Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 442-450-4 | CAS number: -
- 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
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 05 Dec 2007 - 28 Jul 2008
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 008
- Report date:
- 2008
Materials and methods
- Objective of study:
- absorption
- distribution
- excretion
- mass balance
- metabolism
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 417 (Toxicokinetics)
- Version / remarks:
- adopted in 1984
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 417 (Toxicokinetics)
- Version / remarks:
- adopted in 2010
- Deviations:
- yes
- Remarks:
- age of the animals not reported
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Swiss Federal Office of Public Health, Consumer protection directorate, Notification authority for chemicals, Bern, Switzerland
Test material
- Reference substance name:
- -
- EC Number:
- 442-450-4
- EC Name:
- -
- Cas Number:
- 203255-81-6
- Molecular formula:
- C42H61O4P
- IUPAC Name:
- 6-(3-(3-tert-Butyl-4-hydroxy-5-methylphenyl)propoxy)-2,4,8,1 0-tetra-tert-butyldibenz(d,f)(1,3,2)dioxaphosphepin
Constituent 1
- Radiolabelling:
- yes
Test animals
- Species:
- rat
- Strain:
- other: CD (SD) IGS
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River, Kissleg, Germany
- Weight at study initiation: 238 ± 21 g (males) and 217 ± 21 g (femlaes)
- Housing: In groups of 1-3/sex under conventional hygienic conditions in Makrolon cages with standard soft wood bedding during acclimation. Individually in metabolism cages during the course of the study.
- Diet: Pelleted 3433 Kliba rat maintenance diet (Provimi Kliba AG, Kaiseraugstm Switzerland), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: at least 5 days
- Health status: The health status of the treated animals was checked visually at daily intervals
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: aqueous methyl cellulose
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
Stock solutions of 14C-labeled test items were prepared by mixing aliquot amounts of unlabeled test item with 14C-labeled test item (MOH or TBPH-label) in 10 mL of hexane (10 mg/kg bw, groups 3, 4, 7, and 8) or dichloromethane (1000 mg/kg bw, groups 5 and 6) in a volumetric flask.
MOH-labelled test item, 10 mg/kg bw: (groups 3+4)
9.95 mL of the stock solution were transferred into a volumetric flask and the solvent was evaporated under a nitrogen stream. The test item was pre-dissolved in 1.5 mL of DMSO and 0.5% methocel solution was added to a total volume of 30 mL under stirring. Test item concentration and homogeneity was verified by LSC measurements of triplicate samples. The resulting test item concentration in the application solution was 0.98 mg/g.
TBPH-labelled test item, 10 mg/kg bw: (groups 7+8)
9.85 mL of the stock solution were transferred into a volumetric flask and the solvent was evaporated under a nitrogen stream. The test item was pre-dissolved in 1.5 mL of DMSO and 0.5% methocel solution was added to a total volume of 30 mL under stirring. Test item concentration and homogeneity was verified by LSC measurements of triplicate samples. The resulting test item concentration in the application solution was 0.98 mg/g
TBPH-labelled test item, 1000 mg/kg bw: (groups 5+6)
The complete stock solution was transferred into a 100 mL round bottom flask and 30 mL 0.5% methocel solution were added. The dichloromethane solvent was evaporated in a nitrogen stream under vigorous stirring and further 10-12 mL methocel solution added to replace loss by evaporation and to reach a suitable consistency for administration. The concentration of the test item solution was determined by LSC to be 67.8 mg/g. The formulation was kept under permanent stirring until administration. - Duration and frequency of treatment / exposure:
- single administration
Doses / concentrationsopen allclose all
- Dose / conc.:
- 10 mg/kg bw/day (nominal)
- Remarks:
- equivalent to 9.80 ± 0.18 mg/kg bw in males and 9.98 ± 0.30 mg/kg bw in females;
low dose MOH-label, groups 3 (males) and 4 (females), corresponding to 25 MBq (0.67 mCi)
- Dose / conc.:
- 10 mg/kg bw/day (nominal)
- Remarks:
- equivalent to 9.65 ± 0.19 mg/kg bw in males and 10.10 ± 0.30 mg/kg bw in females;low dose TBPH-label, groups 7 (males) and 8 (females), corresponding to 25 MBq (0.67 mCi)
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- Remarks:
- equivalent to 992 ± 45 mg/kg bw in males and 991 ± 73 mg/kg bw in females;
high dose TBPH-label, groups 5 (males) and 6 (females), corresponding to 50 MBq (1.35 mCi)
- No. of animals per sex per dose / concentration:
- 4
- Control animals:
- no
- Details on study design:
- - Dose selection rationale: Comparison of the excretion balance after administration of 2 labels (MOH and TBPH) and between a high dose (1000 mg/kg bw) and a low dose (10 mg/kg bw).
