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Toxicity Effects

CAS Registry Number: 123-54-6

Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 2.

Names 1

  • 2,4-Dioxopentane
  • 2,4-Pentanedione

Human Toxicity Excerpts

  • CASE REPORTS: ... A case /was reported/ involving an individual who had developed contact dermatitis to Cu(II)-acetyl acetonate and who also showed a cross reaction to 2,4-pentanedione.[Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. 6:175]
  • OTHER TOXICITY INFORMATION: Exposure to 2,4-pentanedione may produce toxicity by the oral, dermal, or inhalation routes. Although ingestion would not appear to be a common route of exposure, accidental ingestion could be lethal or could produce irreversible neurologic impairment. Single high-level exposures dermally or by inhalation should be avoided. Repeated exposures to low concentrations may be cumulative.[Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. 6:172]
  • OTHER TOXICITY INFORMATION: In the patch test study with human volunteers no information was available concerning gender and health status as well as a possible allergic predisposition of the test persons. Of the 12 persons tested three of them showed no, seven doubtful and two a positive reaction after an exposure period of 24 hr. No skin reactions were evident after 48 and 72 hr, respectively. The results observed in the human patch test were interpreted as an irritating rather than a sensitizing effect and it was concluded ... that sensitization might occur more frequently due to prolonged and close skin contact of pads containing the substance[OECD; Screening Information Data Set for 2,4-Pentanedione, CAS #123-54-6 (November, 2001). Available from, as of August 19, 2006: http://www.inchem.org/documents/sids/sids/PENTANEDIONE.pdf]
  • SIGNS AND SYMPTOMS: 2,4-Pentanedione (2 to 14 ppm) has been reported to produce nausea and headaches in several persons, and may have been associated with the occurrence of hives in one worker ...[Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. 6:174]
  • SIGNS AND SYMPTOMS: 2,4-Pentanedione is appreciably more toxic by oral ingestion and vapor inhalation than either 1,2- or 1,4-diketones and saturated monoketones. The acute oral toxicity is high and internal consumption should be avoided. It is comparable in this respect to mesityl oxide. Breathing 2,4-pentanedione vapors may cause dizziness, headache, nausea, vomiting, and loss of consciousness. Skin irritation appears less hazardous. However, eye burns may result from a large application, similar to soap.[Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984., p. V13 930]
  • SIGNS AND SYMPTOMS: ACUTE HAZARDS/SYMPTOMS: Inhalation--Ataxia. Dizziness. Drowsiness. Headache. Labored breathing. Nausea. Vomiting. Skin--MAY BE ABSORBED! Redness. Eyes--Redness. Pain. Ingestion: Diarrhea. Weakness. (further see Inhalation).[IPCS, CEC; International Chemical Safety Card on 2,4-pentanedione. (April, 1997). Available from, as of August 21, 2006: http://www.inchem.org/documents/icsc/icsc/eics0533.htm]
  • SIGNS AND SYMPTOMS: Acute local: irritant 1. 1= slight: causes readily reversible changes which disappear after end of exposure. Acute systemic: inhalation 2. 2= moderate: may involve both irreversible & reversible changes not severe enough to cause death or permanent injury.[Sax, N.I. Dangerous Properties of Industrial Materials. 4th ed. New York: Van Nostrand Reinhold, 1975., p. 1000]
  • SIGNS AND SYMPTOMS: Mild irritant to skin & mucous membranes.[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 13]
  • SIGNS AND SYMPTOMS: The substance irritates the eyes, the skin and the respiratory tract. The substance may cause effects on the nervous system, resulting in tissue lesions. Repeated or prolonged contact may cause skin sensitization. The substance may have effects on the thymus, lungs, central nervous system and nasal passage.[IPCS, CEC; International Chemical Safety Card on 2,4-pentanedione. (April, 1997). Available from, as of August 21, 2006: http://www.inchem.org/documents/icsc/icsc/eics0533.htm]

