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Chlorpropham

Chlorpropham, systematically named isopropyl 3-chlorophenylcarbamate and commonly abbreviated as CIPC, is a synthetic carbamate ester (C₁₀H₁₂ClNO₂) that functions as a herbicide and plant growth regulator by inhibiting cell division, root development, and photosynthesis in target plants.^[1]^[2] It has been extensively applied post-harvest to suppress sprouting in stored potatoes, thereby extending shelf life and reducing food waste, while also serving as a pre-emergence herbicide for crops including alfalfa, beans, and blueberries.^[3]^[2] Despite its effectiveness and classification by the U.S. Environmental Protection Agency as slightly toxic (Toxicity Class III), chlorpropham has faced regulatory restrictions due to detected residues on produce, potential endocrine disruption, thyroid effects, and developmental toxicity observed in studies.^[2]^[4]^[5] The European Union prohibited its use in 2020 over health and environmental risks, leading to lowered maximum residue levels, whereas it remains registered in the United States and Australia with established tolerances.^[6]^[7]^[8]

History and Development

Introduction and Early Synthesis

Chlorpropham, also known as CIPC or isopropyl 3-chlorophenylcarbamate (C₁₀H₁₂ClNO₂), is a synthetic carbamate compound classified as a herbicide and plant growth regulator.^[1] It functions primarily through inhibition of cell division in plants, targeting meristematic tissues. The compound was first synthesized via the reaction of 3-chloroaniline with isopropyl chloroformate, a standard method for preparing phenylcarbamate esters. This synthesis approach emerged in the context of post-World War II advancements in organochlorine and carbamate chemistry aimed at agricultural pest and growth control. Development of chlorpropham traces to researchers P.C. Marth and E.S. Schultz at Pittsburgh Plate and Glass Company (PPG Industries), who introduced it in 1950 as a sprout-suppressing agent for stored potatoes.^[9] Initial experiments demonstrated its efficacy in preventing tuber sprouting by disrupting mitosis, marking an early milestone in post-harvest crop protection technologies. By 1951, PPG Industries commercialized chlorpropham under trade names such as Sprout-stop, positioning it for broader application as a pre-emergence herbicide targeting germinating seeds of annual grasses and broadleaf weeds.^[10] Early adoption focused on specialty crops, with testing in onions, beans, and potatoes revealing selective weed control properties without severe phytotoxicity to established plants when applied pre-plant or early post-emergence.^[11] These trials, conducted in the early 1950s, underscored its potential in integrated weed management, though limitations in spectrum and persistence prompted refinements in formulation and application timing. Patent filings around this period secured PPG's rights, facilitating initial market entry amid growing demand for chemical alternatives to manual labor-intensive farming practices.

Commercial Adoption and Expansion

Chlorpropham, registered in the United States in 1962 as a plant growth regulator for potato sprout inhibition, saw initial commercial adoption in the post-harvest treatment of stored tubers during the mid-1950s following early research demonstrations of its efficacy in suppressing sprouting.^[12] By the early 1960s, it had become a standard tool in the U.S. potato industry for extending storage life, with applications primarily via spraying or fogging in warehouses to maintain tuber quality and minimize weight loss from respiration and decay associated with uncontrolled sprouting.^[3] In Europe, adoption accelerated through the 1960s and 1970s alongside expanding potato storage infrastructure, where chlorpropham treatments enabled year-round market supply by delaying sprouting for up to 6-9 months under controlled conditions of 4-10°C and high humidity.^[13] This period marked its integration into commercial practices for ware and seed potatoes, reducing post-harvest losses estimated at 10-20% without suppression, as sprouting triggers uneven sizing, rot susceptibility, and reduced marketable yield.^[14] Global expansion peaked in the late 20th century, with chlorpropham applied to over 70% of stored potatoes in major producing regions including North America, Europe, and parts of Asia, establishing it as the dominant suppressant for tuber crops due to its volatility allowing uniform distribution via thermal fogging systems in large-scale facilities.^[15] Empirical data from field trials confirmed its role in preserving up to 95% of tuber weight and integrity over extended storage, compared to untreated controls exhibiting 15-25% loss from sprout-induced deterioration.^[16] Adaptations such as repeated low-dose fogging (e.g., 20-40 mg/m³) optimized residue levels while sustaining efficacy, supporting economic viability by minimizing food waste in supply chains reliant on long-term holding.^[17]

Chemical Properties

Molecular Structure and Synthesis

Chlorpropham possesses the molecular formula C₁₀H₁₂ClNO₂ and is structurally the isopropyl ester of 3-chlorophenylcarbamic acid, classifying it as a phenylcarbamate.^[1] The core structure features a carbamate linkage (-NH-COO-) connecting a meta-chlorinated phenyl ring to an isopropyl group, with the chlorine substituent at the 3-position of the benzene ring.^[1] This configuration contributes to its role as a plant growth regulator through inhibition of cell division processes.^[1] Industrial synthesis of chlorpropham primarily employs the condensation of 3-chloroaniline with isopropyl chloroformate, a phosgene-derived reagent, under controlled conditions to form the carbamate ester.^[18] Alternative routes involve generating 1-chloro-3-isocyanatobenzene as an intermediate from 3-chloroaniline and phosgene, followed by reaction with isopropanol, enabling efficient large-scale production for agricultural applications.^[19] These methods prioritize yield and purity, with processes optimized for minimal byproducts and scalability to meet commercial demands exceeding tons annually.^[18] Key physicochemical properties include low water solubility, approximately 90 mg/L at 25°C, alongside high solubility in organic solvents such as acetone, alcohols, and benzene, which necessitates formulation into emulsifiable concentrates or wettable powders for practical handling and application.^[20] These solubility characteristics stem directly from the nonpolar aromatic and isopropyl moieties dominating over the polar carbamate group.^[3]

