Diphenylamine

Pesticide -> EPA IRIS

Plant Growth Regulators

Active substance -> EU Pesticides database: Not approved

Pesticide (Diphenylamine (DPA)) -> USDA PDB

log Kow = 3.50

3.50

3.5

3.57

1.068 at 141.8 °F (USCG, 1999) - Denser than water; will sink

1.16

1.2 g/cm³

1.16

1.158 @ 22°C

1.16

Monoclinic leaflets from dilute alcohol

Crystals

Colorless, tan, amber, or brown crystalline solid.

less than 1 mg/mL at 61 °F (NTP, 1992)

1 g dissolves in 2.2 ml of alcohol, 4 ml propyl alcohol; Freely sol in benzene, ether, glacial acetic acid, carbon disulfide.

Very sol in ethanol, acetone, benzene, carbon tetrachloride, pyridine, ethyl acetate; sol in ether, acetic acid; slightly sol in chloroform

Soluble in oxygenated and aromatic solvents

In water, 53 mg/liter @ 20 °C

0.053 mg/mL at 20 °C

307 °F (NTP, 1992)

307 °F

153 °C OC

153 °C c.c.

307 °F

307 °F

Danger

H301: Toxic if swallowed [Danger Acute toxicity, oral]

P260, P261, P262, P264, P270, P271, P273, P280, P301+P316, P302+P352, P304+P340, P316, P319, P321, P330, P361+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)

Danger

H301+H311+H331 (10.1%): Toxic if swallowed, in contact with skin or if inhaled [Danger Acute toxicity, oral; acute toxicity, dermal; acute toxicity, inhalation]

P203, P260, P261, P262, P264, P264+P265, P270, P271, P273, P280, P301+P316, P302+P352, P304+P340, P305+P351+P338, P316, P318, P319, P321, P330, P337+P317, P361+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)

Chemical: Benzenamine, N-phenyl-

Hazard Traits - Carcinogenicity

Commission Regulation (EC) No 33/2008

Benzenamine, N-phenyl- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Benzenamine, N-phenyl- are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Diphenylamine is listed in the dataset of EPA Human Health Benchmarks for Pesticides under the Safe Drinking Water Act (40 eCFR 141)

2009/859/EC, Reg. (EU) No 578/2012

Special Hazards of Combustion Products: Toxic oxides of nitrogen may form in fire.

Combustible. Gives off irritating or toxic fumes (or gases) in a fire. Finely dispersed particles form explosive mixtures in air.

The toxicity of diphenylamine is similar to that of aniline. Hepatotoxic effects have been demonstrated in animals. It can cause bladder irritation and induce methemoglobinemia in workers. As a skin sensitizer it cross-reacts with p-phenylene diamine. [ACGIH] May have effects on the kidneys and blood; A skin, eye, and respiratory tract irritant; [ICSC]

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. Diphenylamine is included on this list.

Section 8(a) of TSCA requires manufacturers of this chemical substance to report preliminary assessment information concerned with production, exposure, and use to EPA as cited in the preamble in 51 FR 41329.

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their future use. Under this pesticide reregistration program, EPA examines health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether they are eligible for reregistration. In addition, all pesticides must meet the new safety standard of the Food Quality Protection Act of 1996. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA '88 were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern and List D pesticides of less concern. Diphenylamine is found on List B. Case No: 2210; Pesticide type: fungicide, herbicide; Case Status: RED Approved 9/1997; OPP has made a decision that some/all uses of the pesticide are eligible for reregistration, as reflected in a Reregistration Eligibility Decision (RED) document .; Active ingredient (AI): diphenylamine; Data Call-in (DCI) Date(s): 01/10/1991, 10/13/1995; AI Status: OPP has completed a Reregistration Eligibility Decision (RED) for the case/AI.

Tolerances for residues of the plant growth regulator diphenylamine are established in or on the following commodities: Apple, wet pomace; apple from preharvest or postharvest use, including use of impregnated wraps; cattle, fat; cattle, liver; cattle, meat byproducts, except liver; cattle, meat; goat, fat; goat, liver; goat, meat byproducts, except liver; goat, meat; horse, fat; horse, liver; horse, meat byproducts, except liver; horse, meat; milk; sheep, fat; sheep, liver; sheep, meat byproducts, except liver; and sheep, meat.

A time-limited tolerance is established for the indirect or inadvertent residues of diphenylamine in or on the following commodity: pear (Expiration/Revocation Date: 12/1/01).

Fire Extinguishing Agents Not to Be Used: Water or foam may cause frothing.