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Non-Human Toxicity Excerpts

  • ALTERNATIVE and IN VITRO TESTS: ... Rabbit skeletal myofibrils were incubated with /2,4-pentanedione/ to study the alteration of actin in its native state within the myofilament lattice. Preparations of native and desensitized myofibrils were incubated with 100 M/M of actin lysin ... Actin isolated from /2,4-pentanedione/ treated myofibrils contained 0.5 M of enamine/M. In the presence of Ca2+ Mg2+-ATPase activity of /2,4-pentanedione/ treated native myofibrils was 110 to 120% of max Ca2+ stimulated activity in untreated controls ... /It was suggested that/ /2,4-pentanedione/ potentiated "on" state of the myofibrillar ATPase activity ...[European Chemicals Bureau; IUCLID Dataset, Pentane-2,4-dione (CAS No. 123-54-6) (2000 CD-ROM edition). Available from, as of August 21, 2006: http://esis.jrc.ec.europa.eu/] **PEER REVIEWED**
  • ALTERNATIVE and IN VITRO TESTS: ... Hepatic microsomes from phenobarbital-induced male Wistar rats were incubated for 30 min at 30 deg C with 16 mM /2,4-pentanedione/ and a NADPH-generating system ... /2,4-pentane was/ binding to the drug metabolizing enzyme cytochrome P-450 ca 3.0 mM (binding type I, 385 to 420 nM). NADPH oxidation /was/ 1.6 nM/min/mg microsomal protein. Cytochrome P-450 loss 12%. /And/ 0.21% heme ... 92% ... cytochrome b5 and 107% NADPH-cytochrome-c reductase /loss were observed/.[European Chemicals Bureau; IUCLID Dataset, Pentane-2,4-dione (CAS No. 123-54-6) (2000 CD-ROM edition). Available from, as of August 21, 2006: http://esis.jrc.ec.europa.eu/] **PEER REVIEWED**
  • ALTERNATIVE and IN VITRO TESTS: ... Purified membrane-bound NAD glycohydrolase of rabbit erythrocytes was incubated at pH 7.4 with 2 to 20 mM /2,4-pentanedione/ and activity of the enzyme measured for up to 80 min ... /2,4-Pentane/ led to a time-dependent and concn-dependent inhibition of the enzyme. After 80 min at 20 mM /2,4-pentanedione/ the activity was reduced to less than 10% of the initial activity.[European Chemicals Bureau; IUCLID Dataset, Pentane-2,4-dione (CAS No. 123-54-6) (2000 CD-ROM edition). Available from, as of August 21, 2006: http://esis.jrc.ec.europa.eu/] **PEER REVIEWED**
  • ALTERNATIVE and IN VITRO TESTS: ... The human enzyme myeloperoxidase (0.033 units/mL) was incubated in vitro at pH 4.6 with 10 mM /2,4-pentanedione/ ... Carbon-centered radicals (mutagenicity) were detected using the spin-trapping technique. Same results with horseradish peroxidase and chloroperoxidase /were observed/.[European Chemicals Bureau; IUCLID Dataset, Pentane-2,4-dione (CAS No. 123-54-6) (2000 CD-ROM edition). Available from, as of August 21, 2006: http://esis.jrc.ec.europa.eu/] **PEER REVIEWED**
  • ALTERNATIVE and IN VITRO TESTS: Murine erythroleukemia cell line 745 was incubated for 5 days with 3 to 50 mM /2,4-pentanedione/ /2,4-pentanedione/ was quite toxic in the used concn range, but ... was effective in stimulating the induction of hemoglobin production by the cells.[European Chemicals Bureau; IUCLID Dataset, Pentane-2,4-dione (CAS No. 123-54-6) (2000 CD-ROM edition). Available from, as of August 21, 2006: http://esis.jrc.ec.europa.eu/] **PEER REVIEWED**
  • ALTERNATIVE and IN VITRO TESTS: Sea urchin embryos (Arbacia punctulata) were incubated 1 hr after fertilization with ... /pentane-2,4-dione/ for 3 hr and tritiated thymidine added last 2 hr ... The incorporation of thymidine was inversely related to ... /pentane-2,4-dione/ concn; EC50 of 2 different trials: 206 mg/L (95% confidence limits 68 to 561 mg/L), 169 mg/L (81 to 240 mg/L).[European Chemicals Bureau; IUCLID Dataset, Pentane-2,4-dione (CAS No. 123-54-6) (2000 CD-ROM edition). Available from, as of August 20, 2006: http://esis.jrc.ec.europa.eu/] **PEER REVIEWED**
  • ALTERNATIVE and IN VITRO TESTS: Sea urchin embryos (Arbacia punctulata) were incubated at fertilization with ... /pentane-2,4-dione/ for 4 hr and tritiated thymidine added last 2 hr ... Sperm cells of the same species were incubated for 1 hr at 20 deg C with ... /pentane-2,4-dione/ and degree of fertilization measured thereafter ... The incorporation of thymidine (DNA-synthesis) was inversely related to ... /pentane-2,4-dione/ concn; EC50 105.4 mg/L (95% confidence limits 56.5 to 170.3 mg/L) ... EC50 for sperm cell toxicity 0.9 mg/L (95% confidence limit 0.8 to 1.1 mg/L).[European Chemicals Bureau; IUCLID Dataset, Pentane-2,4-dione (CAS No. 123-54-6) (2000 CD-ROM edition). Available from, as of August 20, 2006: http://esis.jrc.ec.europa.eu/] **PEER REVIEWED**
  • ALTERNATIVE and IN VITRO TESTS: Sea urchin embryos (Arbacia punctulata) were incubated at fertilization with ... /pentane-2,4-dione/ for 5 hr and increase in DNA measured by fluorometric determination ... The DNA increase was inversely related to ... /pentane-2,4-dione/ concn; EC50 21.3 mg/L (95% confidence limits 14.6 to 31.1 mg/L).[European Chemicals Bureau; IUCLID Dataset, Pentane-2,4-dione (CAS No. 123-54-6) (2000 CD-ROM edition). Available from, as of August 20, 2006: http://esis.jrc.ec.europa.eu/] **PEER REVIEWED**
  • GENOTOXICITY: ... /An/ Ames test was conducted in Salmonella typhimurium strains TA 92, 98, 100 and 104 in the absence of a metabolic activation system. Water or DMSO served as solvent (negative) controls, potassium dichromate (10 ug/plate), methyl methane sulfonate (2 ug/plate) and hycanthone (20 ug/plate) served as positive controls. No information was given as to the concentration ranges of 2,4-pentanedione used in strains TA92, 98 and 100 where no mutagenic effects were reported. Test concentrations in the strain TA 104 were 1.9 to 48 umol/plate ... /2,4-pentanedione/ was added in water or DMSO (not specified in the reference available) in a volume of 0.1mL. According to the results observed and considering the rates of spontaneous revertants for this particular strain (400 to 700 revertants), 2,4-pentanedione /was/ considered only slightly mutagenic in TA 104 at concentrations ranging from 1.9 to 10 umol/plate, /where/ the number of revertants/plate increased to its maximum of 1500 ... At concentrations > 10 umol/plate, no significant increase in the number of revertants compared to control values could be observed. Thus the increase of revertants/plate was not in a dose-response relationship.[OECD; Screening Information Data Set for 2,4-Pentanedione, CAS #123-54-6 (November, 2001). Available from, as of August 19, 2006: http://www.inchem.org/documents/sids/sids/PENTANEDIONE.pdf] **PEER REVIEWED**
  • GENOTOXICITY: ... Acetylacetone demonstrated a strong mutagenic effect on S-typhimurium (TA-104).[Gava C et al; Toxicol and Environ Chem 22 (1-4): 149-57 (1989)] **PEER REVIEWED**
  • GENOTOXICITY: ... Male Fischer 344 rats, 20 per group, were exposed to 2,4-PD vapor concentrations (mean +/- SD) of 0, 99.1 +/- 2.2, 412 +/- 12.6 and 694 +/- 9.1 ppm, for 6 hr/day for 5 consecutive days. The day following the final exposure they were bred to unexposed female Fischer 344 rats, 2 per week for 8 consecutive weeks. Weight loss occurred with males during 2,4-PD exposure for the 412 and 694 ppm groups, with compensatory increased weight at 694 ppm, for the first two weeks postexposure. ... Minor transient reproductive and gestational effects were present at 412 and 694 ppm. At week 2 there was a reduction, not statistically significant, in the number of corpora lutea and total and viable implants per dam at 694 ppm, and a slight increase in preimplantation loss. At week 3 the number of pregnant females was slightly reduced at 412 and 694 ppm, causing a lowered female fertility index. At week 4 there was a slight reduction in the number of total and viable implants per litter and a significant preimplantation loss at 694 ppm. The dominant lethal factor (FL%) was increased slightly at 694 ppm for weeks 2 and 4. The "no observable effect" level for dominant lethal effects was 99 ppm.[T yl RW et al; Toxicol Ind Health 5 (3): 463-77 (1989)] **PEER REVIEWED** PubMed Abstract
  • GENOTOXICITY: ... Male and female Swiss Webster mice as well as male and female Sprague-Dawley rats (5/sex at the groups for air-only control, positive control, 100 ppm, 400 ppm, 600 ppm) were exposed to 2,4-pentanedione vapor under identical conditions (exposure concentrations 0, 100, 400 and 600 ppm; corresponding to 0; 417; 1,668 and 2,502 mg/cu m, respectively; exposure period 5 days, 6 hr/day) and bone marrow was collected 24 hr after final exposure and examined for the formation of micronucleated polychromatic erythrocytes (PCEs). No statistically significant increases in the incidence of micronucleated PCEs could be found in any of the dose groups administered ...[OECD; Screening Information Data Set for 2,4-Pentanedione, CAS #123-54-6 (November, 2001). Available from, as of August 20, 2006: http://www.inchem.org/documents/sids/sids/PENTANEDIONE.pdf] **PEER REVIEWED**
  • GENOTOXICITY: ... The umu-test was used /to/ detect the induction of DNA repair after incubation /of Salmonella typhimurium TA 1535/pSK1002/ with /40 mg/mL 2,4-pentanedione/ ... at 37 deg C for 2 to 24 hr ... Weakly positive results with and without S-9 metabolic activation after 2 hr incubation, strong positive results with S-9 after 24 hr incubation, /and/ after 4 and 6 hr incubation negative results with and without S-9 /were observed/.[European Chemicals Bureau; IUCLID Dataset, Pentane-2,4-dione (CAS No. 123-54-6) (2000 CD-ROM edition). Available from, as of August 21, 2006: http://esis.jrc.ec.europa.eu/] **PEER REVIEWED**
  • GENOTOXICITY: /In a/ liquid Bacillus subtilis/microsome rec-assay, /2,4-pentanedione showed/ positive result with /and/ negative result without S-9 metabolic activation ...[European Chemicals Bureau; IUCLID Dataset, Pentane-2,4-dione (CAS No. 123-54-6) (2000 CD-ROM edition). Available from, as of August 21, 2006: http://esis.jrc.ec.europa.eu/] **PEER REVIEWED**
  • GENOTOXICITY: /In an/ Escherichia coli reverse mutation assay, the specific activity of /2,4-pentanedione was/ 7.73 revertants/mg with metabolic activation.[European Chemicals Bureau; IUCLID Dataset, Pentane-2,4-dione (CAS No. 123-54-6) (2000 CD-ROM edition). Available from, as of August 21, 2006: http://esis.jrc.ec.europa.eu/] **PEER REVIEWED**
  • GENOTOXICITY: Antimutagenic activity /of 2,4-pentane was reported in 2 assays/ ... a) Ames-test: TA98 bacteria concomitantly exposed to the mutagens 2-naphthohydroxamic acid or 5 to 20 nM 2-nitrofluorene and 0.01 or 0.02 mM /2,4-pentanedione/ for 30 min before plating. b) Rat liver yeast transfer RNA exposed to the carcinogen N-acetoxy-2-acetylaminofluorene with 0.1 to 0.4 mM /2,4-pentanedione/ or without ... for 1 hr at 37 deg C/ ... Reduced number of revertants compared to control /in a) was observed/ ... /2,4-pentanedione/ inhibited concn dependent the binding of the carcinogen to the transfer RNA.[European Chemicals Bureau; IUCLID Dataset, Pentane-2,4-dione (CAS No. 123-54-6) (2000 CD-ROM edition). Available from, as of August 21, 2006: http://esis.jrc.ec.europa.eu/] **PEER REVIEWED**
  • GENOTOXICITY: In a forward-gene-mutation assay (HGPRT-test) 2,4-pentanedione did not cause any statistically significant increases in the incidence of mutations in CHO-cells at the HGPRT-locus both in the presence and absence of a metabolic activation system (liver S-9 mix produced from rats pretreated with Aroclor 1254). The highest substance concentrations in this test were 1.5 and 1.0 mg/mL in the absence and presence of metabolic activation, respectively. The exposure time was 5 hr with and without activation followed by a 9 to 12 days subculturing period to allow expression of the mutant phenotype ... Random cultures with increased mutant values were within the typical range of variability.[OECD; Screening Information Data Set for 2,4-Pentanedione, CAS #123-54-6 (November, 2001). Available from, as of August 20, 2006: http://www.inchem.org/documents/sids/sids/PENTANEDIONE.pdf] **PEER REVIEWED**
  • GENOTOXICITY: In a mouse spermatogonial assay 2,4-pentanedione was administered in deionized water to 6 male NMRI mice at a dose of 800 mg/kg bw and spermatogonial cells of 5 animals/dose prepared 24 and 48 hours after administration ... 100 cells per animal (ie 500 cells per time point) were examined for chromosomal aberrations. Neither a reduction in mitotic indices nor an increase in the number of numerical or structural chromosomal aberrations were detectable in the substance treated group when compared with vehicle treated controls while pronounced effects were caused by adriblastin /the positive control/. 2,4-Pentanedione is considered non-clastogenic to germ cells under the conditions of the assay.[OECD; Screening Information Data Set for 2,4-Pentanedione, CAS #123-54-6 (November, 2001). Available from, as of August 20, 2006: http://www.inchem.org/documents/sids/sids/PENTANEDIONE.pdf] **PEER REVIEWED**