- Details on dosing and sampling:
- TOXICOKINETIC / PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, faeces, cage washes, blood, carcass and tissues. As tissues, the adrenal glands, blood, brain, epididymes , eyes , fat, femur, heart, kidney, large intestinal tract, liver, lung , muscle , ovaries, pancreas , pituitary gland, plasma , prostate gland , sciatic nerve, skin (back region), small intestinal tract, spinal cord, spleen, stomach, testes , thymus, thyroid gland, urinary bladder and uterus were collected. Additionally, the contents of the stomach, large intestine and small intestine of each animal were pooled and analysed.
- Time and frequency of sampling:
urine: 0-8, 8-24, 24-48, 48-72, 72-96, 96-120, 120-144, and 144-168 h after administration
faeces: 0-24, 24-48, 48-72, 72-96, 96-120, 120-144, and 144-168 h after administration
blood: at sacrifice after 168 h
organs/tissues/carcass: at sacrifice after 168 h
cage wash: 0-8 and 0-24 h after administration
SAMPLE PROCESSING
CAGE WASH: At the end of the each interval 0-8 and 0-24 h collection intervals, the metabolism cages were rinsed with a small amount of purified water (about 5-10 mL) to remove any remaining droplets of urine. The rinsings were added to the initially sampled urine and the radioactivity was evaluated. At the end of the study, the cages were washed with ethanol, water/acetone (50/50, v/v) and/or appropriate solvnts for the determination of any residual radioactivity.
URINE: Subsamples of urine were mixed at room temperature with liquid scintillation counting (LSC) cocktail (IRGA-SAFE PLUSTM, Perkin Elmer) analysed by LSC. Counting was performed using a Packard TRI-CARBTM Liquid Scintillation Analyser (model 2500 TR).
FAECES: Faeces samples were homogenised wet by addition of water (about 1+2, w/v). After homogenization, the radioactivity was determined from appropriate aliquots after solubilisation with tissue solubiliser (Solvable, Perkin Elmer).
CARCASS: The carcass was homogenized and the radioactivity was determined from appropriate aliquots of the homogenate after solubilisation with tissue solubiliser (Solvable, Perkin Elmer).
ORGANS / BLOOD: Subsamples were digested with tissue solubiliser (Solvable, Perkin Elmer), followed by determination of radioactivity.
INTESTINAL TRACT: The contents of the stomach, large intestine and small intestine of each animal were pooled, homogenised wet by addition of water (about 1+2, w/v and radioactivity was determined from appropriate aliquots after solubilisation with tissue solubiliser (Solvable, Perkin Elmer).
PLASMA: Plasma samples were directly measured for radioactivity.
BONE: The femur was combusted and radioactivity was determined thereafter.
EXTRACTION OF FAECES POOLS
Faeces samples of the 24 and 48 h collection time points were pooled per group and extracted 3 times with neural acetonitrile, followed by a further extraction with 0.1 M HCl/Acetonitrile (2:8). The 0-24 h faeces pools of the group 3 animals were extracted with ethyl acetate before the acidic acetonitrile extraction. As this additional step did not improve the recovery, all other pools were processed without ethyl acetate extraction. The extracts were combined, concentrated and analysed by HPLC.
PURIFICATION OF URINE POOLS
Four pools were generated of the individual urine samples of the group 3 and 4 animals, collection intervals 0-8 and 8-24 h with 2 mL urine per animal and collection interval. A Separtis Isolute RP18 solid phase extraction column1 (5 g sorbent mass) was pre-conditioned with 0.1% aqueous ammonium acetate. 8 mL of urine per group were transferred onto the column and eluted with 0.1% aqueous ammonium acetate (approximately 11 mL per pool) and 100% methanol (4.1 - 4.4 mL). Total activity in all fractions was determined, the total recovery was 88- 102%. The methanol fractions were analysed by HPLC.
METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled: urine and faeces
- Time and frequency of sampling:
urine: 0-8, 8-24 and 24-48 h after administration
faeces: 0-24 and 24-48 h after administration
- From how many animals: sampled were pooled for each sex and dose group
- Method types for identification: HPLC with UV detector and radiodetector, Liquid scintillation counting (LSC)
- Limits of detection and quantification: Limits of detection (LOD) and limits of quantification (LOQ) for liquid scintillation counting were calculated according to L.A. Currie (Anal. Chem. 40, 586 (1968)) from the specific radioactivity of the test item.
ANALYTICAL METHODS :
Measurement of radioactivity
Radioactivity in all specimens was determined on Packard liquid scintillation counters (e.g. TRICARB 2500 TR, 2550 TR/LL or 2900 TR) using the Transformed Spectral Index of the External Standard Spectrum (tSIE) method for quench correction. All measurements were performed as far as possible at least in duplicate for a counting time allowing a counting error below 1% or for a maximal counting time of 10 minutes. All measurements were performed with scintillation background correction. In case duplicates differed by more than 10% from the mean value, as far as possible re-analyses were performed using fresh aliquots (except for measurements below 100 dpm).
The following scintillation mixtures were used:
A: Irga-Safe Plus (Perkin Elmer)
B: Solvable (Perkin Elmer)
Water: Milli-Q water (Milli-Q plus 185, Millipore)
HPLC analysis
HPLC analysis was used for the determination of the purity of the administration solutions and for the determination of metabolites in urine and feces. The retention time of parent compound was determined for comparison with chromatograms of faeces samples. Analyses were performed with a HPLC-system consisting of a gradient pump (Merck-Hitachi L-6200), an autosampler (Merck-Hitachi AS-2000 A), an UV-detector (Merck-Hitachi L-4000), a radiodetector and a data processing system (Packard FLOW-ONE, Beta A 500).
For details on the methods used, please refer to Table 1 under "Any other information on materials and methods incl. tables". - Statistics:
- The concentration of radioactivity in blood and plasma were expressed as parent equivalents on a fresh weight basis (pg eq/mL or g), and compared with the limits of quantification. Limits of detection (LOD) and limits of quantification (LOQ) for liquid scintillation counting were calculated according to L.A. Currie (Anal. Chem. 40, 586 (1968)) from the specific radioactivity of the test item.
Results and discussion
Main ADME resultsopen allclose all
- Type:
- absorption
- Results:
- Both the MOH and the TBPH label were completely recovered in excreta, organs, tissues and carcass and in the cage wash. The mass balance in all groups ranged between 91.7-101%.
- Type:
- distribution
- Results:
- Residues in the tissues at sacrifice were generally low. With the MOH label, the highest concentrations were found in the liver & kidney. Residues of the TBPH label were primarily found in adrenal glands, thyroid gland, liver, fatty tissue & ovaries.
- Type:
- excretion
- Results:
- Both labels of the test item were rapidly excreted. 91-100% of the applied dose was recovered in urine and faeces within the first 48 h after administration. The major route of excretion was via the faeces.
- Type:
- metabolism
- Results:
- 15 metabolites detected in faeces (5 attr to unchanged parent/references, 10 unknown). 10 mg/kg bw (MOH/TBPH): the major metabolite was attr to ref.compound NP-2018 (45-71%). 1000 mg/kg bw: the major metabolite was attr to unchanged parent (62-65%).
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- The mass balance in all test groups ranged from 91.7 - 101% (refer to Table 2 under "Any other information on results incl. tables"). As the main excretion route was via the faeces (>90% of the dose for all test groups), the extent of oral absorption could not be determined.
- Details on distribution in tissues:
- In males and females of both labels and in all dose groups, the major part of the administered dose was excreted via the faeces. At the time of sacrifice, 0.065 - 0.27% (males) and 0.03 – 0.195% (females) of the dose were found in the organs, tissues, carcass and the content of the gastrointestinal tract. After administration of 10 mg/kg bw MOH-labelled test item, the highest concentrations found were in the kidneys and in the liver.
