Table 6.

In vivo animal studies.

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]