  • GENOTOXICITY: Male and female Swiss Webster mice were exposed to 0 (10 animals per sex), 100 (10 animals per sex), 400 (10 animals per sex) and 600 ppm (14 animals per sex) of 2,4-pentanedione vapour for 5 consecutive days, 6 hr/day by whole body exposure. These concentrations correspond to 0; 417; 1,668 and 2,502 mg/cu m ... In the 600 ppm exposure groups only two females assigned to the bone marrow collection times of 6 hr and 24 hr survived until the scheduled sacrifice ... In all other doses groups no treatment related adverse effects were found. It could be demonstrated that 2,4-pentanedione did not increase the number of chromosomal aberrations in a statistically significant manner ...[OECD; Screening Information Data Set for 2,4-Pentanedione, CAS #123-54-6 (November, 2001). Available from, as of August 20, 2006: http://www.inchem.org/documents/sids/sids/PENTANEDIONE.pdf] **PEER REVIEWED**
  • GENOTOXICITY: The /effect/ ... of 2,4-pentanedione ... was studied ... in male F344 rats by the inhalation route of exposure. Dose ranges included 0, 100, 400 and 700 ppm (corresponding to 0; 417; 1,668 and 2,919 mg/cu m), respectively, and 20 animals per dose group were exposed to test substance vapour for 5 consecutive days, 6 hr/day. After the last exposure treated males were paired with naive females (two females with one male) of the same strain for eight consecutive weeks and observed for evidence of copulation. Females without evidence of breeding (copulation plug or vaginal smear) were removed and replaced weekly. After eight weeks brains, testes as well as thymus of males were removed for histopathological examination. Males exposed to 400 and 700 ppm test substance showed reduced body weights at week 1 and only males of the highest exposure group still showed reduced body weights one week after termination of exposure. Due to stress by inhalation exposure weight loss was evident in animals of all dose groups. No treatment related clinical signs of toxicity and no microscopic lesions were found on histological examination of brain, testes and thymus in any of the exposure groups. Signs of toxicity were restricted to males of the 700 ppm only and included aggression, red ocular discharge and red perioral encrustation. Reproductive parameters for males and females were affected only on week 3 where the number of pregnant females was slightly reduced at 400 and 700 ppm resulting in a lowering of the female fertility index. Gestational parameters were affected on weeks 2 and 4 of mating and characterised by a reduction of the corpora lutea per dam in week 2 and a reduction in the number of total and viable implants per dam both in week 2 and 4 at 700 ppm. In week 2 postimplantation loss was slightly but not statistically significantly increased at 400 and 700 ppm and preimplantation loss was significantly increased in week 4. Although there was weak statistical significance of the 700 ppm value, the very high standard deviation in both cases indicates high variability of the data from individual animals.[OECD; Screening Information Data Set for 2,4-Pentanedione, CAS #123-54-6 (November, 2001). Available from, as of August 20, 2006: http://www.inchem.org/documents/sids/sids/PENTANEDIONE.pdf] **PEER REVIEWED**
  • GENOTOXICITY: The ability of 2,4-pentanedione to induce chromosomal aberrations was investigated in cytogenetic tests using CHO-cells both in the presence and absence of a metabolic activation system (liver S-9 mix produced from rats pretreated with Aroclor 1254) ... The highest test substance concentrations ... were 0.12 mg/mL and 0.14 mg/mL in the absence and presence of metabolic activation and did not produce excessive cytotoxicity. Exposure times of cells towards test substance were 2 hr and 6 hr with and without metabolic activation, respectively. In the absence of S-9 activation a test substance related increase in the number of chromosomal aberration was observable as indicated by chromosome breakage, while in the presence of activation ... no clastogenicity was found under the conditions of the experimental procedure.[OECD; Screening Information Data Set for 2,4-Pentanedione, CAS #123-54-6 (November, 2001). Available from, as of August 20, 2006: http://www.inchem.org/documents/sids/sids/PENTANEDIONE.pdf] **PEER REVIEWED**
  • GENOTOXICITY: The capability of 2,4-pentanedione to induce micronuclei was investigated in male and female Sprague-Dawley rats after ip admin ... Five animals per sex and dose were used in this study and a total of five dose groups (50, 100, 200, 400 and 650 mg/kg bw, corresponding to 6.5, 13, 26, 52, and 86 % of the oral LD50, respectively) was administered to the animals as a single ip injection ... 2,4-Pentanedione did not produce statistically significant, treatment related increases in the incidence of micronucleated polychromatic erythrocytes in male and female Sprague-Dawley rats as assessed at 6, 24 and 48 hours.[OECD; Screening Information Data Set for 2,4-Pentanedione, CAS #123-54-6 (November, 2001). Available from, as of August 20, 2006: http://www.inchem.org/documents/sids/sids/PENTANEDIONE.pdf] **PEER REVIEWED**
  • GENOTOXICITY: The genotoxicity of 2,4-pentanedione was studied ... using mammalian cells (CHO cells) /to investigate/ ... sister chromatid exchanges (SCE) ... 2,4-Pentanedione produced a statistically significant increase in the number of SCE/cell at concentrations not causing overt cytotoxicity both in the presence and absence of a metabolic activation system (liver S-9 mix produced from rats pretreated with Aroclor 1254). Highest test substance concentrations employed in this test were 0.1 and 0.3 mg/mL and exposure times were 5 hr and 2 hr in the absence and presence of a metabolic activation system, respectively. Additionally, it was found that 2,4-pentanedione was considered genotoxic particularly in the absence of metabolic activation since the magnitude of SCE induction was lower when activation by S9 mix was included.[OECD; Screening Information Data Set for 2,4-Pentanedione, CAS #123-54-6 (November, 2001). Available from, as of August 20, 2006: http://www.inchem.org/documents/sids/sids/PENTANEDIONE.pdf] **PEER REVIEWED**
  • GENOTOXICITY: The mutagenicity of 2,4-pentanedione was investigated in a standard Ames test using Salmonella typhimurium strains TA 98, 100, 1535, 1537 and 1538 both in the presence and absence of a metabolic activation system (liver S-9 mix produced from rats pretreated with Aroclor 1254) ... A statistically significant increase in the revertants/plate (less than doubling) /was not observed/ thereby demonstrating no potential of 2,4-pentanedione to induce gene mutations.[OECD; Screening Information Data Set for 2,4-Pentanedione, CAS #123-54-6 (November, 2001). Available from, as of August 19, 2006: http://www.inchem.org/documents/sids/sids/PENTANEDIONE.pdf] **PEER REVIEWED**
  • GENOTOXICITY: The potential of 2,4-pentanedione to induce micronuclei was investigated in male and female Swiss Webster mice after ip admin. Five mice per sex and dose group were used, doses administered were 0, 200, 400 and 650 mg/kg bw corresponding to 25, 50, and 80% of the ip LD50, respectively. A negative (water) and a positive control (triethylenemelamine) was included in this assay. Blood samples were taken 30, 48 and 72 hr after treatment with 2,4-pentanedione for the evaluation of micronucleated polychromatic erythrocytes (PCEs) while blood samples from positive controls animals were subjected to PCE analysis after 30 hr only. At 30 and 48 hr, respectively, a statistically significant increase in the number of micronucleated PCEs was detectable in a dose dependent manner while the number of PCEs with micronuclei was not different from controls in the 72 hr blood samples ... In conclusion 2,4-pentanedione induces micronuclei in mice of both sexes after administration by the ip route.[OECD; Screening Information Data Set for 2,4-Pentanedione, CAS #123-54-6 (November, 2001). Available from, as of August 20, 2006: http://www.inchem.org/documents/sids/sids/PENTANEDIONE.pdf] **PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: ... 30 min was the maximum time that rats could be exposed to a saturated atmosphere of 2,4-pentanedione vapor before death occurred. The same level was lethal to all animals exposed for 1 hr.[Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. 6:173] **PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: ... Five /Sprague-Dawley rats/ ... per sex and dose were used ... and a total of five dose groups (50, 100, 200, 400 and 650 mg/kg bw, corresponding to 6.5, 13, 26, 52, and 86% of the oral LD50, respectively) was administered to the animals as a single ip injection. The two lowest dose groups of 50 and 100 mg/kg were included because of mortalities in the 400 and 650 mg/kg dose groups. Substance related signs of toxicity in the 400 and 650 mg/kg groups included hypoactivity, incoordination, prostration, whole body tremor, tonic convulsions, excessive vocalization, urogenital area wetness, labored respiration, gasping, perinasal and perioral wetness, nasal discharge, periocular encrustation and lacrimation. In the other dose groups no (50 and 100 mg/kg bw) or less pronounced (200 mg/kg bw) signs of toxicity were reported ...[OECD; Screening Information Data Set for 2,4-Pentanedione, CAS #123-54-6 (November, 2001). Available from, as of August 20, 2006: http://www.inchem.org/documents/sids/sids/PENTANEDIONE.pdf] **PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: /2,4-pentanedione is/ slightly irritating /to rabbit skin/ ... 0.01 mL /2,4-pentanedione/ applied /uncovered/ to the same spot on the clipped skin of the belly of 5 rabbits, 3 times/day for 3 days ... After 3 applications 3/5 animals ... /showed/ moderate to marked capillary injection, after 6 applications moderate erythema in 1/5, moderate capillary injection on 3/5, 1/5 negative, same results after 9 applications.[European Chemicals Bureau; IUCLID Dataset, Pentane-2,4-dione (CAS No. 123-54-6) (2000 CD-ROM edition). Available from, as of August 21, 2006: http://esis.jrc.ec.europa.eu/] **PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: 2,4-Pentanedione applied to the depilated abdomens of guinea pigs under an occlusive wrap for 24 hr produced moderate skin irritation ... Four guinea pigs receiving 20 mL/kg under a wrap died within 24 to 72 hr of application ... but only one of five guinea pigs showed a weak sensitization reaction ...[Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. 6:172] **PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: A skin irritation study was conducted in New Zealand White rabbits. A volume of 0.5 mL of undiluted /2,4-pentanedione/ ... was applied on the dorsal skin of six rabbits (three males and three females, respectively) for 4 hr with occlusive dressing. Treated skin areas were inspected 1 hr and 1, 2, 3, 7 and 14 days after removal of the dressing ... One hr after removal of the occlusive dressing slight erythema were detectable in 5/6 animals (3 males and 2 females) ... After 24 hr erythema were detectable in 6/6 animals ... 1 hr after removal of the occlusive dressing slight and moderate edema formation was observable in 5/6 and 1/6 rabbits ... respectively; after 24 hr slight edema were still present in 5/6 rabbits ... After 48 and 72 hr 5 and 3 animals revealed just detectable erythema ... Mild edema were observable at 48 and 72 hr in 2 and 1 animals, respectively ... With the exception of mild desquamation detectable in 5/6 animals no skin irritations or other effects were present on day 7 ... The substance was overall evaluated as not irritating to the skin of rabbits.[OECD; Screening Information Data Set for 2,4-Pentanedione, CAS #123-54-6 (November, 2001). Available from, as of August 19, 2006: http://www.inchem.org/documents/sids/sids/PENTANEDIONE.pdf] **PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: After inhalation in Wistar rats (4 hs; 628, 919, 1231 and 1508 ppm, respectively, corresponding to 2,619; 3,832; 5,133 and 6,288 mg/cu m) mortalities were observable in animals of the two highest dose groups. Signs of toxicity included reduced reflexes, respiratory difficulties, tremor as well as periocular, perioral and perinasal wetness and encrustation. The combined LC50-value ... was determined to be 1224 ppm (5.1 mg/L/4hr) ...