After administration of 10 or 1000 mg/kg bw TBPH-labelled test item, the highest amounts were found in the adrenal glands, liver, thyroids, ovaries and in fat. There were no marked differences found between males and females and between the low and the high dose group. For details, please refer to Table 3 under "Any other information on results incl. tables".
- Details on excretion:
- For both labels and both dose groups, the major excretion route was via the faeces (90.5 - 101% of the dose). There was no difference between males and females. Urinary excretion accounted for 1.14 – 1.77% of the dose for the MOH label and 0.05% or less for the TBPH label. More than 90% of the dose was excreted within 48 h post dosing. For details, please refer to Table 2 under "Any other information on results incl. tables".
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- Metabolites were identified in the faeces (all treatment groups) and in the urine (MOH-labelled treatment group only).
In the faeces, 87 – 115% of the administered dose were recovered (refer to Table 4 under “Any other information on results incl. tables”). A total of 15 metabolite fractions were identified, 10 of them with unknown origin. Within the low dose groups, about 3.6 – 6.3% (groups 3 and 4 with 10 mg/kg bw MOH-labelled substance) and 17-23% (groups 7 and 8 with 10 mg/kg bw TBPH-labelled substance) of the parent compound were identified in the faeces. The main metabolite in the low dose group of both labels was F4, attributed to reference substance NP-2018.
In the high dose group (groups 5 and 6 with 1000 mg/kg bw TBPH-labelled substance), 62-65% of the radioactivity were attributed to unchanged parent substance and the main metabolite F4 accounted for 12-14% of the dose. The MOH label (groups 3 and 4) formed a more complex metabolite pattern as compared to the TBPH label. The relatively polar fractions F10-F15 were only observed with the MOH label, only F11 (2.4 – 3.6%), attributed to MOH, was more abundant than 1% of the dose. For details, refer to Table 6 under “Any other information on results incl. tables”.
In the urine samples, only the MOH-labelled test item groups (3 and 4) contained sufficient radioactivity for investigation. Recoveries were 88 – 102% (refer to Table 5 under “Any other information on results incl. tables”). Only two polar fractions were identified, with shorter retention times than any of the reference compounds. Parent and reference compounds were not found. For details, refer to Table 7 under “Any other information on results incl. tables”.
Any other information on results incl. tables
Table 2: Mean mass balance after a single oral administration of radiolabelled test material
Label | MOH | TBPH | |||||||||||
Dose group (mg/kg bw) | 10 | 10 | 1000 | ||||||||||
Sex | male | female | male | female | male | female | |||||||
