4'-Aminopropiophenon

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity 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 and plant life; and conformance with environmental and public health regulations.

0.51 [mg/m3]

5.6 [mg/m3]

35 [mg/m3]

For emergency situations, wear a positive pressure, pressure-demand, full facepiece self-contained breathing apparatus (SCBA) or pressure- demand supplied air respirator with escape SCBA and a fully-encapsulating, chemical resistant suit. (EPA, 1998)

The bioactivation of the cyanide antidote methemoglobin former 4-aminopropiophenone (4-PAPP) was studied using rat and human microsomes. With rat liver and NADPH in single and two-compartment systems, dapsone and benzocaine were more potent methemoglobin generators compared with 4-PAPP. In the single compartment studies, the order of potency of inhibition of 4-PAPP-mediated methemoglobin formation was cimetidine (1.5 mM)>isoniazid (500 uM)/diethyldithiocarbamate (DDC, 1 mM)>erythromycin (500 uM). Human liver microsomal activation of 4-PAPP in the two-compartment system was partially inhibited by both DDC and cimetidine. These preliminary studies suggest that 4-PAPP may be metabolized by /cytochromes P450/ 2C11, 2E1 and 3A in the rat and /cytochromes P450/ 2C, 2E1 and probably 3A4 in man.

Nitrobenzene, aniline, p-aminotoluene (p-AT), p-aminoacetophenone (p-AAP) and p-aminopropiophenone (p-APP) have widely different activities as methemoglobin-forming agents in mice. As assessed by circulating levels after intra-peritoneal administration, p-AT was the least potent compound of the series, but nitrobenzene and aniline were also only weakly active even at lethal doses. Three hydroxylamine analogues from the above series were all about equipotent as methemoglobin forming agents in mice. Moreover, at a dose of 0.1 mole/kg each produced a transient methemoglobinemia that was remarkably similar to that resulting from p-APP. A methemoglobinemia with similar temporal characteristics was also produced by o-aminophenol, but this compound is about ten times less potent. p-Aminophenol was even weaker, being about as active as aniline. When aniline or nitrobenzene was given in combination with sodium nitrite, circulating methemoglobin levels were prolonged. Such a synergism was not seen when either was given in combination with p-APP. Methylene blue in vivo attenuated the methemoglobinemic response to both p-APP and nitrite. It was more effective, however, against the latter, as evaluated at doses that produced equivalent peak circulating levels. In its time pattern the effect of nitrite was similar in vivo (intact mouse) and in vitro (mouse red cell suspension). In contrast, methemoglobinemia produced by phenylhydroxylamine appears to persist longer in red cells than in the intact animal. Apparently, factors external to the red cell are important in terminating some kinds of induced methemoglobinemias.

Pretreatment with sodium nitrite or p-aminopropiophenone has been shown to protect armadillos, rabbits, and mice from death by parenteral sodium sulfide. The degree of protection correlated with anticipated levels of methemoglobinemia. Pretreatment of mice with nitrite or PAPP significantly prolonged their survival during continuous vapor exposure to any one of three concentrations of hydrogen sulfide, but the greatest protection occurred at the intermediate concentration. Under certain conditions propylene glycol also prolonged survival time, probably by a nonspecific action in depressing respirations. The mechanism of protection against sulfide by methemoglobinemia is discussed with reference to the formation of sulfmethemoglobin and its possible fate in vivo.

LD50; Species: Coturnix japonica (Japanese Quail) captive breeding colony, oral via capsule >316 mg/kg

LD50; Species: Sturnus vulgaris (European Starling) wild, oral via capsule >316 mg/kg

LD50; Species: Agelaius phoeniceus (Red-Winged Blackbird) wild, oral via capsule 133 mg/kg

LD50; Species: Pica pica (Black-Billed Magpie) wild, oral via capsule 178 mg/kg

For more Ecotoxicity Values (Complete) data for 4-Aminopropiophenone (6 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 50(SRC), determined from a structure estimation method(2), indicates that 4-aminopropiophenone is expected to have very high mobility in soil(SRC). However, aromatic amines are expected to bind strongly to humus or organic matter in soils due to the high reactivity of the aromatic amino group(3,4), suggesting that mobility may be much lower in some soils(SRC). Volatilization of 4-aminopropiophenone from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 4.6X10-9 atm-cu m/mole(SRC), using a fragment constant estimation method(5). 4-Aminopropiophenone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.0X10-4 mm Hg at 25 °C(SRC), determined from a fragment constant method(6). Biodegradation data were not available(SRC, 2011).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 50(SRC), determined from a structure estimation method(2), indicates that 4-aminopropiophenone is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 4.6X10-9 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of one(SRC), from an estimated log Kow of 1.25(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2011).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 4-aminopropiophenone, which has an estimated vapor pressure of 5.0X10-4 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase 4-aminopropiophenone 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 1.3 hours(SRC), calculated from its rate constant of 9.9X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase 4-aminopropiophenone will be removed from the atmosphere by wet or dry deposition. 4-Aminopropiophenone absorbs light at wavelengths of 310.3 nm(4), and therefore may be susceptible to direct photolysis by sunlight(SRC).