[OECD; Screening Information Data Set for 2,4-Pentanedione, CAS #123-54-6 (November, 2001). Available from, as of August 19, 2006: http://www.inchem.org/documents/sids/sids/PENTANEDIONE.pdf] **PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: After oral administration to Wistar rats signs of toxicity were characterized by sluggishness, tremors, kyphosis, lacrimation, unsteady gait, comatose appearance and prostration. On histopathology cervical lymph nodes in most animals were enlarged. The LD50-values determined in females and males in this investigation were 570 and 760 mg/kg ...[OECD; Screening Information Data Set for 2,4-Pentanedione, CAS #123-54-6 (November, 2001). Available from, as of August 19, 2006: http://www.inchem.org/documents/sids/sids/PENTANEDIONE.pdf] **PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: High doses of 2,4-pentanedione produce dyspnea, severe central nervous system depression, and death in experimental animals. Similar clinical effects are produced by lower repeated doses, except that some animals survive and develop a central nervous system disorder characterized by an irreversible cerebellar syndrome. Thymic necrosis and atrophy may accompany central nervous system damage in experimental animals. Slight decreases in male fertility have been reported in experimental animals with exposure to 2,4-pentanedione.[Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. 6:172] **PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: The LD50 of an acute dermal toxicity study after application of undiluted 2,4-pentanedione to the shaved skin of rabbits was in the range of 790 and 1,370 mg/kg bw for female and male animals, respectively. Signs of systemic toxicity were characterised by salivation, dilated pupils and convulsions. In dead animals red mottled lungs and congestion of the tracheal mucosa were observable. Local effects comprised erythema, edema, scab formation and necrosis.[OECD; Screening Information Data Set for 2,4-Pentanedione, CAS #123-54-6 (November, 2001). Available from, as of August 19, 2006: http://www.inchem.org/documents/sids/sids/PENTANEDIONE.pdf] **PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: The eye irritation potential of 2,4-pentanedione was investigated in rabbits. A volume of 0.1mL of undiluted /2,4-pentanedione/ ... was applied to the eyes of 6 female New Zealand White rabbits. Eyes were inspected 1, 4, 24, 48 and 72 hr as well as 7 days post-instillation, respectively ... Opacities of the cornea were not detectable at any time. One hr after application of the material, slight redness of the conjunctivae was observable in 5/6 animals ... slight and moderate chemosis in 2/6 and 1/6 animals ... respectively, slight and moderate discharge in 2/6 and 3/6 animals ... respectively, and slight inflammation of the iris in 2/6 animals ... Four hours after application of the material, slight inflammation of the iris was evident in 1/6 animals ... slight redness of the conjunctivae in 4/6 animals ... slight and moderate chemosis in 2/6 and 1/6 animals ... respectively, slight and moderate conjunctival discharge was observable in 3/6 and 2/6 animals ... respectively. Twenty-four hr postinstillation all effects seen were completely reversible ... The material resulted in minor transient irritation with no corneal involvement ...[OECD; Screening Information Data Set for 2,4-Pentanedione, CAS #123-54-6 (November, 2001). Available from, as of August 19, 2006: http://www.inchem.org/documents/sids/sids/PENTANEDIONE.pdf] **PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: In a subchronic inhalation study conducted in male and female F344 rats after exposure to 0, 100, 300 and 650 ppm (nominal concentrations, corresponding to 0; 417; 1,217 and 2,711 mg/cu m) no findings of pathological significance were noted in testes and epididymis of males as well as in uterus, cervix and ovaries of females on comparison with untreated control animals both immediately after study termination and after a four week recovery period, respectively, thereby revealing no adverse effects on male and female reproductive organs ... One/10 animals each of the control and intermediate dose group (300 ppm) had changes in uterus size ("luminal ectasia") while 1/10 animals of the intermediate dose group (300 ppm) had size changes in the cervix ("luminal ectasia") ... NOAEL and LOAEL were 100 and 650 ppm, respectively. The NOAEL for effects on gonadal tissues was 650 ppm.[OECD; Screening Information Data Set for 2,4-Pentanedione, CAS #123-54-6 (November, 2001). Available from, as of August 20, 2006: http://www.inchem.org/documents/sids/sids/PENTANEDIONE.pdf] **PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: The developmental toxicity of 2,4-pentanedione was studied ... by exposing timed pregnant Fischer 344 rats to /its vapors/ ... on gestational days 6 to 15 inclusive to analytically measured concentrations (as mean + or - SD) of 53 + or - 1.6, 202 + or - 4.7 and 398 + or - 5.7 ppm. At sacrifice (gestational day 21) fetuses were examined for external, visceral and skeletal variations and malformations. There was no maternal mortality, and body weight was reduced only at 398 ppm. Histological examination of maternal brains from the 398 ppm group showed no abnormalities. No treatment related effects were seen on the number of coropra lutea; total, nonviable or viable implants per litter, pre- or post-implantation losses or fetal sex ratio. Reduced fetal body weight per litter was seen at 398 ppm (males and females and all fetuses) and 202 ppm (males and all fetuses). There was no concentration related or statistically significant, increase in the incidence of individual malformations, malformations by category (external, visceral or skeletal), or total malformations. Partial fetal atelectasis was increased at 398 ppm, and the increased incidence of 17 skeletal variants (out of 79 observed) indicated a consistent pattern of fetotoxicity at 398 ppm.[Tyl Rw et al; Toxicol Ind Hlth 6 (3-4): 461-74 (1990)] **PEER REVIEWED** PubMed Abstract
  • LABORATORY ANIMALS: Neurotoxicity: /2,4-Pentanedione were admin/ sc /to/ 6 ... /male/ Donryu rats ... /at/ 200 mg/kg/day once daily, 5 days/wk /for/ 15 wk ... Moderate effects on body weight gain /were observed/, 4/6 rats showed increased salivation on the 15th day ... and disturbances in gait on the 45th day. Thereafter, all 6 rats developed spastic paralysis of the hind limbs. Significantly reduced motor conduction velocity and sensory conduction velocity (neurophysiological measurement in the rat tail) in the 8 to 10 wk stage of experiment /were observed/ ... /Purity > 97%/[European Chemicals Bureau; IUCLID Dataset, Pentane-2,4-dione (CAS No. 123-54-6) (2000 CD-ROM edition). Available from, as of August 21, 2006: http://esis.jrc.ec.europa.eu/] **PEER REVIEWED**
  • LABORATORY ANIMALS: Neurotoxicity: A dose of 250 mg/kg twice a day by gavage was lethal /to rats/ within 4 days. A dose of 150 mg/kg given twice daily produced head tilt and increased muscle tone in one animal. Another animal developed extreme weakness and tremors. The dose was lowered to 100 mg/kg and treatment continued for 6 wk without any adverse effects. After 6 wk, the dose was increased to 125 mg/kg twice daily. One of four animals developed quadraparesis. Histologic examination of the brain from all treated animals indicated that acute changes were characterized by perivascular edema, hemorrhage into the Virchow-Robbin spaces, and endothelial cell swelling, all primarily localized in the brainstem and cerebellum. Chronic central nervous system lesions were also present as bilateral, symmetrical areas of malacia and gliosis centered on the cerebellar peduncles, olivary nuclei, and lower brainstem.[Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. 6:173] **PEER REVIEWED**
  • LABORATORY ANIMALS: Neurotoxicity: A series of studies was made to clarify the relationship of the chemical structures of 2,3-butanedione (2,3-BDione), 2,4-pentanedione (2,4-PDione) and 2,5-hexanedione (2,5-HDione) to neurotoxicity in terms of n-hexane neuropathy and relative neurotoxic potentials, using electrophysiological methods. These compounds are all molecularly symmetrical diketones with 4, 5 and 6 carbons respectively. A 200 mg/kg dose of each compound was administered subcutaneously five days a week to one of three groups of eight rats. This program continued for 40 weeks in the case of 2,3-BDione and 2,4-PDione and for 14 weeks in the case of 2,5-HDione. Electrophysiological studies of the effects of the compounds on the peripheral nerve were performed by measuring maximum motor conduction velocities (MCV) and sensory conduction velocities (SCV) in the tail nerve of the rats. Residual latencies (RL), motor distal latencies (DL), amplitudes of the muscle action potentials (MAP), and amplitudes of the nerve action potentials (NAP) were also estimated. A significant slowing of MCV began to be observed in the 2,5-HDione group at the 6th week and in the 2,4-PDione group at 10th week. At 8th week, a significant decrease in SCV was also observed in these two groups. The degree of reduction in both MCV and SCV was more pronounced in the 2,5-HDione group than in the 2,4-PDione group. In the 2,5-HDione group, the MCV values were more strongly affected than the SCV values. On the other hand, in the 2,4-PDione group the SCV values were slowed more than the MCV values. The amplitudes of MAP and NAP in the 2,5-HDione group decreased significantly at 12th week and at 10th week, respectively. In the 2,4-PDione group, a significant decrease in NAP amplitudes was observed at 16th week and that in MAP amplitudes at 28th week. The 2,3-BDione group showed a decrease in MAP amplitudes at 28th week. The RL and DL were markedly prolonged at an early stage only in the 2,5-HDione group. The gamma-diketone of 6, 7 and 8 normal chains of the aliphatic hydrocarbons has been reported to cause peripheral distal axonopathy with giant axonal degeneration. This disorder is named gamma-diketone neuropathy. In this study, neurotoxic evidence was revealed by 2,4-PDione, which is 5-carbon and symmetrical beta-diketone.[Nagano M et al; Sngyo Igaku 25 (6): 471-82 (1983)] **PEER REVIEWED** PubMed Abstract
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: ... A dosage-related skin irritation was seen macroscopically and by light microscopy, which was minimal at the low dosage. Mortalities occurred at the mid (1/6 males, 3/6 females) and high dosages (5/12 males, 7/12 females), with deaths between the 2nd and 5th dosing day. ... Signs at the mid and high dosage included hypoactivity, tremors, convulsions, uncoordinated movements and prostration, and appeared between the 2nd and 4th dose. Body weight gain and food consumption were reduced for the mid and high dosage groups. ... Immune effects included decreased lymphocyte counts and lymphoid necrosis in spleen and thymus. Central neuropathology in the mid and high dosages was seen as hemorrhages and neuronal degeneration, the latter principally in piriform cortex, globus pallidus and hippocampus.[Ballantyne B; Vet Hum Toxicol 43 (1): 14-8 (2001)] **PEER REVIEWED** PubMed Abstract