Test group | 3 | 4 | 7 | 8 | 5 | 6 | |||||||
Compartment | Interval (h) | Mean | SD | Mean | SD | Mean | SD | Mean | SD | Mean | SD | Mean | SD |
Urine | 0-8 | 0.432 | 0.136 | 0.327 | 0.116 | 0.002 | 0.000 | 0.001 | 0.000 | 0.015 | 0.008 | 0.001 | 0.000 |
8-24 | 1.060 | 0.250 | 0.650 | 0.248 | 0.005 | 0.002 | 0.045 | 0.086 | 0.006 | 0.005 | 0.002 | 0.002 | |
24-48 | 0.189 | 0.062 | 0.103 | 0.044 | 0.002 | 0.001 | 0.001 | 0.000 | 0.004 | 0.002 | 0.001 | 0.000 | |
48-72 | 0.041 | 0.012 | 0.025 | 0.010 | 0.001 | 0 .000 | <0.001 | - | 0.003 | 0.003 | 0.001 | 0.000 | |
72-96 | 0.021 | 0.004 | 0.013 | 0.004 | <0.001 | - | <0.001 | - | 0.006 | 0.003 | 0.001 | - | |
96-120 | 0.012 | 0.002 | 0.009 | 0.002 | <0.001 | - | <0.001 | - | 0.001 | 0.001 | 0.001 | - | |
120-144 | 0.009 | 0.002 | 0.006 | 0.002 | <0.001 | - | <0.001 | - | 0.003 | 0.003 | 0.001 | - | |
144-168 | 0.007 | 0.001 | 0.005 | 0.001 | <0.001 | - | <0.001 | - | 0.002 | 0.001 | <0.001 | - | |
Subtotal | 1.770 | 0.370 | 1.140 | 0.420 | 0.010 | 0.004 | 0.047 | 0.087 | 0.040 | 0.025 | 0.006 | 0.003 | |
Faeces | 0-24 | 89.2 | 3.3 | 83.1 | 5.2 | 89.2 | 5.9 | 90.5 | 3.6 | 90.6 | 2.0 | 83.2 | 9.7 |
24-48 | 3.16 | 1.67 | 6.89 | 3.30 | 7.10 | 4.39 | 4.71 | 1.74 | 8.89 | 2.10 | 13.50 | 9.20 | |
48-72 | 0.391 | 0.572 | 0.301 | 0.217 | 0.198 | 0.112 | 0.118 | 0.020 | 0.615 | 0.339 | 0.703 | 1.119 | |
72-96 | 0.068 | 0.053 | 0.196 | 0.328 | 0.046 | 0.020 | 0.038 | 0.019 | 0.169 | 0.173 | 0.027 | 0.034 | |
96-120 | 0.033 | 0.008 | 0.013 | 0.008 | 0.024 | 0.008 | 0.929 | 1.814 | 0.148 | 0.102 | 0.016 | - | |
120-144 | 0.021 | 0.007 | 0.006 | 0.002 | 0.018 | 0.006 | 0.018 | 0.005 | 0.086 | 0.062 | 0.008 | - | |
144-168 | 0.016 | 0.004 | 0.005 | 0.001 | 0.014 | 0.005 | 0.016 | 0.004 | 0.080 | 0.050 | 0.012 | - | |
Subtotal | 92.9 | 2.5 | 90.5 | 2.3 | 96.6 | 1.7 | 96.3 | 2.3 | 101.0 | 1.0 | 97.5 | 2.4 | |
Cage wash | 0.013 | 0.005 | 0.018 | 0.012 | 0.002 | 0.001 | 0.008 | 0.014 | 0.062 | 0.044 | 0.002 | 0.000 | |
Total excreted | 94.7 | 2.5 | 91.7 | 2.1 | 96.6 | 1.7 | 96.3 | 2.36 | 101.0 | 1.0 | 97.5 | 2.4 | |
Liver | 0.044 | 0.012 | 0.016 | 0.004 | 0.037 | 0.012 | 0.052 | 0.011 | 0.008 | 0.003 | 0.006 | 0.001 | |
Kidney | 0.014 | 0.005 | 0.010 | 0.003 | 0.002 | 0.001 | 0.002 | 0.001 | <0.005 | - | <0.001 | - | |
Organs/tissues | 0.059 | 0.016 | 0.027 | 0.007 | 0.056 | 0.017 | 0.075 | 0.017 | 0.007 | 0.005 | 0.006 | 0.001 | |
Carcass | 0.031 | 0.007 | 0.016 | 0.002 | 0.097 | 0.026 | 0.114 | 0.020 | 0.252 | 0.253 | 0.047 | 0.055 | |
Intestinal tract contents | 0.006 | 0.002 | 0.002 | 0.000 | 0.006 | 0.002 | 0.006 | 0.001 | 0.009 | 0.007 | 0.002 | 0.001 | |
Subtotal | 0.065 | 0.025 | 0.029 | 0.010 | 0.159 | 0.045 | 0.195 | 0.037 | 0.268 | 0.263 | 0.056 | 0.057 | |
Total | 94.8 | 2.5 | 91.7 | 2.1 | 96.7 | 1.7 | 96.5 | 2.4 | 101.0 | 1.0 | 97.5 | 2.4 |
Table 3: Distribution in tissues [µg eq/g]