Physical Characteristics and Stability

Chlorpropham appears as a light cream-colored crystalline solid with a slight sweet ester odor and density of 1.17 g/cm³ at 24°C.^[21] Its melting point is 41.4°C, and it has a vapor pressure of 1.33 mPa at 25°C, facilitating volatilization for gaseous application in enclosed storage spaces such as potato warehouses.^[2] Under hydrolytic conditions, chlorpropham demonstrates high stability, with about 90% remaining intact after 32 days in dark, aqueous buffered solutions at pH 4, 7, and 9 held at 40°C.^[22] Thermal degradation pathways involve initial breakdown to m-chlorophenylisocyanate at lower temperatures, followed by further conversion to 3-chloroaniline as the primary metabolite.^[23] In potato storage environments, chlorpropham residues decline gradually, with concentrations dropping from approximately 15 mg/kg shortly after application to around 9 mg/kg over subsequent weeks, influenced by ventilation and handling.^[24] Persistence is temperature-dependent, as evidenced by soil half-lives of 163 days at 15°C versus 27 days at 29°C, indicating accelerated breakdown and reduced efficacy duration under warmer, humid conditions that promote hydrolysis without complete dissipation.^[25] Optimal storage temperatures below 15°C help maintain effective residue levels for months while minimizing premature degradation.^[1]

Agricultural Applications

Primary Uses in Crop Protection

Chlorpropham is predominantly deployed as a post-harvest sprout suppressant for potatoes in storage facilities, where it is applied to inhibit premature sprouting and associated quality degradation. Treatments occur via thermal fogging of emulsifiable concentrates or direct application of dust formulations, with initial target vapor concentrations in storage air typically ranging from 15 to 25 parts per million (ppm), followed by retreatments at 10 to 20 ppm if sprouting resumes after several months.^[14] Application timing aligns with post-curing phases, often 2 to 4 weeks after harvest when tubers reach 10 to 15°C, and is integrated with ventilation practices to ensure even distribution and volatilization throughout bulk or boxed storage, preventing losses estimated at 10 to 40% in weight and marketable value without suppression due to accelerated respiration and moisture evaporation.^[14] In secondary applications, chlorpropham functions as a selective pre-emergence herbicide for weed control in crops such as garlic, onions, and sugar beets, targeting annual grasses and certain broadleaf weeds before crop seedlings emerge. For onions and garlic, it is typically sprayed at rates of 2 to 4.4 liters per hectare in 500 liters of water using boom equipment, applied to prepared seedbeds shortly after planting.^[13]^[1] Similar pre-emergence protocols apply to sugar beets, often in combination with soil incorporation to enhance soil persistence and efficacy against early weeds, though specific regional dosages vary by formulation and local regulations.^[1] These herbicide uses complement integrated weed management by providing residual control without significant impact on crop establishment when timed prior to weed germination.^[8]

Mechanism of Action

Chlorpropham inhibits mitosis in meristematic tissues, particularly those of sprouting buds, by disrupting the formation of the mitotic spindle apparatus, which prevents proper chromosome segregation during cell division.^[3]^[26] This interference targets rapidly proliferating cells, halting sprout elongation without inducing necrosis or broad tissue damage at agronomic doses.^[14] The compound also suppresses RNA and protein synthesis in affected plant cells, reducing the biosynthetic capacity required for sustained growth in meristems.^[14]^[27] Concurrently, chlorpropham impairs ATP production and uncouples oxidative phosphorylation, leading to energy deficits that exacerbate mitotic arrest and limit cellular proliferation.^[28]^[27] Empirical studies on root tip meristems and potato tubers demonstrate dose-dependent effects, with low concentrations (e.g., 10^{-5} M) causing transient delays in mitotic entry that are reversible upon removal, while higher levels (e.g., 4 \times 10^{-4} M) induce prolonged inhibition and metabolic disruption.^[27]^[28] This selectivity arises from the compound's accumulation in actively dividing tissues, minimizing impact on differentiated cells with lower division rates.^[3]

Efficacy and Benefits

Effectiveness in Sprout Suppression

Chlorpropham, applied post-harvest at rates of 20-36 g active ingredient per tonne, inhibits potato sprouting by disrupting cell division in meristematic tissues, achieving 80-95% reduction in sprout development relative to untreated controls in controlled storage environments at 8-12°C.^[14] Field and storage trials across North American and Indian cultivars, such as Russet Burbank and local varieties, confirm this suppression extends dormancy by 6-9 months, preventing premature sprouting that compromises tuber quality.^[14] In comparative studies, untreated potatoes exhibited 50-70% sprouting incidence after 6 months, while chlorpropham-treated tubers showed only 5-10%, alongside 20-30% lower weight loss due to reduced metabolic activity and evapo-transpiration.^[14] Greening, associated with sprout-induced chlorophyll synthesis, was minimized by 80-90% in treated samples, preserving visual and marketable integrity without significant varietal specificity.^[14] Indian heap and pit storage trials (17-33°C) with applications of 20-30 mg/kg yielded 0-4% sprouting versus 100% in controls after 90-105 days, demonstrating efficacy even in subtropical conditions.^[29] Long-term data from trials since the 1950s validate chlorpropham's reliability, with consistent performance documented in over 50 years of peer-reviewed research across temperate and subtropical climates, including multiple applications to sustain suppression beyond initial dormancy break.^[14] Efficacy holds across diverse potato varieties, though optimal results require temperatures below 15°C to avoid diminished inhibition at higher thresholds.^[14]