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: ... Groups of two male New Zealand rabbits were administered 250, 500, or 1000 mg/kg of 2,4-pentanedione once a day for 5 days/wk by gavage ... At 1000 mg/kg, both rabbits died within 24 hr after a single dose. At autopsy, rabbits at the 1000 mg/kg level showed congestion of the brain, lungs, and thymus. Histologically, both rabbits at the 1000-mg/kg level showed congestion and hemorrhage in the thymus and in one of the rabbits the thymus was very small. At 500 mg/kg, one rabbit died on the ninth day of the study, and the second rabbit died on the twelfth day following severe central nervous system depression. Gross changes in one rabbit at 500 mg/kg included hemorrhage in the brain, an atrophic thymus, pulmonary congestion, and gastric mucosal hemorrhages. Both rabbits in the 500 mg/kg group showed congestion of the brain. Hemorrhage into the spinal cord was observed in one rabbit, and the one rabbit in which the thymus and stomach were examined showed hemorrhage into the mediastinal fat, marked thymic atrophy with heavy macrophage infiltration, and gastric mucosal hemorrhage. One rabbit receiving 250 mg/kg survived 14 days. Gross changes in rabbits at 250 mg/kg were absent. Animals in the 250 mg/kg group showed no compound-related histologic lesions.[Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. 6:173] **PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: An inhalation study in male and female F344 rats applied a two weeks exposure regimen with inclusion of a two days non-exposure period, ie a total of 9 exposures (5 days and 4 days). Nominal concentrations were 0, 200, 400 and 800 ppm (corresponding to 0; 834; 1,668 and 3,336 mg/cu m) of 2,4-pentanedione vapour, respectively, and test substance concentrations were metered every 33 minutes throughout the exposure period. No substance related mortalities were found in any of the exposure groups. Body weight gains were reduced in either sex of the 800 ppm group and in males only of the 400 ppm group (2 to 4%) while in the 200 ppm group no differences from control body weight gains were detectable. Absolute organ weights were reduced in the 800 ppm group for brain, liver, kidneys, lungs/bronchi and thymus. Relative thymus weights were decreased in the 800 ppm males and females. In the 400 ppm group thymus weights in male animals only were lowered (15 % absolute, 11% relative) and no differences from controls were found in the lowest exposure group of 200 ppm. At 800 ppm leucocytosis in both sexes and a statistically significant increase in lymphocyte count, increased mean corpuscular hemoglobin concentration and mean corpuscular hemoglobin in male rats were detected. Hemoglobin alterations were considered not to be toxicologically significant. No differences from control animals were found for hematological parameters in the 200 and 400 ppm exposure group, respectively. On histopathological examination no gross lesions were observable in any of the exposure groups. A dosage related irritation, manifested as inflammation, congestion and superficial necrosis of the upper respiratory tract, was observed in all 2,4-pentanedione treated groups. Necrosis of the nasal mucosa was frequently observed in the 800 ppm group, occasionally in the 400 ppm group and absent in the 200 ppm group. The degree of mucosal epithelial vacuolisation and lymphocytic infiltration in the submucosa appeared exposure-related. No lesions were found in the lower respiratory tract. Based on the reduction of thymus weights in males of the 400 ppm exposure group the NOAEL and LOAEL of the study is defined to be 200 and 400 ppm, respectively, corresponding to 288.2 mg/kg bw/day and 576.4 mg/kg bw/day assuming a respiratory minute volume of 0.24 L/min (14.4 L/hr) and an average weight of 250 g/rat.[OECD; Screening Information Data Set for 2,4-Pentanedione, CAS #123-54-6 (November, 2001). Available from, as of August 19, 2006: http://www.inchem.org/documents/sids/sids/PENTANEDIONE.pdf] **PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: Fischer-344 rats, in groups of 10 males and 10 females, were exposed for 9 days (6 hr/day) to 2,4-pentanedione (2,4-PD) vapor at mean concentrations of 805, 418, 197, and 0 (control) ppm. No deaths occurred, and the only adverse signs were of sensory irritation (partial closure of eyelids, periocular and perioral wetness) at 805 ppm. Also at 805 ppm were decreased body and organ weights, lymphocytosis, and moderate inflammation of the nasal mucosa. At 418 ppm there was a decrease in body weight gain and mild inflammation of the nasal mucosa. Apart from minimal nasal mucosal inflammation, there were no effects at 197 ppm. In the subchronic (14-week) study, rats were exposed (6 hr/day; 5 days/week) to 650, 307, 101, and 0 (control) ppm of 2,4-PD vapor, using groups containing 20 males and 20 females, with half being sacrificed at the end of the exposure period and the remainder kept for a 4-week postexposure recovery period. An additional 10 males were added to the 650 and 0 ppm groups for glutaraldehyde perfusion and subsequent electron microscopic examination of sciatic nerves. At 650 ppm, all females and 10 of 30 males died between the second and sixth weeks of exposure. These animals had acute degenerative changes in the deep cerebellar nuclei, vestibular nuclei and corpora striata, and acute lymphoid degeneration in the thymus. Seven of 15 male survivors of the 650 ppm group (combined 14-week and recovery sacrifices) had gliosis and malacia in the same brain regions, minimal squamous metaplasia in the nasal mucosa, decreased body and organ weights, lymphocytosis, and minor alterations in serum and urine chemistries. No ultrastructural evidence of peripheral neuropathy was observed. Except for central neuropathy, many of the adverse effects at 650 ppm were less marked in the 4-week recovery animals. No deaths occurred at 307 ppm, but females had slightly decreased body weight gains, and in both sexes there were minor alterations in hematology, serum chemistry, and urinalysis parameters, which were not present in the 4-week recovery animals. Rats exposed to 101 ppm showed no differences from the control rats. Subchronic exposure to 650 ppm of 2,4-PD vapor causes serious adverse biological effects. Under these study conditions, the minimum-effects concentration was 307 ppm, and the no-adverse effects concentration was 101 ppm.[Dodd DE et al; Fundam Appl Toxicol 7 (2): 329-39 (1986)] **PEER REVIEWED** PubMed Abstract
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: In a 14 weeks inhalation study 20 male and 20 female F344 rats per dose were exposed to 0, 100, 300 and 650 ppm (nominal concentrations, corresponding to 0; 417; 1,217 and 2,711 mg/cu m) of 2,4-pentanedione vapour for 6 hr/day, 5 days/wk. 10 animals per sex and dose group were included for a four weeks recovery period and additional 10 animals were added to the control and high dose group for glutaraldehyde perfusion and subsequent examination of sciatic nerves. Test substance concentrations were monitored every 33 minutes during the daily 6 hr exposure. In the 650 ppm group all females and one third of the males died during the 2nd and 6th week. In this dose group several clinical abnormalities such as lacrimation, ataxia, hypoactivity and hypothermia were observable. Surviving animals of the 650 ppm group showed decreased body weight gains, decreased absolute organ weights (brain, liver, kidney, heart, lungs), but increased relative organ weights, and minor alterations in hematology (ie reduced hematocrit and red blood cell counts, increased mean corpuscular hemoglobin and volume and increased lymphocytes), serum chemistry and urinary chemistry. On (histo)-pathological examination acute degeneration in the deep cerebellar and vestibular nuclei, in the corpora striata and acute lymphoid degenerations in the thymus were noteworthy lesions in dead animals of the 650 ppm exposure group. Survivors of this exposure group had gliosis and malacia in the same brain regions but no peripheral neuropathy, minimal squamous metaplasia in the nasal mucosa, and lymphocytosis. Most of the observable substance related effects in the 650 ppm group decreased in frequency and severity during the four weeks recovery period in surviving animals. In the 100 ppm group there were no substance related mortalities in either sex and on comparison with untreated controls no differences in clinical and urinary chemistry, hematology or after histopathological examination were detectable. In the 300 ppm group minor alterations in haematology, serum (serum calcium) and urine chemistry were observable in rats of both sexes while slight decreases in body weight gains (final body weight 5 % decreased) were found in females of this dose group only. All effects in this dose group were completely reversible during the four weeks recovery period and no statistically significant differences between absolute body weight means for controls and the 300 ppm group were observable. Consequently, based on the reversibility of effects in the 300 ppm group the NOAEL, LOEL and LOAEL of this study is defined to be 100 ppm (417 mg/cu m), 300 ppm (1,217 mg/cu m) and 650 ppm (2,711 mg/cu m), respectively. These doses can be converted to a NOAEL of 144.1 mg/kg bw/day, a LOEL of 432.3 mg/kg bw/day and a LOAEL of 936.7 mg/kg bw/day assuming a respiratory minute volume of 0.24 L/min (14.4 L/hr) and an average weight of 250 g/rat.[OECD; Screening Information Data Set for 2,4-Pentanedione, CAS #123-54-6 (November, 2001). Available from, as of August 19, 2006: http://www.inchem.org/documents/sids/sids/PENTANEDIONE.pdf] **PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: In the oral study, doses given by gavage to rats (5 animals per group, strain and sex not specified) were 0, 100, 500 and 1,000 mg/kg bw, respectively ... /2,4-pentanedione/ was administered for 1 to 15 days in 1 to 11 applications. In the highest dose group all animals died within 1 hour after dosing. In the 500 mg/kg bw group 3/5 animals died and 2/5 were sacrificed due to poor condition after four applications. Various substance related systemic effects were observable in this dose group such as distended bladder, congested lungs, clouding of cornea, thymic necrosis, hepatocyte swelling and congestion, nephrosis, lymphadenitis of mesenteric lymph nodes and inflammation of the heart. In the lowest dose group (100 mg/kg bw) no histopathological or gross pathological changes and no differences in weight gain, organ weights, hematology, clinical chemistry or clinical signs were evident. The lowest dose of 100 mg/kg bw was applied 10 times over a 14 days period. According to the results of this study a NOAEL of 100 mg/kg bw could be derived.[OECD; Screening Information Data Set for 2,4-Pentanedione, CAS #123-54-6 (November, 2001). Available from, as of August 19, 2006: http://www.inchem.org/documents/sids/sids/PENTANEDIONE.pdf] **PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: Male and female Fischer 344 rats were exposed to 2,4-pentanedione (2,4-PD) vapor acutely (4 hr) at 1265 or 1811 ppm, or for 6 h day-1, 5 days a week for 14 weeks to 0, 101, 307 or 650 ppm. Mortality occurred within a few hr of the acute exposures (10% at 1265 ppm; 70% at 1811 ppm). All female rats (20) and 10 of 30 male rats exposed to 650 ppm 2,4-PD vapor died by the 38th study day (29 exposures). Twenty-five of the 30 animals that died, and seven of the 15 males that survived, had light microscopical evidence of degenerative lesions, principally within the caudate/putamen nuclei, nuclei of the cerebellar medulla, and vestibular nuclei. Less frequently involved, in animals that died, were various regions of the cerebral cortex. The early histopathological lesions, seen from the 16th study day (12 exposures) to the 38th study day (28 exposures) were characterised by malacia. When present, lesions in male rats surviving the 14-weeks of 650 ppm 2, 4-PD exposure were characterised by malacia and gliosis. ... Neither mortality nor neuropathology were seen in rats subchronically exposed to 101 or 307 ppm, 2,4-PD vapour.[Garman RH; Hum Exp Toxicol 14 (8): 662-71 (1995)] **PEER REVIEWED** PubMed Abstract
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: Male and female New Zealand White rabbits were treated dermally under occluded conditions with doses of 244, 975 and 1,463 mg/kg bw, respectively, for 9 days (5 days first week and 4 days second week). Six animals/sex/group were used in the low and mid dose group, 12 animals/sex/group in the control and high dose group. Application of 1,463 mg/kg bw resulted in death of approx. 50 % of animals of either sex while in the mid dose group 1/6 males and 3/6 females died. Beside local skin irritating effects evident in all dose groups such as acanthosis, subcutaneous edema, dermatitis, hemorrhage, congestion and/or necrosis, only in the mid and high dose group systemic toxicity was observable and characterised by hypoactivity, prostration, salivation, tremors, gasping, convulsions and cyanosis as derived from blue cutis of the nasal area. Pathological examination of the mid and high dose animals identified the brain as a target with hemorrhage and neuronal degeneration in several sections of this organ. On both day 4 and 12, the thymus or thymic region, spleen and/or lymph nodes of several animals of both sexes from the mid and high dose groups were congested and/or hemorrhaged; some animals also had lymphoid depletion/necrosis ... Combined with decreased lymphocyte and eosinophil counts in the high dose group at day 4, possible effects on the immune system /was suggested/. Since the animals from the mid and high dose group had severe skin irritation and many signs of systemic effects a definitive conclusion regarding a treatment related response to the immune system is not possible. In contrast, no substance related differences from controls were reported in the low dose group. According to the systemic effects observed 244 mg/kg bw and 975 mg/kg bw correspond to the NOAEL and LOAEL of this dermal study, respectively.[OECD; Screening Information Data Set for 2,4-Pentanedione, CAS #123-54-6 (November, 2001). Available from, as of August 19, 2006: http://www.inchem.org/documents/sids/sids/PENTANEDIONE.pdf] **PEER REVIEWED**