/BIRDS and MAMMALS/ Development of p-aminopropiophenone (PAPP) as a toxicant for pest predator management in New Zealand and Australia prompted investigation of its toxicity to potential nontarget species. Acute oral toxicity of PAPP in brushtail possums (Trichosurus vulpecula), dama wallabies (Macropus eugenii), and Mallards (Anas platyrhynchos) was estimated in pen trials, carried out between February 2000 and September 2001. The susceptibility of possums (LD50>or=500 mg/kg) and wallabies (LD50 89 mg/kg) to PAPP was low in comparison to noncarnivorous placental mammal species, but ducks (LD50 38 mg/kg) were more susceptible than other bird species. These results suggest that the nontarget hazard to possums and wallabies from PAPP bait applied for pest predator control would be low. However, future development of PAPP as a vertebrate pest control agent should include rigorous assessments of the hazard posed by bait formulations to bird species and provision for delivery techniques that could mitigate exposure of nontarget birds.

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 4-aminopropiophenone can be estimated to be 50(SRC). According to a classification scheme(2), this estimated Koc value suggests that 4-aminopropiophenone is expected to have very high mobility in soil. However, aromatic amines are expected to bind strongly to humus or organic matter in soils due to the high reactivity of the aromatic amino group(3,4), suggesting that mobility may be much lower in some soils(SRC).

/HUMAN EXPOSURE STUDIES/ This study used human volunteers from a factory site to investigate the methemoglobin (MetHb) response in humans. There were 51 individuals (assumed to be male, but this is not stated), aged between 23- 52 years of age. There exposures were to 100 mg (13 cases), 80 mg (37 cases) or 50 mg (1 case) PAPP. The study showed that it takes 15- 30 minutes for MetHb to develop, with the peak level being reached 1- 2 hours after consumption. In most individual receiving 80 or 100 mg the MetHb level was higher than 5% for at least 4 hours. The group data summaries were: 100 mg group: distribution of maximum level was 22 +/-14% (range 2- 48%); 80 mg group: distribution of maximum level was 13.1 +/-9% (range 0- 43%). [The one individual consuming 50 mg had 7% MetHb.] Effect of body weight: Due to the lack of adjustment of dose based on body weight, the MetHb response varied depending on body weight. For individual receiving 100 mg with MetHb concentrations >20% the average body weight was 63kg (average dose (1.28 mg/kg bw), while for those with 20%, the average body weight was 78 (1.59 mg/kg bw). For the individuals receiving 80 mg, the equivalent data are for MetHb concentrations >10% the average body weight was 71kg (average dose (1.13 mg/kg bw), while for those with 10%, the average body weight was 76 (1.05 mg/kg bw). Effect of food consumption: The study also appeared to demonstrate (based on different data) involving individuals who had consumed PAPP a long or short time after a meal that the MetHb level tends to be higher if it is a long time since a meal had been consumed, which was believed to be due to stomach acidity, but it may also related to dissolution of PAPP in lipid. Variability: The study also demonstrated that a small number of individuals are relatively resistant to the effects of MetHb generating substances. The report indicates 2-3 individuals in their group of 51 [but the generalizability of this to the human population needs caution, as the study is presumed to be of adult, male Caucasians only]. Questionnaires did not identify any subjective discomfort associated with the exposure to PAPP, even in individuals who had MetHb levels of 30- 40% and who were demonstrating clear signs of methemoglobinemia (blue lips). No changes in the ventilation rates or blood pressure were seen in comparison to pre-treatment values. Electrocardiograms for 20 of the individuals were carried out. There were no changes in 18 individuals, but two individuals, both of whom received the 80 mg dose [aged 25 and 37, weighing 67kg and 100 kg respectively] were found to have slight changes that were reported as minimal. The MetHb levels were respectively in these individuals were 24% and 4.5%.

4-Aminopropiophenone's production and use as an antidote(1) may result in its release to the environment through various waste streams(SRC). Its use as a vertebrate toxic agent in New Zealand(2) will result in its direct release to the environment(SRC).