Economic and Practical Advantages

Chlorpropham, commonly applied as a post-harvest sprout suppressant, enables extended storage of potatoes for up to 5-10 months under controlled conditions, thereby reducing post-harvest losses that can reach 20-30% without treatment due to sprouting and associated weight loss or quality degradation.^[30] ^[14] This preservation supports the global potato market, valued at approximately $135.8 billion in 2024, by facilitating year-round supply and minimizing waste in processing and fresh markets where long-term storage is essential for price stability and export viability.^[31] In the United States, where chlorpropham remains approved, its use has sustained efficient storage practices, preventing spoilage that could otherwise inflate costs and disrupt supply chains reliant on seasonal harvests.^[32] The compound's application costs are notably low, typically ranging from 0.14 to 0.54 Indian rupees per kilogram in storage operations, offering a favorable return on investment through avoided losses in yield and quality.^[33] Empirical assessments in regions like India demonstrate additional savings of about INR 300 (equivalent to $4.64) per metric ton in labor for manual de-sprouting, while broader industry analyses confirm reduced overall spoilage expenses relative to untreated or alternative-managed tubers.^[34] Pre-ban applications in Europe similarly yielded practical efficiencies, with chlorpropham allowing consistent sprout control at minimal expense compared to mechanical or emerging chemical substitutes, thereby optimizing resource use in commercial facilities handling millions of tons annually.^[35] These advantages extend to operational practicality, as chlorpropham's systemic action requires fewer reapplications than non-chemical methods, streamlining storage workflows and enhancing throughput in high-volume settings.^[30] By maintaining tuber integrity without excessive energy demands for cooling or ventilation adjustments, it contributes to lower infrastructural costs, particularly in temperate climates where natural dormancy is insufficient for extended holding periods.^[14] Overall, these factors have historically bolstered farmer returns by curbing discard rates and enabling market timing that aligns with demand peaks.^[36]

Toxicity and Health Effects

Acute and Chronic Toxicity in Mammals

Chlorpropham demonstrates low acute toxicity in mammalian species. The oral LD₅₀ in rats exceeds 4,200 mg/kg body weight, classifying it as practically non-toxic by this route.^[13] Dermal LD₅₀ values in rabbits surpass 2,000 mg/kg, indicating minimal skin absorption hazards.^[13] Inhalation LC₅₀ in rats is greater than 476 mg/m³ over 4 hours, with no significant respiratory effects reported at agriculturally relevant exposure concentrations.^[37] In chronic exposure scenarios, toxicity manifests primarily at elevated doses, with effects centered on hepatic and hematopoietic systems. A 2-year dietary study in rats identified a LOAEL of 24 mg/kg body weight per day, marked by increased liver enzyme activity and organ weight changes, while lower doses showed no such alterations.^[38] In dogs, a 90-day study established a NOAEL of 25 mg/kg body weight per day, beyond which mild liver hypertrophy and methemoglobinemia—linked to the metabolite 3-chloroaniline—emerged.^[39] The metabolite 3-chloroaniline exhibits greater inherent potency than the parent compound, inducing oxidative stress and anemia in isolated assays, though its systemic impact in chlorpropham-treated animals remains dose-dependent and below thresholds for acute concern in standard protocols.^[40] Overall, chronic NOAELs cluster in the 10–25 mg/kg body weight per day range across rodent and canine models, with liver effects confined to high-dose regimens exceeding practical exposure margins.^[41]

Developmental and Reproductive Studies

In prenatal developmental toxicity studies conducted in rats, oral administration of chlorpropham during organogenesis periods resulted in increased fetal resorptions and other developmental variations at doses of 500 mg/kg body weight per day or higher, establishing a no-observed-adverse-effect level (NOAEL) for developmental toxicity at 250 mg/kg/day.^[42] Malformations, such as skeletal abnormalities, were observed at even higher doses exceeding 300 mg/kg/day in some evaluations, though these were accompanied by maternal toxicity including reduced body weight gain (maternal NOAELs ranging from 50 to 200 mg/kg/day across studies).^[43] No developmental effects were reported below 200 mg/kg/day, and similar studies in rabbits confirmed low concern with NOAELs for both maternal and fetal effects above 100 mg/kg/day.^[44]^[45] Reproductive toxicity assessments in rats via multi-generational dietary studies demonstrated no impacts on fertility, gestation, or offspring viability up to the highest tested concentration of 10,000 ppm (equivalent to intake levels substantially exceeding human exposure scenarios), with systemic NOAELs at 1,000 ppm based on parental effects.^[22] Chlorpropham has not been classified as a reproductive toxicant under regulatory frameworks, including those of the European Food Safety Authority (EFSA), due to the absence of specific reproductive endpoint disruptions at relevant doses.^[45] Standard genotoxicity evaluations, including the Ames bacterial reverse mutation test conducted with and without metabolic activation, yielded negative results, indicating no direct mutagenic activity relevant to developmental or reproductive outcomes.^[13] EFSA's precautionary concerns regarding potential risks, which contributed to EU restrictions, stemmed from modeled genotoxicity of metabolites like 3-chloroaniline rather than empirical causation in core developmental or reproductive assays.^[45] Actual human exposures via potato residues rarely approach the high thresholds (e.g., >200 mg/kg/day equivalents) where effects were observed in animals, underscoring minimal practical risk.^[42]

