Ethyl-N-acetyl-N-butyl-β-alaninat

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 36(SRC), determined from a structure estimation method(2), indicates that ethyl butylacetylaminopropionate is expected to have very high mobility in soil(SRC). Volatilization of ethyl butylacetylaminopropionate 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), based upon its vapor pressure, 1.1X10-3 mm Hg(3), and water solubility, 7.0X10+4 mg/L(3). Ethyl butylacetylaminopropionate is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(3). Biodegradation data in soil were not available(SRC, 2016).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 36(SRC), determined from a structure estimation method(2), indicates that ethyl butylacetylaminopropionate 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), derived from its vapor pressure, 1.1X10-3 mm Hg(4), and water solubility, 7.0X10+4 mg/L(4). Ethyl butylacetylaminopropionate is not expected to undergo hydrolysis; estimated hydrolysis half-lives of 3.8 years and 140 days at pH values of 7 and 8, respectively, were calculated(2). According to a classification scheme(5), an estimated BCF of 6(SRC), from its log Kow of 1.7(4) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2016).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), ethyl butylacetylaminopropionate, which has a vapor pressure of 1.1X10-3 mm Hg at 20 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase ethyl butylacetylaminopropionate 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 13 hours(SRC), calculated from its rate constant of 2.9X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Ethyl butylacetylaminopropionate contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

IDENTIFICATION AND USE: EBAAP is a colorless to slightly yellowish liquid. It is an insect repellent for application to human skin and clothing to repel mosquitoes, flies and ticks. It provides high level of protection for at least 8 hr against Ae. albopictus and for at least 5 hr against C. gelidus, C. tritaeniorhynchus, C. quinquefasciatus, Mansonia dives, M. uniformis, M. annulata, M. annulifera, Anopheles minimus, and An. maculatus. This clearly documents the potential for its use as a topical treatment against a wide range of mosquito species belonging to several genera. HUMAN EXPOSURE AND TOXICITY: Closed epicutaneous irritation test using 15% a.i. was performed in 30 human volunteers. No skin reactions were observed. Repetitive exposure test using 15% a.i. was performed in 10 human volunteers 3 wk at twice/wk (induction phase); 12 d break; then 7th application (challenge). No toxic or allergic reactions were observed. ANIMAL STUDIES: 10% solution in ethanol was applied to shaven nuchal area of 10 guinea pigs. No erythema or edema observed at UV-exposed and unexposed sites. Undiluted EBAAP was applied to shaven dorsal skin (6 hr exposure; recovery period 14 d) of rats. Up to 10 mL/kg bw no systemic reactions observed; erythemas at all dose levels. Mongrel dogs were given undiluted EBAAP by gavage at 1, 2, 4 and 8 g/kg bw. All animals survived; doses of 2 g/kg bw or more induced vomiting after 30-60 minutes followed by salivation after 20-30 minutes. EBAAP was administered orally by gavage at a dose of 999 mg/kg/day to female rabbits. Blood pressure was lower for the 2 treated animals than for the 2 control animals (determined after 8 days of treatment). Various serum chemistry parameters were affected by the treatment. Histopathological evaluation of the treated animals revealed hemorrhages and erosions in the gastric mucosa and intestinal tract, vacuolar degeneration of parenchymal cells and hemosiderosis in the liver, deposition of protein in the Bowman's space of the kidney. Atrophy of the bone marrow was also noted for one rabbit. Artificially inseminated female rabbits were treated orally by gavage with 0 100, 300, or 600 mg/kg/day of EBAAP from day 7 through day 19 of gestation. No treatment-related effects on the does were evident. Likewise, no treatment-related effects were noted on development of the fetuses. S. typhimurium strains TA 98, TA 100, TA 102, TA 1535, and TA 1537 and E. coli WP2 uvrA were treated for 48 hours at 37 °C with EBAAP at concentrations ranging from 5 to 5000 ug/plate with and without metabolic activation. There was no treatment-related increase in the incidence of reverse mutation. ECOTOXICITY STUDIES: No evidences for disruption of the chemical communication of fish and Daphnia by EBAAP were found.

