dWeak lipid peroxidation; increase in glutathione reductase activity; increase in glutathione peroxidase for MCPAHietanen et al. [184]