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EC number: 201-873-2 | CAS number: 88-99-3
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Link to relevant study record(s)
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: No OECD guideline or GLP defined. No purity of test substance defined.
- Objective of study:
- other: absorbtion, excretion
- Principles of method if other than guideline:
- The toxicokinetic profiles of phthalic acid (PA), were studied in rats after orally administering doses 20, 100, or 500 mg/kg.
- GLP compliance:
- not specified
- Radiolabelling:
- not specified
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Duration and frequency of treatment / exposure:
- single administration of test substance
- Remarks:
- Doses / Concentrations:
20, 100, or 500 mg/kg bw by gavage in corn oil. - No. of animals per sex per dose / concentration:
- 3
- Control animals:
- not specified
- Preliminary studies:
- no data
- Details on absorption:
- The test substance was absorbed rapidly after an oral dose of 500 mg/kg bw with peak concentration (Cmax) in blood (3.5+/- 0.33 µg/ml) at 30 min postadministration.
- Details on distribution in tissues:
- Apparent distribution volumes pf the test substance in the steady state (Vz/F) at 20, 100, or 500 mg/kg bw were 903.28+/- 125.28, 1419.87+/-527.53, and 5264.86+/- 993.65 ml, respectively.
- Transfer type:
- other: no data
- Observation:
- other: no data
- Details on excretion:
- The main route of elimination following a single p.o. dose of test substance was in urine. After administering oral doses of 20,100, or 500 mg/kg bw, the test substance was excreted in urine within 24h. A larger percentage (13-26%) of test substance was excreted in urine following a single oral administration of PA (20-500 mg/kg bw). The results show that PA plasma levels in rats declined in a biphasic fashion after oral administration. The apparent distribution volume in the steady state indicates that PA is distributed extensively into tissues. The total systemic clearance of PA was moderate and significantly less than hepatic blood flow (approximately 3.91 h/kg). PA was absorbed rapidly after oral administration, and peak plasma concentrations were attained 30 min after administration. Urine analysis after the oral administration at 500 mg/kg indicated that only about 13% of unchanged PA is excreted in urine. In conclusion, the present investigation demonstrates that PA concentrations in rat plasma declined following oral administration with a mean terminal elimination half-life of about 5-6h.
- Toxicokinetic parameters:
- half-life 1st: 5-6 h [20 mg/kg]
- Toxicokinetic parameters:
- Tmax: 0.83 +/- 0.29 (h) [20 mg/kg]
- Toxicokinetic parameters:
- Cmax: 4.92 +/- 0.78 (µg/ml) [20 mg/kg]
- Toxicokinetic parameters:
- AUC: (µg-h/ml) 44.69 +/- 2.56 [20 mg/kg]
- Toxicokinetic parameters:
- half-life 1st: 5.19 +/- 3.56 (h) [100 mg/kg]
- Toxicokinetic parameters:
- Tmax: 1.00 +/- 0.87 (h) [100 mg/kg]
- Toxicokinetic parameters:
- Cmax: 15.87 +/- 1.68 (µg/ml) [100 mg/kg]
- Toxicokinetic parameters:
- AUC: (µg-h/ml) 107.64 +/- 31.77 [100 mg/kg]
- Toxicokinetic parameters:
- half-life 1st: 5.10 +/- 1.19 (h) [500 mg/kg]
- Toxicokinetic parameters:
- Tmax: 0.67 +/- 0.29 (h) [500 mg/kg]
- Toxicokinetic parameters:
- Cmax: 20.49 +/- 3.64 (µg/ml) [500 mg/kg]
- Toxicokinetic parameters:
- AUC: (µg-h/ml) 146.90 +/- 9.33) [500 mg/kg]
- Metabolites identified:
- not specified
- Details on metabolites:
- no data
- Executive summary:
The toxicokinetic profiles of phthalic acid (PA), were studied in rats after orally administering doses 20, 100, or 500 mg/kg. Concentrations of PA were determined in serum or urine by high-performance liquid chromatography (HPLC). The plasma concentrations of PA showed a biexponential increase following oral administration of doses ranging from 20 to 500 mg/kg. The terminal elimination half-lives (t1/2) of PA at dosages of 20, 100, or 500 mg/kg were 6.46+ 1.13, 5.19 +3.56, and 5.10 +1.10 h respectively, total clearances (CL/F) of PA at 20, 100, or 500 mg/kg were 97.43 +4.20, 215.01 +55.42, and 721.07 +51.81 ml/h, and apparent distribution volumes of PA in the steady state (Vz/F) at 20, 100, or 500 mg/kg were 903.28 +125.28, 1419.87 +527.53, and 5264.86 +993.65 ml, respectively. PA was absorbed rapidly after an oral dose of 500 mg/kg with peak concentration (Cmax) in blood (3.5 +0.33 µg/ml) at 30 min post administration. After oral administration, the dose-normalized area under the curve (AUC) (146.90 +9.33 µg/h/ml) for 500 mg/kg was significantly greater than at 20 mg/kg ( 44.69 +2.56 µg/h/ml). Urine analysis indicated that 13 +0.45% of the administered PA dose (at 500 mg/kg, p.o.) was recovered unchanged in urine within 24 h.