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • LC50 Fischer rat /inhalation/ 114 ppm/4 hr[Ballantyne B et al; Drug Chem Toxicol 9 (2): 133-46 (1986] **PEER REVIEWED**
  • LC50 Rat inhalation 1224 ppm/4 hr (5.1 mg/L/4 hr)[OECD; Screening Information Data Set for 2,4-Pentanedione, CAS #123-54-6 (November, 2001). Available from, as of August 19, 2006: http://www.inchem.org/documents/sids/sids/PENTANEDIONE.pdf] **PEER REVIEWED**
  • LD50 Mouse ip 750 mg/kg[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 37] **PEER REVIEWED**
  • LD50 Mouse oral 951 mg/kg[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 37] **PEER REVIEWED**
  • LD50 Rabbit (female) dermal 790 mg/kg[OECD; Screening Information Data Set for 2,4-Pentanedione, CAS #123-54-6 (November, 2001). Available from, as of August 19, 2006: http://www.inchem.org/documents/sids/sids/PENTANEDIONE.pdf] **PEER REVIEWED**
  • LD50 Rabbit (male) dermal 1,370 mg/kg[OECD; Screening Information Data Set for 2,4-Pentanedione, CAS #123-54-6 (November, 2001). Available from, as of August 19, 2006: http://www.inchem.org/documents/sids/sids/PENTANEDIONE.pdf] **PEER REVIEWED**
  • LD50 Rabbit percutaneous 810 mg/kg[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 37] **PEER REVIEWED**
  • LD50 Rat (female) oral 570 mg/kg[OECD; Screening Information Data Set for 2,4-Pentanedione, CAS #123-54-6 (November, 2001). Available from, as of August 19, 2006: http://www.inchem.org/documents/sids/sids/PENTANEDIONE.pdf] **PEER REVIEWED**
  • LD50 Rat (male) oral 760 mg/kg[OECD; Screening Information Data Set for 2,4-Pentanedione, CAS #123-54-6 (November, 2001). Available from, as of August 19, 2006: http://www.inchem.org/documents/sids/sids/PENTANEDIONE.pdf] **PEER REVIEWED**
  • LD50 Rat oral 1,000 mg/kg[Verschueren, K. Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. John Wiley & Sons. New York, NY. 2001, p. 1741] **PEER REVIEWED**
  • LD50 Rat oral 55 mg/kg[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 37] **PEER REVIEWED**