An estimated BCF of one was calculated in fish for 4-aminopropiophenone(SRC), using an estimated log Kow of 1.25(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Henry's Law constant for 4-aminopropiophenone is estimated as 4.6X10-9 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that 4-aminopropiophenone is expected to be essentially nonvolatile from water and moist soil surfaces(2). 4-Aminopropiophenone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.0X10-4 mm Hg(SRC), determined from a fragment constant method(3).

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ /In a/ 14 day study (with 14 day recovery period), Rats were administered p-aminopropiophenone at/ dose levels /of/ 0, 35/20, 90/50, 140/130 mg/kg bw/day in males/females respectively. /There was no/ NOAEL established. /A/ LOAEL /of/ 35 mg/kg bw/day in males and 20 mg/kg bw/day in females, due to enlarged spleens, associated with erythroid hyperplasia, sinusoidal enlargement and pigment /was established/. [Reduced red blood cell count associated with increased packed cell volume and red cell hemoglobin were clearly evident in the mid dose groups. Raised methemoglobin was seen at all dose levels. At the top dose (140 mg/kg bw/day in males and 130 mg/kg bw/day pigment was also present in Kupffer cells of the liver and renal proximal tubular epithelial cells.]

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ /In a/ 14 day study (with 14 day recovery period), monkeys were administered p-aminopropiophenone at/ dose levels /of/ 0, 17, 50 and 150 mg/kg bw/day. Methemoglobin was clearly raised at both 17 and 50 mg/kg bw/day, but the degree of elevation is of questionable clinical significance as the highest group mean at any time point was 5.1% on Day 14 (males) and 8.2 on Day 11 in females) at 50 mg/kg bw/day. None of these animals had concentrations above 10% at any time point. In the top dose groups the highest value was 31.6% in one male on Day 6 (the only value for males above 30%), while in females one animal had 3 readings in excess of 30% and was consistently higher than its peers. While the increase /in Heinz Body formations/ at 17 mg/kg bw/day is relatively small, an increase in Heinz Body formation occurred at this dose in ... 2 males and 3 females. /A/ NOAEL /was not/ established. /A/ LOAEL of 17 mg/kg bw/day based on raised methemoglobin concentrations, clinical hematology primarily increased Heinz Bodies and clinical chemistry. ... The hematology data suggest an effect of PAPP on erythropoiesis aside from oxidative damage and hemolysis.

/GENOTOXICITY/ In an Ames mutagenicity assay using Salmonella typhimurium stains TA1535, TA1537, TA1538, TA98, TA100 and TA1537R+, PAPP (no information on source, purity or concentrations) with and without metabolic activation (S9) /was negative for mutagenic effects/.

The comment is made that the frequency of polymorphism for MetHb reductase in caucasians is rare, and 15% in Inuit [Eskimos].

The frequency of glucose-6-phosphate dehydrogenase [deficiency] allele is up to 0.25% in general, but in subpopulations of tropical Africa, the Middle East and subtropical Asia, some areas of the Mediterranean and Papua New Guinea, frequencies as high as 5- 25% are found. ... Glucose-6-phosphate dehydrogenase deficiency is an X-chromosome linked recessive hereditary disease (which means significant phenotypic expression is more common in males, but heterozygous women can also develop haemolytic attacks). This is the most common human genetic defect, and occurs widely in people from Africa, Middle East and South Asia and people having genetic lineage to people from those areas. It is associated with some resistance to malaria. ...

... Genetic variants in cytochrome B5 (seen in people of Mediterranean or African origin) and hemoglobin (such as sickle cell disease) are more susceptible /to the effects of p-aminopropiophenone/.

Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. 4-Aminopropiophenone is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 100 or 10,000 lbs. Extremely hazardous substances that are solids are subject to either of two threshold planning quantities ... The lower quantity applies only if the solid exists in powdered form and has a particle size less than 100 microns; or is handled in solution or in molten form; or meets the criteria for a National Fire Protection Association (NFPA) rating of 2, 3 or 4 for reactivity. If the solid does not meet any of these criteria, it is subject to the upper ... threshold planning quantity ... .

/p-Aminopropiophenone is used as a/ more effective and specific control of target pests (stoats, ferrets and feral cats) which will assist in reversing the decline in indigenous biota (specifically, protected bird species such as the kiwi). ... PAPP Paste A, PAPP Paste B and PAPP Ready-to-use Bait are intended to be used as vertebrate toxic agents.

MEDICATION