Reference
Toxicokinetic Parameters in Plasma Determined by Noncompartmental Analysis of the Time Course of Phthalic Acid (PA) Following the Oral Administration of 20, 100, or 500 mg/kg PA as a Single Dose.
Parameters | Mean +SD |
20mg/kg | |
Tmax (h) | 0.83 +0.29 |
Cmax (µg/ml) | 4.92 +0.78 |
Ke (1/h) | 0.11 +0.02 |
t1/2 (h) | 5.46 +1.13 |
AUC (µg-h/ml) | 44.69 +2.56 |
Vz/F (ml) | 903.28 +125.28 |
CL/F (ml/h) | 97.43 +4.20 |
AUMC (µg-h²/ml) | 438.92 +74.15 |
MRT (h) | 9.79 +1.21 |
100 mg/kg | |
Tmax (h) | 1.00 +0.87 |
Cmax (µg/ml) | 15.87 +1.68 |
Ke (1/h) | 0.17 +0.09 |
t1/2(h) | 5.19 +3.56 |
AUC (µg-h/ml) | 107.64 +31.77 |
Vz/F (ml) | 1419.87 +527.53 |
CL/F (ml/h) | 215.01 +55.42 |
AUMC (µg-h²/ml) | 1003.41 +747.31 |
MRT (h) | 8.58 +3.83 |
500 mg/kg | |
Tmax (h) | 0.67 +0.29 |
Cmax (µg/ml) | 20.49 +3.64 |
Ke (1/h) | 0.14 +0.03 |
t1/2(h) | 5.10 +1.19 |
AUC (µg-h/ml) | 146.90 +9.33 |
Vz/F (ml) | 5264.86 +993.65 |
CL/F (ml/h) | 721.07 +51.81 |
AUMC (µg-h²/ml) | 1344.52 +325.99 |
MRT (h) | 9.09 +1.63 |
Tmax- time to reach peak plasma concentration,
Cmax-maximum plasma concentration,
Ke- Rate constant associated with the terminal phase,
t1/2- elimination half-life in plasma,
AUC- area under the concentration-time curve,
Vz/F- apparent distribution volume,
CL/F- total body clearance,
MRT- mean residence time.
Concentration of Phthalic Acid (PA) in Urine Samples After Its Oral Administration to Male Rats:
Time interval (h) | Conc. (µg/ml) | Urine Volume (ml) | PA #1 (total amount excreted, µg) | Conc. (µg/ml) | Urine Volume (ml) | PA #2 (total amount excreted, µg) | Conc.(µg/ml) | Urine Volume (ml) | PA #3 (total amount excreted, µg) |
PA-500 mg/kg | |||||||||
0 -4 | 12492.67 | 1.0 | 12492.67 | 5814.89 | 2.0 | 11629.77 | 7306.40 | 2.0 | 14612.79 |
4 -8 | 9410 .84 | 2.4 | 22586.01 | 12149.83 | 2.0 | 24299.65 | 11642.85 | 1.8 | 20957.13 |
8 -12 | 6386.03 | 2.4 | 15326.47 | 5611.77 | 2.5 | 14029.43 | 5648.68 | 1.8 | 10167.62 |
12 -16 | 3713.82 | 1.8 | 6684.87 | 5319.60 | 2.0 | 10639.20 | 4379.18 | 1.8 | 7882.52 |
16 -24 | 3311.50 | 2.0 | 6622.99 | 1228.05 | 4.0 | 4912.18 | 1047.12 | 4.0 | 4188.48 |
PA-100 mg/kg | |||||||||
0 -4 | 4154.18 | 2.0 | 8308.35 | 5629.77 | 1.0 | 5629.77 | 4869.44 | 2.0 | 9738.87 |
4 -8 | 6369.44 | 2.0 | 12738.87 | 5639.02 | 2.5 | 14097.55 | 5425.86 | 2.5 | 13564.64 |
8 -12 | 1441.43 | 2.0 | 2882.86 | 2122.93 | 2.5 | 5307.33 | 1880.74 | 3.0 | 5642.21 |
12 -16 | 549.18 | 3.0 | 1647.54 | 1402.85 | 2.0 | 2805.70 | 681.56 | 2.5 | 1703.90 |
16 -24 | 170 .06 | 3.0 | 510.17 | 529.60 | 2.0 | 1059.19 | 248.59 | 4.5 | 1118.64 |
PA-20 mg/kg | |||||||||
0 -4 | 558.15 | 2.0 | 1116.3 | 503.30 | 2.0 | 1006.59 | 443.29 | 2.0 | 886.58 |
4 -8 | 375.97 | 2.5 | 939.92 | 313.06 | 2.5 | 782.65 | 380.94 | 2.0 | 761.87 |
8 -12 | 248.87 | 2.0 | 497.74 | 119.10 | 4.0 | 476.39 | 172.43 | 2.5 | 431.07 |
12 -16 | 138.78 | 2.5 | 346.94 | 158.34 | 2.0 | 316.68 | 70.28 | 4.0 | 281.10 |
16 -24 | 81.80 | 3.0 | 245.39 | 29.17 | 8.0 | 233.37 | 133.37 | 2.0 | 266.73 |
Description of key information
Phthalic acid administered orally to the rat is rapidly absorbed by the gastrointestinal tract with peak plasma concentrations after 30 minutes and a short terminal half-life of 5-6 h. PA is not retained in the organs or tissues and is almost quantitatively excreted in feces and urine as unchanged PA. The main excretion route was the feces followed by urine.