Human Exposure and Residue Risks

Human exposure to chlorpropham primarily occurs through dietary intake from residues on treated potatoes and, to a lesser extent, occupational contact during application or storage handling. Residue monitoring in potatoes shows concentrations typically ranging from 0.01 to 23 ppm shortly after treatment, with an average of approximately 2.5-3 ppm across sampled batches, and levels generally declining during prolonged storage due to volatilization and degradation.^[46] In the US and Canada, post-2020 monitoring data indicate that 90% or more of potato samples contain detectable residues, often averaging near 3 ppm even after washing, but with no exceedances of established tolerances in regulated imports or domestic produce.^[47] Estimated dietary exposure remains well below the acceptable daily intake (ADI) of 0.05 mg/kg body weight per day, with long-term intake assessments showing less than 1% of the ADI for average consumers reliant on potato-heavy diets.^[3]^[40] Acute dietary risks are negligible, as residue levels post-cooking (e.g., boiling or frying) further reduce exposure through partitioning into water or oil, and potatoes constitute a fraction of overall caloric intake.^[41] Occupational exposure risks are mitigated by personal protective equipment (PPE) such as respirators and gloves during fogging applications in storage facilities, with EPA assessments indicating margins of safety exceeding requirements even in high-exposure scenarios without widespread health incidents reported.^[48]^[49] Post-2020 surveillance in North America has not documented verified cases of acute poisoning or long-term health correlations attributable to chlorpropham, consistent with its low dermal absorption and absence of established occupational exposure limits signaling imminent hazard.^[50]

Environmental Impact

Degradation and Persistence

Chlorpropham degrades primarily via microbial metabolism in aerobic soil environments, where soil microorganisms cleave the carbamate ester bond, leading to mineralization into carbon dioxide, water, chloride ions, and other non-toxic fragments. Reported field half-lives range from less than 30 days to 65 days, influenced by factors such as temperature (shorter at higher temperatures, e.g., 30 days at 29°C versus 65 days at 15°C), soil moisture, and organic matter content, which enhance microbial activity.^[2]^[1]^[51] Hydrolysis proceeds slowly under neutral environmental pH conditions (pH 5–9), with the compound demonstrating stability and half-lives exceeding typical field exposure periods, though rates increase in alkaline media. Photodegradation contributes to breakdown upon exposure to ultraviolet light, particularly on plant surfaces or shallow soil, yielding products like 3-chlorophenyl isocyanate and further fragments, but this pathway is secondary to microbial processes in buried agricultural applications.^[52]^[53] In post-harvest potato storage, persistence extends to several months under dry, low-temperature conditions (e.g., 8–12°C), where limited moisture restricts microbial degradation; however, residues do not accumulate in soil or subsequent crops due to bio-dilution during tuber sprouting and plant growth, coupled with volatilization and gradual breakdown upon field replanting. Application methods, such as thermal fogging for vapor deposition versus direct soil incorporation, influence persistence by affecting initial distribution and exposure to degrading factors, with fogged residues showing higher surface-level photodegradation but slower overall dissipation in enclosed stores. Field trials confirm minimal carryover residues (typically <0.1 mg/kg) in progeny tubers from treated seed stock, attributable to degradation rates outpacing plant uptake and dilution effects.^[54]

Effects on Non-Target Organisms

Chlorpropham exhibits moderate acute toxicity to aquatic organisms, with 96-hour LC₅₀ values of 7.8 mg/L for rainbow trout (Oncorhynchus mykiss) and 6.3 mg/L for bluegill sunfish (Lepomis macrochirus).^[3]^[55] For aquatic invertebrates, the 48-hour EC₅₀ for Daphnia magna is 3.7 mg/L, while algal growth inhibition shows a 72-hour ErC₅₀ of 1.65 mg/L for Navicula pelliculosa.^[3] Chronic endpoints include a 21-day NOEC of 0.32 mg/L for early-life-stage fish (Brachydanio rerio) and 1 mg/L for Daphnia magna reproduction.^[3] Regulatory assessments indicate low risk to aquatic species under typical use with mitigation measures, such as buffer zones, due to limited environmental exposure from post-application runoff, though higher risks may occur in specific scenarios like venting from storage.^[38] Avian toxicity is low, with acute oral LD₅₀ values exceeding 2000 mg/kg body weight for bobwhite quail (Colinus virginianus) and similar species, classifying it as practically non-toxic to birds.^[3]^[2] Short-term dietary LC₅₀ exceeds 5170 mg/kg feed, and chronic 21-day NOEL is 94.7 mg/kg body weight per day, supporting low acute and long-term risks to birds after exposure refinements in risk assessments.^[3]^[38] Field-relevant studies show no significant adverse effects on bird populations attributable to chlorpropham. For bees, acute contact LD₅₀ is 96.1 μg per bee and oral LD₅₀ is 505 μg per bee for honeybees (Apis spp.), indicating moderate toxicity, though no acute harm occurs at field application rates when used as directed.^[3]^[2] Chronic 10-day LDD₅₀ is 12.0 μg per bee per day, and regulatory reviews identify potential high risks to adult bees and larvae from chronic exposure via contaminated weeds or residues, with data gaps for sublethal effects on hypopharyngeal glands and non-Apis species like bumblebees.^[3]^[38] Empirical field data do not demonstrate population-level declines in pollinators linked to chlorpropham use. Overall, long-term ecosystem studies lack robust evidence of chlorpropham-driven declines in non-target wildlife populations, with risks primarily assessed via laboratory endpoints rather than widespread field observations.^[38]