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Absorption, Distribution And Excretion

  • 2,4-Pentanedione (2,4-PD; CAS No. 123-54-6), was investigated for its comparative pharmacokinetics in male Fischer 344 rats by a single intravenous (i.v.) injection of (4.3, 43, 148.5, and 430 mg/kg), or a 6-hr nose-only inhalation exposure (400 ppm) to 14C-2,4-PD. For the i.v. route, the plasma concentration of 14C-2,4-PD-derived radioactivity declined in a biexponential fashion. The overall form of the 14C plasma concentration-time curves and derived pharmacokinetic parameters indicated that dose-linear kinetics occurred in the i.v. dose range 4.3-148.5 mg/kg, but not with 430 mg/kg. Metabolism of 2,4-PD was rapid to undetectable after 8 hr. 14C-2,4-PD derived radioactivity was eliminated mainly as 14CO2 and in urine. For the 4.3, 43 and 148.5 mg/kg doses 14CO2 elimination was relatively constant (36.8, 38.8 and 42.3% in 48 hr samples respectively) and greater than urinary excretion (17.9, 14.3 and 29.6%; 48 hr specimens). At 430 mg/kg i.v. there was a reversal of the excretion pattern, with urine 14C excretion (54.7%) becoming greater than that for 14CO2 (27.3%). Excretion in expired volatiles and feces was small. Radiochromatograms of urine showed free 2,4-PD in the 12 hr sample, together with 7 other metabolites. Free 2,4-PD and 6 of the metabolites decreased or were not detectable in a 24 or 48 hr urine sample, but one peak (retention 7.9 min) increased progressively to become the major fraction (97%). Nose-only exposure to 400 ppm 14C-2, 4-PD produced a mean decrease in breathing rate of 20.1%, which was constant and sustained throughout exposure, due to a lengthening of the expiratory phase of the respiratory cycle. 14C-2,4-PD was rapidly absorbed during the first 3 hr of exposure, then began to plateau, but did not reach a steady state. Postexposure elimination of 14C from plasma followed a biexponential form with a t1/2 for the terminal disposition phase of 30.72 hr. ... Postexposure, plasma unmetabolized 2,4-PD declined rapidly to undetectable concentrations by 12 hr. Radiolabel excretion was approximately equivalent in urine (37.6%) and expired 14CO2 (36.3%). Urine radiochromatograms showed a minor 2,4-PD contaminant (0.6-5.9% over 48 hr), along with 7 other peaks probably representing metabolites. The major metabolite peak was at 7.8 min retention, increasing from 41.1% (12 hr) to 62.8% (48 hr). Immediately postexposure, radioactivity was present in all tissues examined, but on a concentration basis (microgram equiv/g) there was no preferential accumulation of 14C in any tissue or organ.[Frantz SW et al; Toxicol Ind health 14 (3): 413-28 (1998)] **PEER REVIEWED** PubMed Abstract