Use water spray, powder, alcohol-resistant foam, carbon dioxide.

Fresh air, rest.

Rinse and then wash skin with water and soap.

Rinse with plenty of water for several minutes (remove contact lenses if easily possible).

Rinse mouth. Give one or two glasses of water to drink.

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

(General first aid procedures)

Biological Exposure Indices (BEI) [ACGIH] - Methemoglobin in blood = 1.5% of hemoglobin during or at end of shift. [ACGIH]

5.0 [mg/m3], inhalable fraction[German Research Foundation (DFG)]

In general, materials which are toxic as stored or which can decompose into toxic components...should be stored in a cool, well-ventilated place, out of direct rays of the sun, away from areas of high fire hazard, and should be periodically inspected... Incompatible materials should be isolated from each other.

Keep protected from light.

/Store/ separated from strong acids, oxidants.

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

Burn in admixture with flammable solvent in furnace equipped with afterburner and scrubber. Recommendable methods: Incineration ... .

Personal protection: particulate filter respirator adapted to the airborne concentration of the substance. Do NOT let this chemical enter the environment. Sweep spilled substance into covered containers. If appropriate, moisten first to prevent dusting. Then store and dispose of according to local regulations.

SRP: The scientific literature for the use of contact lenses in industry is conflicting. The benefit or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

The worker should wash daily at the end of each work shift.

Work clothing that becomes wet or significantly contaminated should be removed and replaced.

Workers whose clothing may have become contaminated should change into uncontaminated clothing before leaving the work premises.

Diphenylamine (5 mg) together with sodium nitrite (15 mg) fed to rats greatly decreased growth of animals. Kidney and liver toxicities and papillomatous hyperplasia of bladder observed in rats fed diphenylamine and sodium nitrite.

The toxicity of halogenated hydrocarbons such as carbon tetrachloride, hexachlorophene, and bithionol sulfoxide, used in veterinary medicine was diminished by the prior or simultaneous administration of diphenylamine (0.1-10% of the admin hydrocarbon).

...Dimethyl sulfoxide lessened the incidence of papillary lesions from diphenylamine.

Hepatic

Eyes, skin, respiratory system, cardiovascular system, blood, bladder, reproductive system

LC50 Brachydanio rerio (Zebrafish) 2.2 mg/L/48 hr /Conditions of bioassay not specified/

LC50 Oryzias latipes (Japanese medaka) 5.1 mg/L/48 hr /Conditions of bioassay not specified/

LC50 Pimephales promelas (Fathead minnow, 31 day old) 3.79 mg/L/96 hr @ 24.9 °C (95% CI: 3.47-4.14 mg/L); flow through, dissolved oxygen 7.3 mg/L, hardness 48.0 mg/L as calcium carbonate, alkalinity 43.1 mg/L as calcium carbonate, pH 7.8 /99+% pure/

EC50 Pimephales promelas (Fathead minnow, 31 day old) affected fish lost schooling behavior, were hypoactive, swam near the tank bottom and were darly colored. 3.63 mg/L/96 hr @ 24.9 °C (95% CI: 3.31-3.99 mg/L); flow through, dissolved oxygen 7.3 mg/L, hardness 48.0 mg/L as calcium carbonate, alkalinity 43.1 mg/L as calcium carbonate, pH 7.8 /99+% pure/

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1,900(SRC), determined from a log Kow of 3.50(2) and a regression-derived equation(3), indicates that N,N-diphenylamine is expected to have low mobility in soil(SRC). Volatilization of N,N-diphenylamine from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.7X10-6 atm-cu m/mole(SRC) derived from its vapor pressure, 6.7X10-4 mm Hg(4), and water solubility, 53 mg/liter(5). N,N-Diphenylamine is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(4). N,N-Diphenylamine is not expected to biodegrade in soil based on aqueous screening tests(6). N,N-Diphenylamine, present at 30 mg/l, reached 0% of its theoretical BOD in 2 weeks using an activated sludge innoculum at 100 mg/l and the Japanese MITI test(6).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1,900(SRC), determined from a log Kow of 3.50(2) and a regression-derived equation(3), indicates that N,N-diphenylamine is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 2.7X10-6 atm-cu m/mole(SRC), derived from its vapor pressure, 6.70X10-4 mm Hg(4), and water solubility, 53 mg/l(5). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 9.4 and 107 days, respectively(SRC). According to a classification scheme(6), BCFs ranging from 51 to 253(7), suggests bioconcentration in aquatic organisms is moderate(SRC). N,N-Diphenylamine was found to be not readily biodegradable in aqueous screening tests(7). N,N-Diphenylamine, present at 30 mg/l, reached 0% of its theoretical BOD in 2 weeks using an activated sludge innoculum at 100 mg/l and the Japanese MITI test(7).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), N,N-diphenylamine, which has a vapor pressure of 6.7X10-4 mm Hg at 25 °C(2) is expected to exist solely as a vapor in the ambient atmosphere(SRC). Vapor-phase N,N-diphenylamine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 1.9 hours(SRC), calculated from its rate constant of 2.0X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3).