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
Additional information
The toxicokinetic profiles of phthalic acid (PA), were studied in rats after orally administering doses 20, 100, or 500 mg/kg. Concentrations of PA were determined in serum or urine by high-performance liquid chromatography (HPLC). The plasma concentrations of PA showed a biexponential increase following oral administration of doses ranging from 20 to 500 mg/kg. The terminal elimination half-lives (t1/2) of PA at dosages of 20, 100, or 500 mg/kg were 6.46+1.13, 5.19+3.56, and 5.10+1.10 h respectively, total clearances (CL/F) of PA at 20, 100, or 500 mg/kg were 97.43+4.20, 215.01+55.42, and 721.07+51.81 ml/h, and apparent distribution volumes of PA in the steady state (Vz/F) at 20, 100, or 500 mg/kg were 903.28+125.28, 1419.87+527.53, and 5264.86+993.65 ml, respectively. PA was absorbed rapidly after an oral dose of 500 mg/kg with peak concentration (Cmax) in blood (3.5+0.33 µg/ml) at 30 min post administration. After oral administration, the dose-normalized area under the curve (AUC) (146.90+9.33 µg/h/ml) for 500 mg/kg was significantly greater than at 20 mg/kg (44.69+2.56 µg/h/ml). Urine analysis indicated that 13+0.45% of the administered PA dose (at 500 mg/kg, p. o.) was recovered unchanged in urine within 24 h (Lim, 2007).
In a toxicokinetic study following a single oral dose of carbonyl labeled phthalic acid to rats 95% of the radioactivity was recovered as phthalic acid in the feces and urine. The distribution between the feces and the urine was relatively independent of the dose level with 70-80% of the radioactivity in the feces and 20 -25% in the urine. No metabolites of phthalic acid could be detected in the feces or the urine but a small amount of the phthalic acid was converted to carbon dioxide (0.11 – 0.15%). Four hours after dosing approximately 2% of the radioactivity was distributed throughout the organs and tissues with most of this radioactivity detected in the liver, kidney, spleen and testes. No radioactivity could be detected in these organs twenty-four hours after dosing. (Williams, 1974).
These results indicate that phthalic acid administered orally to the rat is rapidly absorbed by the gastrointestinal tract with peak plasma concentrations after 30 minutes and a short terminal half-life of 5-6 h. PA is not retained in the organs or tissues and is almost quantitatively excreted in feces and urine as unchanged PA. The main excretion route was the feces followed by urine.
No experimental data on PA is available for some toxicological endpoints. For these endpoints read across with phthalic anhydride is proposed due to the rapid hydrolysis of phthalic anhydride to the phthalic acid. In an in vitro hydrolysis test the rate of hydrolysis of phthalic anhydride was determined at different pHs at 25°C in water/buffer containing a small amount of acetonitrile. Phthalic anhydride hydrolyses rapidly in the presence of water forming phthalic acid. Half-life for phthalic anhydride was 30.5 seconds at pH 7.24. At pH 6.8 the half-life of phthalic anhydride in water was prolonged to 61 seconds (Andrés, 2001).
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