Regulatory Status

Historical Approvals and Reregistrations

Chlorpropham was first registered by the United States Environmental Protection Agency (EPA) in 1962 for use as a pre-emergence and post-emergence herbicide, as well as a plant growth regulator, primarily to control weeds and suppress sprouting in stored potatoes based on toxicity and efficacy data submitted by registrants.^[22]^[42] By the 1990s, following the Food Quality Protection Act of 1996, the EPA conducted a comprehensive reregistration review, culminating in the Reregistration Eligibility Decision (RED) issued in October 1996, which affirmed eligibility for continued registration of potato post-harvest sprout suppression uses after evaluating human health, environmental fate, and ecological effects data.^[52]^[1] This decision concluded that chlorpropham posed acceptable risks when used according to label directions, with tolerances established for residues in potatoes and processed commodities supported by residue studies demonstrating levels below thresholds of concern.^[48] In the European Union, chlorpropham received authorization for plant protection product uses, including potato sprout inhibition, under the framework of Council Directive 91/414/EEC and subsequent regulations, with approvals renewed periodically based on dossiers assessing toxicological profiles, residue dynamics, and environmental behavior.^[1] Pre-2019 evaluations by the European Food Safety Authority (EFSA) and member states set maximum residue levels (MRLs) empirically, such as 10 mg/kg for potatoes, informed by field trials and metabolism studies showing rapid decline under storage conditions.^[40] These reviews prioritized applications where benefits in preventing post-harvest losses outweighed potential risks, conditional on good agricultural practices like ventilation and dosage limits.^[56] Internationally, approvals in jurisdictions like Canada and Australia mirrored U.S. and EU precedents, with registrations dating to the mid-20th century and periodic reaffirmations through data-driven reassessments emphasizing efficacy in sprout control against identified hazards.^[13] Such historical endorsements relied on empirical evidence from registrant-submitted studies, including acute and chronic toxicity tests in mammals, which supported safe use profiles under regulated conditions.^[48]

Bans and Restrictions by Jurisdiction

In the European Union, approval for chlorpropham as a plant growth regulator was not renewed under Commission Implementing Regulation (EU) 2019/989, with the decision announced on June 17, 2019, citing insufficient data to address genotoxicity concerns raised in the 2017 EFSA peer review and gaps in residue risk assessments for metabolites like 3-chloroaniline.^[57]^[58] Use of existing stocks was permitted until October 9, 2020, after which the substance was fully prohibited for agricultural applications, including potato sprout suppression.^[59] Post-Brexit, the United Kingdom aligned with the EU decision, maintaining the non-renewal of chlorpropham authorization; final applications were required to cease by October 8, 2020, in Great Britain, with ongoing monitoring for residues from historic use in potato stores.^[60] In the United States, chlorpropham remains federally approved by the EPA under its Reregistration Eligibility Decision (RED) finalized in September 1995, with tolerances established for residues on potatoes and other crops, and no revocation or full ban enacted as of 2025 despite updated chronic reference dose values in regional screening levels.^[1]^[61] State-level scrutiny exists, such as consumer advocacy reports highlighting residue levels in produce, but federal registration persists without the genotoxicity-driven restrictions seen in the EU.^[5] Canada continues to register chlorpropham-containing products for potato sprout inhibition, with at least 26 formulations authorized as of recent Health Canada listings and no re-evaluation indicating prohibition, though maximum residue limits (MRLs) are enforced and adjusted based on import monitoring.^[47]^[62] Globally, regulatory approaches vary; for instance, several Asian jurisdictions permit chlorpropham use with MRLs tailored to trade requirements, contrasting EU bans, while export-oriented production in non-banning regions supplies markets with adjusted residue tolerances derived from testing data.^[63]