N,N-Diphenylamine was found in domestic and imported apples at avg concns of 0.275 ppm (max, 8.1 ppm; detections, 223 out of 769) and 0.232 ppm (max, 5.9 ppm; detections, 402 out of 1,062), respectively(1). N,N-Diphenylamine was detected in fruits and vegetables (15 of 3,962 sample) at concns between <0.01 and <5 ug/g from samples collected in Ontario, Canada between the years 1991 to 1995(2). As part of the Danish Pesticide Monitoring Program conducted between the years 1995-96, N,N-diphenylamine was detected in 5 of 96 apples and 1 of 33 pear samples(3). In selected agricultural commodities available in Canada, the concn of N,N-diphenylamine ranged from <0.05 to 2.0 ppm in 16 of 676 samples analyzed(4).

The substance can be absorbed into the body by inhalation, through the skin and by ingestion.

inhalation, skin absorption, ingestion, skin and/or eye contact

Diphenylamine uncouples mitochondrial oxidative phosphorylation, resulting in a decrease in hepatocellular ATP content and consequently hepatocyte injury (A15350). Short-term and long-term exposure in animal models results in altered haematological parameters, splenic erythropoiesis, splenic congestion and haemosiderosis (L2078).

Based on a FDA Total Diet Study analysis conducted between the years 1986 to 1991, the avg daily intake of N,N-diphenylamine was determined for eight age groups as follows (all ug/kg body wt/day): 6-11 month old (0.0034), 2 year old (0.0410), 14-16 year old female (0.0073), 14-16 year old male (0.0099), 25-30 female (0.0074), 25-30 male (0.0051), 60-65 year old female (0.0079), and 60-65 year old male (0.0065)(1,2).

Cough. Sore throat.

Redness.

Redness.

Sore throat.

irritation eyes, skin, mucous membrane; eczema; tachycardia, hypertension; cough, sneezing; methemoglobinemia; increased blood pressure, heart rate; proteinuria, hematuria (blood in the urine), bladder injury; In Animals: teratogenic effects

N,N-Diphenylamine had been detected as a volatile organic compound released from textile floor coverings(1). N,N-Diphenylamine was detected in 3 samples of municipal landfill leachate from Gryta, Vasteras, Sweden at concns of 2.3, 3.5, and <2 ug/liter (quantification limit = 2 ug/liter)(2).

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. Diphenylamine is included on this list.

Section 8(a) of TSCA requires manufacturers of this chemical substance to report preliminary assessment information concerned with production, exposure, and use to EPA as cited in the preamble in 51 FR 41329.

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their future use. Under this pesticide reregistration program, EPA examines health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether they are eligible for reregistration. In addition, all pesticides must meet the new safety standard of the Food Quality Protection Act of 1996. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA '88 were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern and List D pesticides of less concern. Diphenylamine is found on List B. Case No: 2210; Pesticide type: fungicide, herbicide; Case Status: RED Approved 9/1997; OPP has made a decision that some/all uses of the pesticide are eligible for reregistration, as reflected in a Reregistration Eligibility Decision (RED) document .; Active ingredient (AI): diphenylamine; Data Call-in (DCI) Date(s): 01/10/1991, 10/13/1995; AI Status: OPP has completed a Reregistration Eligibility Decision (RED) for the case/AI.

Tolerances for residues of the plant growth regulator diphenylamine are established in or on the following commodities: Apple, wet pomace; apple from preharvest or postharvest use, including use of impregnated wraps; cattle, fat; cattle, liver; cattle, meat byproducts, except liver; cattle, meat; goat, fat; goat, liver; goat, meat byproducts, except liver; goat, meat; horse, fat; horse, liver; horse, meat byproducts, except liver; horse, meat; milk; sheep, fat; sheep, liver; sheep, meat byproducts, except liver; and sheep, meat.

A time-limited tolerance is established for the indirect or inadvertent residues of diphenylamine in or on the following commodity: pear (Expiration/Revocation Date: 12/1/01).