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Metabolism/Metabolites

  • None found

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Tsca Test Submissions

  • 2,4-Pentanedione was evaluated for the ability to increase the incidence of micronucleated polychromatic erythrocytes in bone marrow of male and female Swiss-Webster mice treated by single i.p. injection (Micronucleus Test). Groups of at least 10 mice (at least 5 males and 5 females) were injected with 2,4-pentanedione in water vehicle at doses of 0, 200, 400 or 650 mg/kg (high-dose = approximately 89% of the LD50). The peripheral blood was sampled for micronucleus evaluation 30, 48, and 72 hrs after dosing. The ratio of normochromatic to polychromatic erythrocytes was not significantly different (p > 0.05, Fisher's Exact Test) in the treated groups compared with the vehicle controls. Statistically significant increases in the numbers of micronuclei were observed at the 30-hr sampling time for male and female mice at the mid- and high-dose levels (p < or = 0.001) and at the 48-hr sampling for the combined sexes at all treatment levels (low-dose level, p < 0.05, and mid- and high-dose, p < or = 0.001).[Bushy Run Research Center, Union Carbide Corp.; 2,4-Pentanedione, In Vivo Mouse Micronucleus Study. (1986), EPA Document No. 89-870000070, Fiche No. OTS0510542-1] **UNREVIEWED**
  • Teratogenicity was evaluated in pregnant female Fischer 344 rats (25/group) exposed by inhalation to 2,4-pentanedione at concentrations of 0, 52.7, 202 or 398 ppm for 6 hrs/day on gestation days (GD) 6-15. Dams were sacrificed on GD 21. Significant differences were observed between treated and control animals in the following: decreased body weights and weight gain (high-dose group on GD 9, 10, 15, and 18), increased relative and absolute liver weights (mid-dose group), decreased fetal body weight/litter (all fetuses at high-dose level, all fetuses and females at mid-dose level), increased incidence of partial fetal atelectasis including unossified cervical centrum, anterior arch of the atlas, and proximal phalanges of the hindlimb, and increased incidence of poorly ossified cervical centrum, thoracic centrum, premaxillary bone of the face, proximal phalanges of the forelimb, metatarsals of the hindlimb, and xiphoid process (high-dose group). No significant differences were observed between treated and control animals in the following: maternal mortality, early deliveries, abortions, clinical observations, thymus, histologic examination of maternal brains, number of corpora lutea, total nonviable or viable implantations/litter, percent pre- or postimplantation loss, live fetuses/litter, fetal sex ratio, and incidence of individual malformations or total external and visceral including craniofacial, and skeletal malformations.[Bushy Run Research Center, Union Carbide Corp.; Evaluation of the Teratogenicity of Inhaled 2,4-Pentanedione in Fischer 344 Rats. (1986), EPA Document No. 89-8600013, Fiche No. OTS0510542] **UNREVIEWED**
  • The ability of 2,4-pentanedione (PD) to cause aberrations in Chinese hamster ovary (CHO) cells in vitro was evaluated in the presence and absence of Aroclor-induced rat liver S9 metabolic activation. Based on preliminary toxicity tests, nonactivated cultures were treated with 0, 0.015, 0.02, 0.025 or 0.03 mg PD/ml producing a cloning efficiency of approximately 76% to 66%. Activated cultures were treated with 0, 0.045, 0.07 or 0.1 mg PD/ml producing a cloning efficiency of approximately 100% to 88%. Cultures were sampled at 6 hrs and 10 hrs and a total of 100 cells were scored/dose level/sampling time. Nonactivated cultures treated with 0.025 mg/ml (10-hr sampling time only) exhibited significant increases (0.05 > p > 0.01, Fisher's Exact Test) in the frequency of cells with chromosomal aberrations relative to the negative controls (water vehicle). Aberrations included chromatid breaks and gaps and chromosome fragments, minute, and gaps. Activated cultures treated with 0.045 mg/ml (6-hr sampling time only) exhibited significant increases (0.05 > p > 0.01, Fisher's Exact Test) in the frequency of cells with chromosomal aberrations relative to the negative controls (water vehicle). Aberrations included chromatid breaks, minutes and gaps and chromosome fragments. No dose-response was observed either with or without metabolic activation.[Bushy Run Research Center, Union Carbide Corp.; 2,4-Pentanedione: In Vitro Cytogenic Testing with Chinese Hamster Ovary Cells. (1986), EPA Document No. FYI-OTS-0286-0434, Fiche No. OTS0000434-0] **UNREVIEWED**
  • The ability of 2,4-pentanedione (PD) to cause aberrations in Chinese hamster ovary (CHO) cells in vitro was evaluated in the presence and absence of Aroclor-induced rat liver S9 metabolic activation. Based on preliminary toxicity tests, nonactivated cultures were treated with 0, 0.08, 0.10 or 0.12 mg PD/ml for 6 hrs and sampled 22 hrs after the initiation of treatment. Activated cultures were treated with 0, 0.10, 0.12 or 0.14 mg PD/ml for 2 hrs and sampled 14 hrs after the initiation of treatment. Selection of test concentrations was based on a 40-60% reduction in the mitotic index. Nonactivated cultures at all treatment levels produced highly statistically significant increases in the frequency of chromosome aberrations relative to (water vehicle) controls (p < 0.001, Fisher's Exact Test). The aberrations included mainly chromatid-type aberrations (breaks, minute fragments and complex rearrangements) and chromosome-type aberrations (minute fragments and severely damaged cells). Smaller numbers of chromatid rings, quadraradials, triradials, and gaps, and chromosome rings and pulverized chromosomes were observed. None of the activated cultures produced statistically significant increases in the frequency of chromosome aberrations relative to controls (p > 0.05).[Bushy Run Research Center, Union Carbide Corp.; 2,4-Pentanedione: In Vitro Chromosome Aberration Study with Chinese Hamster Ovary Cells (Confirmatory Test). (1986), EPA Document No. 89-8600013, Fiche No. OTS0510542] **UNREVIEWED**
  • The ability of 2,4-pentanedione (PD) to induce Sister Chromatid Exchange (SCE) in Chinese hamster ovary (CHO) cells was evaluated both in the presence and absence of Aroclor-induced rat liver S9 metabolic activation. Based on preliminary toxicity tests, PD, diluted with water, was tested at concentrations of 0, 0.02, 0.03 or 0.1 mg/ml without activation and at concentrations of 0, 0.03, 0.1 or 0.3 mg/ml with activation. Nonactivated and activated cultures were exposed to PD for 5 and 2 hrs, respectively. All of the concentrations tested induced a statistically significant increases in the frequencies of SCE relative to controls, both with or without metabolic activation (p < 0.05; Student's t-test, highest concentration with or without activation, p < 0.001).[Bushy Run Research Center, Union Carbide Corp.; 2,4-Pentanedione In Vitro Genotoxicity Studies CHO/HGPRT Gene Mutation Test Sister Chromatid Exchange Assay. (1986), EPA Document No. FYI-OTS-0286-0434, Fiche No. OTS0000434-0] **UNREVIEWED**
  • The ability of 2,4-pentanedione to induce specific locus mutations at the HGPRT locus in cultured Chinese hamster ovary (CHO) cells was evaluated in the presence and absence of Aroclor-induced rat liver S9 metabolic activation. Based on preliminary toxicity tests, nonactivated cultures were treated in duplicate with 0.005, 0.01, 0.05, 0.10, 0.5, 1.0 and 1.5mg/ml, producing a range of 99.5 - 0% survival. Activated cultures treated in duplicate with 0.005, 0.01, 0.05, 0.1, 0.5 and 1.0mg/ml produced a range of 99.8 - 29.2% survival. None of the cultures produced mutant frequencies significantly greater than the solvent control (deionized water).[Bushy Run Research Center; 2,4-Pentanedione; CHO/HGPRT Gene Mutation Test, (1986), EPA Document No. FYI-OTS-0286-0434, Fiche No. OTS0000434-0] **UNREVIEWED**
  • The mutagenicity of 2,4-pentanedione was evaluated in Salmonella tester strains TA98, TA100, TA1535, TA1537 and TA1538 (Ames Test), both in the presence and absence of added metabolic activation by Aroclor-induced rat liver S9 fraction. Based on preliminary toxicity determinations, 2,4-pentanedione, diluted with deionized water, was tested at concentrations up to 30mg/plate using the plate incorporation technique. 2,4-Pentanedione did not cause a positive response in any tester strain with or without metabolic activation.[Bushy Run Research Center; 2,4-Pentanedione: Salmonella/Microsome (Ames) Bacterial Mutagenicity Assay), (1985), EPA Document No. FYI-OTS-0286-0434, Fiche No. OTS0000434-0] **UNREVIEWED**

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Footnotes

1 Source: the NTP's CEBS database.

2 Source: the National Library of Medicine's Hazardous Substance Database, 02/28/2017.

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