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
Following oral administration of 100 mg/kg body weight to rabbits, 43% to 62% of the unchanged maleic hydrazine was excreted in the urine within 48 hours. (14)C maleic hydrazine was administered orally to rats. After 3 days, (14)C activity was extremely low in tissues or blood, with carbon dioxide accounting for only 0.2% of the administered dose. Maleic hydrazine was rapidly excreted in the urine, with both the unchanged form (>90%) and conjugates (6-8%) being excreted. Maleic hydrazine was slowly absorbed by Imperata cylindrica within 24 hours. Rainfall during this period reduced its absorption efficiency. The absorption rate depended on cell swelling. The absorption was optimal when soil moisture reached field capacity and relative humidity was high. Downward transport was more efficient. Once absorbed, maleic hydrazine was freely transported to the plant's active growth point. Maleic hydrazine was fixed within the plant and not metabolized. In ash and black locust seedlings, most maleic hydrazide was translocated to the leaves and stems of black locust seedlings within 1 day after treatment, but remained in the stem tissue of ash seedlings. After 30 days, ¹⁴C was enriched in the leaves of black locust seedlings, while it was enriched only in the stems and injection sites of ash seedlings. Chromatographic analysis of the extracts showed no metabolites detected in black locust seedlings, while two metabolites were detected in ash seedlings. For more complete data on the absorption, distribution, and excretion of maleic hydrazide (10 in total), please visit the HSDB record page. Metabolites/Metabolites When applied to tea (Camelia sinensis), maleic hydrazide (MH) is degraded to lactic acid, succinic acid, maleimide, and hydrazine. The treated wheatgrass extract…identified…a β-glycoside of maleic hydrazide. ...In the presence of oxygen, maleic hydrazide undergoes photolysis to produce succinic acid, maleic acid, and nitric acid; under anaerobic conditions... succinic acid. When applied to seedlings of Acer pentaphyllum and Platanus orientalis, maleic hydrazide is transported to various parts of the plant. In plant tissues, a metabolite is generated. The hydrolysis product of this metabolite indicates that it is a conjugate of maleic hydrazide and glucose. When applied to tobacco plants, ¹⁴C-labeled maleic hydrazide is rapidly transported to growing tissues. It is also transported to the roots. A small amount of ¹⁴CO₂ is released. The main metabolite in leaf tissues was identified as β-D-glucosinolate of maleic hydrazide. In a rat radiolabeling experiment, 77% of the applied radioactivity was recovered from urine within 6 days. Of this, 90% was unmodified maleic hydrazide. The remainder existed as a conjugate of MH. In rats, two peaks were observed in urine and fecal samples collected after oral administration of 3,6-diketone-labeled 14C-maleic hydrazide. Reliable identification was impossible due to poor chromatographic separation and low levels of the radiolabeled substance in the fecal samples, but these peaks appeared to represent maleic hydrazide, and possibly fumaric acid. The major peak in urine (representing 60% of the radiolabeled substance in male urine and 80% in female urine) was cochromatographically separated from maleic hydrazide. Initially, a smaller peak in urine was found to be cochromatographically separated from maleimide, fumaric acid, or maleic acid diamide, depending on the solvent system. However, subsequent debinding using β-glucuronidase with sulfatase activity, combined with high-performance liquid chromatography (HPLC), indicated that this peak was a maleic acid conjugate, possibly a sulfate. For more complete metabolite/metabolite data on maleic hydrazide (7 metabolites), please visit the HSDB record page.

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

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Interactions Pretreatment of broad bean root tip meristems with a non-toxic dose of hydrazine or N,N'-dicarboxyhydrazine 2 hours before maleic hydrazine (MH) administration significantly reduced MH-induced chromatid aberration rates compared to the control group (MH administration only). Hydrazine pretreatment induces a fault-free repair system, thereby reducing MH-induced damage, and both hydrazine and MH appear to induce oxidative DNA damage. Onion root tip cells were exposed to maleic hydrazine (0.0003 M, 2 h) followed by posttreatment at G2 phase with caffeine (2.5 mM) and various DNA synthesis inhibitors. No enhancement of chromosomal damage was observed when caffeine was present at G2 phase, but hydroxyurea (5 mM) or 5-fluorodeoxyuridine (1 × 10⁻⁷ M) enhanced the frequency of chromosomal aberrations. A slight increase in the frequency of chromosomal aberrations was observed after treatment with cytarabine (1×10⁻⁵ M) and excess thymidine during G2 phase. The yield of chromosomal aberrations increased when maleic hydrazine-damaged cells were pulsed with caffeine in the early recovery phase. The earlier the caffeine appeared after maleic hydrazine treatment, the stronger the enhancement. Pretreatment of broad bean root tip meristem cells with nickel chloride before challenge treatment with triethylenetriamine or maleic hydrazine induced protection against both cleavage agents, significantly reducing the yield of metaphase cells with chromatid aberrations. Pretreatment with sulfoxide imine (a phytochelatin synthesis inhibitor) prevented the protective effect, suggesting that nickel chloride-induced phytochelatin synthesis may be involved in the protective effect induced by nickel chloride pretreatment. Pretreatment with sulfoxide imine (but not nickel chloride) induced protection against maleic hydrazine but not against triethylenetriamine. Pretreatment of broad bean taproot meristems with ethidium bromide or nalidixic acid significantly reduced the yield of metaphase cells with maleic hydrazine-induced chromatid aberration, i.e., inducing adaptation to maleic hydrazine-induced chromosome breakage. This protective effect was not observed when challenged with the alkylating agent triethylene melamine. The different responses of pretreated cells to maleic hydrazine (protective effect) and triethylene melamine (no protective effect) support the conclusion that adaptation to chromosome breakage is due to different induction (repair) functions that ultimately provide protection against the effects of chromosome breakage.

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Non-human toxicity values
Oral LD50 in rats >5000 mg/kg
Dermal LD50 in rabbits >5000 mg/kg
Oral LD50 in rats 5800 mg/kg body weight/maleic hydrazide sodium salt/
Oral LD50 in rats 3900 mg/kg/maleic hydrazide potassium salt/
For more complete non-human toxicity values for maleic hydrazide (7 in 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 hydrazine is an odorless white solid that sinks in water. (US Coast Guard, 1999)
Maleic hydrazine is a pyridazinone compound.
Maleic hydrazine (MH) was introduced into agriculture in the 1950s as a major commercial herbicide and plant growth inhibitor. It is a plant growth regulator (germination inhibitor) and herbicide that works by inhibiting plant cell division. It is used to control germination in potatoes and onions, suckers in tobacco, and the growth of weeds, grasses, and trees in lawns, turf, ornamental plants, non-fruiting citrus, utility and highway right-of-way areas, airports, and industrial land. In the United States, maleic hydrazine is mostly used in tobacco (86-88%), followed by potatoes (10%). It is used to control lateral bud growth in tobacco plants, inhibit flowering, and prolong dormancy.
1,2-Dihydro-3,6-pyridazinedione. A herbicide and plant growth regulator; also used to control lateral buds in tobacco. Its residues in food and tobacco are highly toxic, causing central nervous system disorders and liver damage. Mechanism of Action Maleic hydrazide inhibits cell mitosis in the actively growing tissues of treated plants and has a significant effect on respiration rate. ...maleic acid...reacts with -SH compounds...and competes with...succinate dehydrogenase receptor sites. ...Inhibition...may represent its 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.)