This action promulgates standards of performance for equipment leaks of Volatile Organic Compounds (VOC) in the Synthetic Organic Chemical Manufacturing Industry (SOCMI). The intended effect of these standards is to require all newly constructed, modified, and reconstructed SOCMI process units to use the best demonstrated system of continuous emission reduction for equipment leaks of VOC, considering costs, non air quality health and environmental impact and energy requirements. Diphenylamine is produced, as an intermediate or a final product, by process units covered under this subpart.

(ME) MAINE 175 ug/l

(FL) FLORIDA 175 ug/l

.../Diphenylamine/ has been converted to 4-hydroxydiphenylamine in rat and man. An antioxidant DPA actually promotes lipid hydroperoxide formation and oxygen consumption while markedly inhibiting generation of thiobarbituric acid reactive substances. /Diphenylamine/ abolishes formation of cyclooxygenase-dependent conversion products of arachidonate.

The urinary metabolites include 4-hydroxy-DPA, 4,4'-dihydroxy-DPA, and their conjugates. There is no evidence of N-hydroxylation.

...Fate of diphenylamine in dairy cow has been studied. None of the parent compound was detected in the milk or in urine, but small amount (1.4%) were identified in feces. The major metabolites were mono- and di-hydroxylated derivatives. Diphenylamine was rapidly metabolized by beef-liver microsomes.

Fifty percent of 5 ppm diphenylamine disappeared during a 30-minute incubation with liver extract. It was /suggested/ that microsomal hydroxylation of diphenylamine occurs, followed by conjugation and elimination.

Diphenylamine has known human metabolites that include Diphenylamine N-glucuronide.

...Stated to be less readily absorbed through the skin and respiratory tract /than aniline/.

After administration of diphenylamine (5 ppm) in feed to holstein cow for 4 days, 1.4% of dose detected in feces but none in urine or milk.

A Holstein cow was fed diphenylamine at 5 ppm in the diet for 4 days. Residues of diphenylamine were not detected in the milk or urine, and only in small amounts (1.4%) of the total dose were detected in the feces.

Diphenylamine is readily absorbed through inhalation and skin contact.

Used as an antioxidant, stabilizer of explosives, fungicide, and analytical chemical reagent; also used in the manufacture of dyes and pesticides; [ACGIH] Used to make dyes, to stabilize nitrocellulose explosives and celluloid, to treat screwworm topically (veterinary), and to test for nitrate or nitrite poisoning; [Merck Index]

For diphenylamine (USEPA/OPP Pesticide Code: 038501) ACTIVE products with label matches. /SRP: Registered for use in the U.S. but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./

Manufacture of dyes; stabilizing nitrocellulose explosives and celluloid; in analytical chemistry for detection of nitrates, chlorates and other oxidizing substances with which, in presence of sulfuric acid, it gives a deep-blue color.

VET: Topically in anti-screwworm mixtures; in test for nitrate or nitrate poisoning.

Rubber antioxidants and accelerators, solid rocket propellants, pesticides, dyes, pharmaceuticals, storage preservation of apples, stabilizer for nitrocellulose.

For more Uses (Complete) data for N,N-DIPHENYLAMINE (10 total), please visit the HSDB record page.

Six commercial brands of DPA were analyzed for these impurities: o-cyclohexylaniline was in all samples; p-biphenylamine in 4; o-biphenylamine in 3 and p-cyclohexylaniline in 1.

A number of primary and secondary amines have been reported as impurities in commercial DPA, including p-biphenylamine.

...The carcinogen 4-aminodiphenyl may be present as an impurity during manufacturing process. This may be concentrated to significant proportions in tars... At distillation stage... hazard of bladder cancer.

2023: 50,000,000 - <100,000,000 lb

(1984) LESS THAN 2.27X10+6 g

Diphenylamine

Benzeneamine, N-phenyl-

IFRA_STD_135.pdf

38

IFRA 51st Amendment - Guidance for the use of IFRA Standards

Prohibition: This material should not be used as a fragrance ingredient

By heating equal formula weights of aniline and aniline hydrochloride in an autoclave. The product is boiled with dilute hydrochloric acid to remove the unaltered aniline, and the residue is distilled.

... Manufactured by heating aniline by itself, or with phenol, and with an acid catalyst at high temperatures.

GRADES: TECHNICAL; REFINED, FLAKE & FUSED

NO SCALD

SCALDIP

BIG DIPPER

DECCOSCALD EC 282 (25% AI), NO SCALD DPA EC 283 (31% AI), NO SCALD DPA POWDER NO. 31 (83% AI)