Maleic acid hydrazide is utilized in agriculture despite the fact that it is known to have clastogen and mutagen properties. Maleic acid hydrazide's IC50 values were lower for all cell lines when compared to ethephon. Hep2 and HepG2 cells are the next most cytotoxic to Vero cells, after maleic acid hydrazide [3].

Oral, cutaneous, and inhalation routes of exposure to maleic acid hydrazide have modest acute toxicity [3].

Absorption, Distribution and Excretion
...After oral doses of 100 mg/kg bw, rabbits excreted 43 to 62% maleic hydrazide unchanged in urine within 48 hr.
(14)C Maleic hydrazide was administered orally to rats. After 3 days, very little (14)C activity was detected in tissues or blood and carbon dioxide accounted for only 0.2% of administered dose. Maleic hydrazide was rapidly excreted via urine unchanged (>90%) and as conjugate (6-8%).
Slowly absorbed over period of 24 hr by quackgrass. Rain within this period will reduce effectiveness. Rate of absorption is function of cell turgidity. Most effective absorption occurs when soil moisture is at field capacity and relative high humidity. Translocates more effectively downward. Once absorbed, maleic hydrazide is freely translocated to active growing points in plant. maleic hydrazide becomes fixed within the plant and is not metabolized.
In white ash and black locust seedlings, most of maleic hydrazide was translocated to leaves and stems of black locust seedlings within 1 day after treatment, but for white ash seedlings it remained in the stem tissue. After 30 days, the (14)C was concentrated in the leaves of the black locust seedlings, but only in the stem and at the injection point of white ash seedlings. Chromatography of the extracts showed no detectable metabolite in black locust seedlings, but 2 metabolites were detected in the white ash seedlings.
For more Absorption, Distribution and Excretion (Complete) data for MALEIC HYDRAZIDE (10 total), please visit the HSDB record page.

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Metabolism / Metabolites
When applied to tea, Camelia sinensis, MH /(maleic hydrazine)/ was degraded to lactic acid, succinic acid, maleimide and hydrazine. Extracts of treated wheat seedlings... identified... beta-glycoside of MH. ...In presence of oxygen, MH undergoes photolysis to form succinic, maleic and nitric acid; and in absence of oxygen... succinic acid.
When applied to silver maple... and American sycamore... seedlings, maleic hydrazide translocated to all parts of the plant. In the plant tissue, a metabolite was formed. Hydrolysis products of the metabolite indicated a conjugate of maleic hydrazide and glucose. When applied to tobacco plants, (14)C maleic hydrazide was rapidly translocated to growing tissues. Translocation to roots also occurred. A small amount of (14)CO2 evolved. The major metabolite in foliar tissues was identified as the beta-D-glucoside of maleic hydrazide.
In one radio label experiment in rats, 77% of the administered radioactivity was recovered in urine within 6 days. 90% of the activity was found to be unaltered maleic hydrazide. The remainder was present as a conjugate of MH.
In rats, the urine and feces samples /collected following oral administration of 3,6-dione-labelled 14C-maleic hydrazide/ contained two peaks. Poor chromatographic separation and low levels of radiolabel in the fecal samples precluded reliable identification, but the peaks appeared to represent maleic hydrazide and possibly fumaric acid. The major peak in urine, representing 60% of the urinary radiolabel in males and 80% in females, co-chromatographed with maleic hydrazide. The minor urinary peak was initially found to co-chromatograph with maleimide, fumaric acid, or maleic diamide, depending on the solvent system, but subsequent investigation with deconjugation with a beta-glucuronidase containing sulfatase activity and HPLC showed this peak to be a maleic acid conjugate, probably a sulfate.
For more Metabolism/Metabolites (Complete) data for MALEIC HYDRAZIDE (7 total), please visit the HSDB record page.