Controversies and Alternatives

Debates Over Risk Assessment

The European Food Safety Authority's 2017 peer review identified genotoxicity risks from chlorpropham and its metabolite 3-chloroaniline, citing positive in vitro assays and structural alerts, which contributed to the EU's non-renewal of approval in 2019 despite negative in vivo micronucleus tests for the parent compound.^[58] Critics, including regulators outside the EU, argued this emphasized precautionary interpretations of in vitro data over comprehensive in vivo evidence, potentially leading to overregulation of low-residue exposures where no causal harm has been demonstrated in long-term use.^[38] The US Environmental Protection Agency, in its 1999 reregistration eligibility decision updated through 2010 assessments, classified chlorpropham as non-carcinogenic (Group E) and deemed metabolite potency low relative to exposure margins, highlighting a evidence-based threshold approach absent overt epidemiological signals.^[52] Proponents of the EU stance invoked developmental toxicity findings, such as mouse studies showing malformations and circulatory disruptions at doses exceeding 100 mg/kg body weight, asserting these justify restrictions even without direct human parallels, under a precautionary framework prioritizing potential vulnerabilities.^[64] Counterarguments emphasized dose irrelevance, noting that real-world human exposures from potato residues—estimated by EFSA at levels yielding short- and long-term intakes below acute reference doses for cross-contamination scenarios—fall orders of magnitude below tested thresholds, with no supporting human epidemiology linking chlorpropham to reproductive or oncogenic outcomes after decades of application.^[65] The Joint FAO/WHO Meeting on Pesticide Residues similarly concluded in 2005 that in vitro genotoxicity signals did not translate to plausible human risks, underscoring debates over extrapolating high-dose animal data to trace residues.^[41] Dissenting expert views, reflected in initial European Commission consultations like the 2019 ScoPAFF meeting where support for the ban fell short of consensus, questioned the weighting of metabolite risks—primarily from 3-chloroaniline's in vitro activity—against integrated toxicokinetic data showing rapid degradation and minimal systemic accumulation.^[66] These perspectives advocate for apical endpoints like chronic rodent bioassays, which showed no clear carcinogenicity for chlorpropham, over mechanistic alerts, arguing that regulatory asymmetry (e.g., US tolerance persistence versus EU prohibition) illustrates tensions between hazard identification and probabilistic risk characterization.^[67]

Post-Ban Challenges and Substitutes

The European Union's prohibition of chlorpropham (CIPC) as a potato sprout suppressant, effective January 1, 2020, precipitated storage challenges characterized by elevated sprouting rates and diminished shelf life for ware potatoes. Industry stakeholders reported difficulties in maintaining stock quality without CIPC, which had previously enabled storage for up to 10 months under controlled conditions; alternatives often necessitated more frequent interventions or environmental adjustments, resulting in operational inefficiencies and potential post-harvest losses exceeding those under prior regimes.^[35]^[68] Potato processors and growers increasingly turned to approved substitutes such as ethylene, spearmint oil, and maleic hydrazide, though these exhibited inferior efficacy relative to CIPC in suppressing sprouts at typical storage temperatures of 8–12°C. Ethylene, a gaseous plant hormone applied continuously via generators, delays sprouting but requires sealed facilities and consistent ventilation, with application costs around £3.50 per tonne—nearly triple CIPC's £1.20 per tonne.^[69]^[14] Spearmint oil (carvone-based), deployed as a volatile fog, demands multiple treatments and incurs £4.50 per tonne, while maleic hydrazide, a pre-harvest foliar treatment at £2.00 per tonne, provides residual control but performs best in combination with volatiles and can influence processing attributes like fry color.^[69]^[70]^[30] These adaptations have imposed higher operational expenses on the sector, with volatile-based systems elevating energy and labor demands; for instance, spearmint oil and ethylene often yield shorter suppression periods, prompting earlier market releases and contributing to price volatility in EU potato markets. Economic evaluations underscore tensions between such cost escalations—potentially reducing net returns for growers—and the pursuit of residue minimization, as reduced storability risks amplifying food supply disruptions during off-season periods.^[71]^[68] Emerging options like 1,4-dimethylnaphthalene or 3-decen-2-one show promise for processing varieties but remain constrained by regulatory approvals and scalability, leaving gaps in comprehensive replacement strategies.^[30]