/AQUATIC SPECIES/ Commercial insect repellents like DEET (N,N-diethyl-m-toluamide), EBAAP (IR3535, (3-[N-butyl-N-acetyl]-aminopropionic acid, ethyl ester)) or Icaridine (picaridin, Bayrepel, 1-piperidinecarboxylic acid, 2-(2-hydroxyethyl), 1-methylpropyl ester) are used worldwide to protect against biting insects and ticks. The detection of these repellents in surface waters in concentrations up to several ug/L levels has caused concern that these substances might affect non-target organisms in freshwaters. Daphnia sp., a keystone organism in lakes and ponds, is known for diel vertical migration (DVM) and life-history changes (LHCs) as inducible defenses against predation by fish. ...Whether (i) environmentally relevant concentrations of DEET, EBAPP or Icaridine have repellent effects on Daphnia magna and (ii) if these repellents are infodisruptors for DVM and LHCs /was tested/. Using concentrations of up to 44 ug/L, the repellents neither had effects on juvenile somatic growth nor on clutch size. In thermally stratified water columns with a repellent-free hypolimnion, no repellent effects of the test compounds on D. magna were observed. The presence of fish-borne infochemicals induced LHCs, which are characterized by a reduced size at first reproduction, and DVM in D. magna. These effects were not affected by the presence of either repellent. Hence no evidences for infodisruption of the chemical communication of fish and Daphnia by DEET, EBAAP or Icaridine were found.

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of July 7, 2016: http://actor.epa.gov/dashboard/]

Using a structure estimation method based on molecular connectivity indices(1), the Koc of ethyl butylacetylaminopropionate can be estimated to be 36(SRC). According to a classification scheme(2), this estimated Koc value suggests that ethyl butylacetylaminopropionate is expected to have very high mobility in soil.

/HUMAN EXPOSURE STUDIES/ Closed epicutaneous irritation test using 15% a.i. /IR3535/ in aqueous alcohol /was performed in 30 human volunteers. No skin reactions were observed. /From table/

/HUMAN EXPOSURE STUDIES/ Repetitive exposure test using 15% a.i. /IR3535/ in aqueous alcohol /was performed/ in 10 human volunteers 3 wk at twice/wk (induction phase); 12 d break; then 7th application (challenge). No toxic or allergic reactions /were observed/. /From table/

An estimated BCF of 6 was calculated in fish for ethyl butylacetylaminopropionate(SRC), using a log Kow of 1.7(1) and a regression-derived equation(2). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Henry's Law constant for ethyl butylacetylaminopropionate is estimated as 4.6X10-9 atm-cu m/mole(SRC) derived from its vapor pressure, 1.1X10-3 mm Hg(1), and water solubility, 7.0X10+4 mg/L(1). This Henry's Law constant indicates that ethyl butylacetylaminopropionate is expected to be essentially nonvolatile from water and moist soil surfaces(2). Ethyl butylacetylaminopropionate is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).

/LABORATORY ANIMALS: Acute Exposure/ 10% /IR3535/ solution in ethanol /was/ applied to shaven nuchal area of 10 Himalayan white spotted albino guinea pigs. No erythema or edema observed at UV-exposed and unexposed sites. /From table/

/LABORATORY ANIMALS: Acute Exposure/ Mongrel dogs (1 male, 1 female per dose group) /were given/ undiluted /IR3535/ by gavage at 1, 2, 4 and 8 g/kg bw followed by 10 mL water. All animals survived; doses of 2 g/kg bw or more induced vomiting after 30-60 minutes followed by salivation after 20-30 minutes. /From table/

/LABORATORY ANIMALS: Acute Exposure/ Undiluted /IR3535 was/ applied to shaven dorsal skin (6 hr exposure; recovery period 14 d) of Sprague-Dawley rats (5 males, 5 females per dose level); doses 6.35, 7.9, 10.00 mL/kg. Up to 10 mL/kg bw no systemic reactions observed; erythemas at all dose levels, one rat had an erythema of grade 2. /From table/

/LABORATORY ANIMALS: Acute Exposure/ Undiluted /IR3535 was/ applied to shaven dorsal skin (6 hr exposure; recovery period 14 d) beagle dogs (1 male, 1 female per dose level); doses 6.35, 7.9, 10.00 mL/kg. Up to 10 mL/kg bw no systemic reactions observed; local erythemas observed at all doses. /From table/

For more Non-Human Toxicity Excerpts (Complete) data for Ethyl butylacetylaminopropionate (21 total), please visit the HSDB record page.

The rate constant for the vapor-phase reaction of ethyl butylacetylaminopropionate with photochemically-produced hydroxyl radicals has been estimated as 2.9X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 13 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). A base-catalyzed second-order hydrolysis rate constant of 0.058 L/mole-sec(SRC) was estimated using a structure estimation method(1); this corresponds to half-lives of 3.8 years and 140 days at pH values of 7 and 8, respectively(1). Ethyl butylacetylaminopropionate contains chromophores that absorb at wavelengths >290 nm(2) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Occupational exposure to ethyl butylacetylaminopropionate may occur through inhalation and dermal contact with this compound at workplaces where ethyl butylacetylaminopropionate is produced or used. Use data indicate that the general population may be exposed to ethyl butylacetylaminopropionate via inhalation of mist and dermal contact with consumer products containing ethyl butylacetylaminopropionate. (SRC)