Toxicity Data
LC50 (rat) >20,000 mg/m3

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Interactions
Pretreatment of Vicia faba root tip meristems with a nontoxic dose of either hydrazine or N,N'-diformylhydrazine prior to the administration of maleic hydrazide (MH), separated by 2 hr, resulted in a significant reduction of the yield of MH induced chromatid aberrations compared to control treatments (MH only). Pretreatment with the hydrazines induces an error free repair system which reduces MH induced damage and both hydrazines and MH appear able to induce oxidative DNA lesions.
Root tip cells of Allium cepa were exposed to maleic hydrazide (0.0003 M for 2 hr) and post-treated in G2 with caffeine (2.5 mM) and various inhibitors of DNA synthesis. No enhancement of chromosome damage was observed when caffeine was present in G2, but hydroxyurea (5 mM) or 5-fluorodeoxyuridine (1x10-7 M) potentiated the frequencies of chromosome aberrations. A slight additional incr of chromosome aberration frequencies was observed following treatment with Ara C (1x10-5 M) and excess thymidine in G2. When maleic hydrazide damaged cells were pulse treated with caffeine earlier during recovery, the yield of chromosomal aberrations was enhanced. The earlier caffeine was present following maleic hydrazide treatment, the stronger was the potentiation.
Conditioning treatment of Vicia faba root tip meristem cells with nickel chloride prior to challenge treatment with triethylenemelamine or maleic hydrazide triggered protective functions against both these clastogens, i.e., resulted in a significantly reduced yield of metaphases with chromatid aberrations. Protection was prevented by pretreatment with buthionine sulfoximine, an inhibitor of the synthesis of plant phytochelatins, indicating that the nickel chloride triggered phytochelatin synthesis may be involved in the protective functions induced by nickel chloride conditioning treatment. Buthionine sulfoximine (instead of nickel chloride) conditioning treatment triggered protection against maleic hydrazide but not against triethylenemelamine.
Pretreatment of Vicia faba main root meristems with ethidium bromide or nalidixic acid significantly reduced the yield of metaphases with chromatid aberrations induced by maleic hydrazide, ie, triggered clastogenic adaptation to maleic hydrazide. No such protection occurred when the alkylating agent triethylenemelamine was used for challenge treatment. The differential response of pretreated cells to maleic hydrazide on the one hand (protection) and to triethylenemelamine (no protection) on the other supports the conclusion that clastogenic adaptation is due to different inducible (repair) functions, which eventually exert protection against clastogenic impacts.

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Non-Human Toxicity Values
LD50 Rat oral >5000 mg/kg
LD50 Rabbit percutaneous >5000 mg/kg
LD50 Rat oral 5800 mg/kg bw /Maleic hydrazide, sodium salt/
LD50 Rat oral 3900 mg/kg /Maleic hydrazide, potassium salt/
For more Non-Human Toxicity Values (Complete) data for MALEIC HYDRAZIDE (7 total), please visit the HSDB record page.

[1]. The Influence of the Plant Growth Regulator Maleic Hydrazide on Egyptian Broomrape Early Developmental Stages and Its Control Efficacy in Tomato under Greenhouse and Field Conditions. Front Plant Sci. 2017;8:691. Published 2017 May 16.

[2]. Cytotoxic effects of maleic hydrazide. Mutat Res. 1978;55(1):15-30.

[3]. Cytotoxic effects of etephon and maleic hydrazide in Vero, Hep2, HepG2 cells. Drug Chem Toxicol. 2014;37(4):459-465.

Maleic hydrazide is an odorless white solid. Sinks in water. (USCG, 1999)
Maleic hydrazide is a pyridazinone.
Maleic hydrazide (MH) was introduced into agriculture in the 1950s as a major commercial herbicide and a depressant of plant growth. It is a plant growth regulator (sprout inhibitor) and herbicide, that acts by inhibiting cell division in plants. It is used to control sprouting of potatoes and onions, suckers in tobacco, and growth of weeds, grasses and trees in/along lawns, turf, ornamental plants, non-bearing citrus, utility and highway rights-of-way, airports and industrial land. Most of the maleic hydrazide used in the U.S. is applied to tobacco (86-88%), followed by potatoes (10%), It is used to control sucker growth on tobacco plants, retardation of flowering and prolongation of dormancy period.
1,2-Dihydro-3,6-pyridazinedione. A herbicide and plant growth regulator; also used to control suckering of tobacco. Its residue in food and tobacco is highly toxic, causing CNS disturbances and liver damage.

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Mechanism of Action
Maleic hydrazide inhibits mitosis in actively growing tissues of treated plants and also has profound effects on rate of respiration. ... Maleic acid ... reacts with -SH compounds ... /and/ competes with receptor sites of ... succinic dehydrogenase. ... Inhibition ... may represent site of action ... in plants.

C4H4N2O2

112.09

112.027

123-33-1

Maleic hydrazide-d2;2398483-97-9

21954

White to off-white solid powder

1.5±0.1 g/cm3

477.2±25.0 °C at 760 mmHg

306-308 ºC

242.4±23.2 °C

0.0±1.2 mmHg at 25°C

1.640

-0.14

2

2

0

8

143

0

BGRDGMRNKXEXQD-UHFFFAOYSA-N

InChI=1S/C4H4N2O2/c7-3-1-2-4(8)6-5-3/h1-2H,(H,5,7)(H,6,8)

1,2-dihydropyridazine-3,6-dione

Maleic hydrazide Antergon Hydrazide maleique

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~125 mg/mL (~1115.18 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (18.56 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (18.56 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (18.56 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)