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[PDF] Gro-Stop Fog Active Substance: Chlorpropham 300 g/L COUNTRY
Nov 6, 2017 · This document describes the acceptable use conditions required for the re-registration of Gro-Stop Fog containing chlorpropham in Germany. This ...<|control11|><|separator|>
[18]
CN102167670B - Method for producing chlorpropham
The synthetic method of at present Y 3 employing mainly is the isopropyl chlorocarbonate method: namely carry out condensation reaction with m-chloro aniline ...
[19]
Efficient Chlorpropham Synthesis: The Crucial Role of 1-Chloro-3 ...
Oct 17, 2025 · Its production relies on a precisely controlled chemical reaction where 1-Chloro-3-isocyanatobenzene serves as a key precursor. The isocyanate ...
[20]
ICSC 1500 - CHLORPROPHAM - Inchem.org
Molecular mass · 213.7 ; Melting point · 41°C ; Density · 1.18 g/cm³ ; Solubility in water, g/100ml · 0.009 (very poor) ; EXPOSURE & HEALTH EFFECTS. Routes of exposure.
[21]
[PDF] chlorpropham Chemical name: IUPAC: isopropyl 3 ...
No octanol/water partition coefficient was reported for HSA but the chemical nature of the molecule suggests that its fat-solubility would be low. USE PATTERN.
[22]
Pesticide Fact Sheet: Chlorpropham - epa nepis
Types and Methods of Application: Chiorpropham is a selective preplant incorporated, preemerge ce, and postemergence herbicide and plant growth regulator.Missing: properties | Show results with:properties
[23]
Mechanisms of the thermal decay of chlorpropham - ScienceDirect
Since their development in the 1950s, carbamates have found widespread use as agricultural and horticultural pesticides, with 11% of all pesticide usage coming ...Missing: discovery | Show results with:discovery
[24]
Level and fate of chlorpropham in potatoes during storage and ...
Aug 6, 2025 · Chlorpropham concentration on washed and unwashed tubers decreased from approximately 15 mg kg(- 1) after storage for 28 d to approximately 9 mg ...
[25]
Determination of chlorpropham (CIPC) residues, in the concrete ...
The half-lives of CIPC in soil at temperatures of 15 °C and 29 °C were 163 and 27 days, respectively, whereas in lake water, the half-life was 2208 days (Smith ...
[26]
(PDF) The Effects of Chlorpropham Exposure on Field-Grown Potatoes
Aug 7, 2025 · Some plants failed to emerge from seed treated with 5 or 10 ppm CIPC. CIPC treatment resulted in total yield decreases of 26 % (2.5 ppm CIPC) to ...<|separator|>
[27]
The Comparative Cell Cycle and Metabolic Effects of Chemical ...
At high concentration of chlorpropham, respiration and ATP levels were severely depressed, and one would expect an immediate inhibition of mitotic entry.
[28]
Cell Cycle Population Kinetics of Pea Root Tip Meristems ... - jstor
coupling of ATP synthesis, and inhibition of RNA and protein synthesis. Moreland et al. (16) also examined chlorpropham and true to the prediction of Ashton ...
[29]
(PDF) Effect of CIPC on Sprout Inhibition and Processing Quality of ...
Aug 9, 2025 · Spray application of CIPC @ 40 and 60 ml/tonne of potatoes significantly reduced sprouting, suppressed sprout growth and reduced total storage ...
[30]
and post-harvest anti-sprouting treatments to replace CIPC for ...
To avoid losses from sprouting during potato storage, the anti-sprouting agent chlorpropham [CIPC] has been widely used over the past few decades.Missing: peak | Show results with:peak
[31]
https://www.indexbox.io/blog/potato-world-market-overview-2024-5/
[32]
Researchers receive $2M to look for new ways to prevent organic ...
Nov 15, 2023 · Oregon State University researchers have been awarded $2 million from the US Department of Agriculture to develop improved ways of preventing stored potatoes ...
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Maleic and l-tartaric acids as new anti-sprouting agents for potatoes ...
Oct 8, 2021 · We have established that simple maleic acid and l-tartaric acid are effective sprout suppressing agents. Both can hinder sprouting up to 6 weeks and 4 weeks ...
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[PDF] Use of CIPC as a potato sprout suppressant
CIPC is used as a potato sprout suppressant, but concerns exist about residues, breakdown products, and potential harmful effects.
[35]
CIPC in the crossfire: Challenges and possible alternatives
Oct 3, 2021 · CIPC has been proven over time to be an effective and inexpensive sprout inhibitor, in use since 1959 by the potato industry. Growers usually ...
[36]
Chlorpropham Market Size, Trends, Growth Forecast - 2034 - Fact.MR
One of the major applications of chlorpropham is in potato storage, where the chemical acts as a sprout inhibitor. This prolongs the life of potatoes and ...
[37]
[PDF] Material Safety Data Sheet - Greenbook.net
LC50 Inhalation: >476 mg/m3. Chemical Name. LD50 Oral. LD50 Dermal. LC50 Inhalation. Chlorpropham. 4,200 mg/kg Oral LD50 Rat. Chronic Toxicity. Carcinogenicity.
[38]
Peer review of the pesticide risk assessment of the active substance ...
Data were submitted to conclude that the uses of chlorpropham according to the representative uses proposed at EU level result in a sufficient plant growth ...Missing: warehouses | Show results with:warehouses
[39]
[PDF] CHLORPROPHAM (addendum) - Inchem.org
In 2000, the JMPR determined that chlorpropham has low acute toxicity: the oral LD50 in rats was > 2000–4200 mg/kg bw, and the dermal LD50 in both rats and ...
[40]
Reasoned opinion on the setting of temporary maximum residue ...
Jun 10, 2020 · The metabolite 3-chloroaniline included in the residue definition for risk assessment is of higher toxicity than chlorpropham; therefore the two ...
[41]
4.5 Chlorpropham (201) - Pesticide residues in food – 2005
The lowest NOAEL identified from short-term feeding studies was 40 ppm (equal to 2.65 mg/kg bw per day) for effects on the liver in a 90-day study of toxicity ...Missing: chronic | Show results with:chronic
[42]
[PDF] Chlorpropham Registration Review Human-Health Assessment ...
Nov 2, 2010 · The toxicity database for chlorpropham is adequate with the exception of acute and subchronic neurotoxicity studies and an immunotoxicity study ...
[43]
Chlorpropham - an overview | ScienceDirect Topics
Chlorpropham at high oral doses given during the organogenesis period caused malformations and various types of developmental toxicity.Missing: EPA | Show results with:EPA
[44]
CHLORPROPHAM - Inchem.org
The developmental toxicity of chlorpropham was studied in rats and rabbits. In rats, the NOAEL for maternal toxicity was 200 mg/kg bw per day on the basis ...
[45]
Peer review of the pesticide risk assessment of the active substance ...
Jul 26, 2017 · In the acute toxicity studies, chlorpropham was of low toxicity (orally, dermally or by inhalation), not a skin or eye irritant nor a skin ...
[46]
Unearthing The Facts: Chlorpropham Residues In Potatoes And ...
However, recent data reveals a startling finding: the average concentration of chlorpropham in tested potato samples is nearly 3 parts per million (ppm).
[47]
chlorpropham
Ninety percent of the samples contained residues of chlorpropham. The average concentration across all samples was nearly three parts per million – high ...
[48]
Fact Sheet Reregistration Eligibility Decision (RED) Chlorpropham
Toxicity In studies using laboratory animals, Chlorpropham generally has been shown to be of low acute toxicity. It is slightly toxic by the oral route and ...
[49]
[PDF] united states environmental protection agency - Regulations.gov
Sep 27, 2017 · of chlorpropham. This memorandum serves as HED' s occupational and residential exposure risk assessment for chlorpropham. 1. Page 2. 2. It is ...
[50]
[PDF] SAFETY DATA SHEET - Fisher Scientific
Jan 8, 2020 · Skin and body protection. Wear appropriate protective gloves and clothing to prevent skin exposure. Page 3 / 7. Page 4. Chlorpropham.
[51]
[PDF] Park, Laura Jane (2004) Chlorpropham distribution in potato stores ...
• Chlorpropham (CIPC): A carbamate first introduced in the 1950s by Marth and. Schultz of Pittsburgh Plate and Glass Co of the USA. Currently the only ...Missing: discovery | Show results with:discovery
[52]
Fact Sheet: Reregistration Eligibility Decision (RED): Chlorpropham
Regulatory History Chlorpropham was registered in the United States in 1962 as a pre-emergence and post-emergence herbicide and as a plant growth regulator. It ...
[53]
[PDF] chlorophenyl) carbamate (chlorpropham) herbicide in the environ
May 1, 2011 · degradation, metabolism and persistence in soil and water (Cooping et al., ... half life periods of chlorpropham in water and acidlbase ...
[54]
Understanding the persistence, transformation and fate of CIPC ...
Understanding the persistence, transformation and fate of CIPC (Chlorpropham) in commercial potato stores to help guard against cross-contamination.
[55]
https://www.sigmaaldrich.com/US/en/sds/SIAL/45393
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The Worry with CIPC - Seed World
Apr 12, 2021 · A 'ban' on the use of CIPC for potato growers in the EU has the potato industry on both sides of the pond concerned. When chlorpropham ...
[57]
[PDF] COMMISSION IMPLEMENTING REGULATION (EU) 2019 - EUR-Lex
Jun 18, 2019 · (16) Commission Implementing Regulation (EU) 2018/917 (7) extended the expiry date of chlorpropham to 31 July 2019 in order to allow the ...
[58]
Peer review of the pesticide risk assessment of the active ... - EFSA
Jul 26, 2017 · The conclusions were reached on the basis of the evaluation of the representative uses of chlorpropham as a plant growth regulator on potatoes ...Missing: reproductive | Show results with:reproductive
[59]
European ban on CIPC poses a problem for potato storage
Dec 18, 2019 · The European Union (EU) has decided to prohibit the use of this substance. This means that it may no longer be used as, among other things, a potato sprout ...
[60]
Managing residues from historic CIPC use in potato stores | AHDB
Following non-renewal in the EU, final use of products containing chlorpropham (CIPC) had to be completed in GB by 8 October, 2020.Missing: commercial | Show results with:commercial
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Regional Screening Levels (RSLs) - What's New | US EPA
Chemicals with new toxicity values due to OPP updates are: Acephate has a new chronic RfD,; Chlorpropham has a new chronic RfD,; Cyhalothrin chronic RfD was ...
[62]
Pesticide Product Information - Health Canada
PLANT GROWTH REGULATOR. Registration Status, Registered. Status Expiry Date, 31-DEC-28. Re-evaluation Status, NO. Product Name, PASSION KRAFTS OIL OF BLACK ...
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Double standards, double risk: Banned pesticides in Europe's food ...
Sep 24, 2024 · This report seeks to shed light on the EU's unethical double standards regarding banned and hazardous pesticides and calls on policymakers to take decisive ...
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Developmental toxicity of chlorpropham in mice - ScienceDirect
The present studies were designed to evaluate the developmental toxicity of chlorpropham in mice. The first study was conducted to determine administration ...
[65]
Reasoned opinion on the setting of temporary maximum residue ...
Jun 10, 2020 · ... Regulation (EC) No 396/2005 on the safety of a proposed temporary maximum residue level (tMRL) for chlorpropham in potatoes to consumers.
[66]
Not enough support for European ban on potato sprout inhibitor ...
The European Commission wants to ban the sprout inhibitor that is formally regulated as a pesticide. However, in the ScoPAFF were not enough votes to approve ...Missing: jurisdictions | Show results with:jurisdictions
[67]
Fast and economic method for chlorpropham residues screening in ...
Chlorpropham is a selective and systemic herbicide extensively used to control sprouting, a major process affecting the quality of stored potatoes.
[68]
Potato storage without Chlorpropham requires sprout inhibitor that ...
Jun 28, 2021 · In Europe, the European Commission has decided that potato growers are no longer allowed to use Chlorpropham in the storage of potatoes.
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How ethylene can help control sprouting in potato stores
Apr 23, 2020 · Cost (£/t). Packing (refrigerated 3.5C). CIPC (one dose), 1.20. Maleic hydrazide, 2.00. Spearmint oil (one dose), 4.50. Ethylene, 3.50.
[70]
Sprout Suppression - AHDB Horticulture
Prior to non-renewal, chlorpropham (CIPC) was the most important sprout suppressant. At its peak, CIPC made up in excess of 90% of pesticide treatments to ...Missing: ROI | Show results with:ROI
[71]
The chlorpropham file: soon to be forbidden, but now still in your ...
The use of chlorpropham (CIPC) will be forbidden by the European Commission in all EU member states – including the Netherlands – in the near future.