Label | MOH | TBPH | ||||||||||
Dose group (mg/kg bw) | 10 | 10 | 1000 | |||||||||
Sex | male | female | male | female | male | female | ||||||
Test group | 3 | 4 | 7 | 8 | 5 | 6 | ||||||
Tissue | Mean | SD | Mean | SD | Mean | SD | Mean | SD | Mean | SD | Mean | SD |
Adrenal Glands | <0.036 | - | <0.036 | - | 0.084 | 0.027 | 0.238 | 0.073 | <3.461 | - | 7.370 | 5.290 |
Blood | 0.008 | - | <0.007 | - | <0.007 | - | 0.008 | - | <0.692 | - | <0.692 | - |
Brain | <0.007 | - | <0.007 | - | <0.007 | - | <0.007 | - | <0.692 | - | <0.692 | - |
Epididymes | <0.007 | - | - | - | 0.013 | 0.004 | - | - | <0.692 | - | - | - |
Eyes | <0.007 | - | - | - | <0.007 | - | <0.007 | - | <0.692 | - | <0.692 | - |
Fat | 0.011 | - | 0.009 | - | 0.031 | 0.006 | 0.033 | 0.009 | 0.867 | 0.059 | 1.580 | 1.140 |
Femur | <0.008 | - | <0.008 | - | 0.008 | - | 0.009 | 0.002 | <0.733 | - | <0.733 | - |
Heart | <0.008 | - | <0.008 | - | 0.013 | 0.003 | 0.019 | 0.007 | <0.733 | - | 1.100 | - |
Kidney | 0.165 | 0.045 | 0.130 | 0.042 | 0.018 | 0.006 | 0.026 | 0.007 | <0.733 | - | 1.590 | - |
Large intestinal tract | <0.008 | - | <0.008 | - | 0.013 | 0.002 | 0.014 | 0.003 | <0.733 | - | <0.733 | - |
Liver | 0.089 | 0.021 | 0.035 | 0.008 | 0.072 | 0.025 | 0.117 | 0.032 | 1.380 | 0.689 | 2.13 | 2.04 |
Lung | <0.008 | - | <0.008 | - | 0.020 | 0.009 | 0.031 | 0.009 | 0.769 | - | 2.000 | - |
Muscle | <0.007 | - | <0.007 | - | 0.008 | 0.001 | 0.011 | 0.002 | <0.692 | - | <0.692 | - |
Ovaries | - | - | 0.007 | - | - | _ | 0.126 | 0.054 | _ | - | 2.980 | 3.440 |
Pancreas | <0.007 | - | <0.007 | - | 0.026 | 0.008 | 0.032 | 0.009 | 0.930 | - | 2.060 | - |
Pituitary gland | <0.072 | - | <0.072 | - | <0.070 | - | <0.070 | - | <6.921 | - | <6.921 | - |
Plasma | <0.007 | - | <0.007 | - | <0.007 | - | 0.008 | - | <0.692 | - | <0.692 | - |
Prostat gland | <0.007 | - | - | - | 0.016 | 0.004 | - | - | <0.692 | - | - | - |
Sciatic nerve | <0.144 | - | <0.144 | - | <0.141 | - | <0.141 | - | <13.843 | - | <13.843 | - |
Skin backregion | <0.007 | - | <0.007 | - | 0.011 | 0.001 | 0.016 | 0.002 | <0.692 | - | 1.030 | - |
Small intestinal tract | 0.011 | 0.002 | 0.008 | 0.000 | 0.023 | 0.006 | 0.024 | 0.008 | <0.692 | - | 1.200 | - |
Spinal cord | <0.007 | - | <0.007 | - | <0.007 | - | <0.007 | - | <0.692 | - | <0.692 | - |
Spleen | <0.008 | - | <0.008 | - | 0.024 | 0.010 | 0.030 | 0.008 | <0.779 | - | 2.120 | - |
Stomach | <0.007 | - | <0.007 | - | 0.014 | 0.005 | 0.018 | 0.004 | <0.692 | - | 1.300 | - |
Testes | <0.007 | - | - | - | 0.010 | 0.002 | - | - | <0.692 | - | - | - |
Thymus | <0.007 | - | <0.007 | - | 0.015 | 0.005 | 0.017 | 0.004 | <0.692 | - | 0.928 | - |
Thyroid gland | 0.030 | 0.008 | 0.030 | 0.004 | 0.038 | 0.013 | 0.045 | 0.017 | 3.640 | 0.880 | 3.430 | 1.160 |
Urinary bladder | <0.072 | - | <0.072 | - | <0.070 | - | <0.070 | - | <6.921 | - | <6.921 | - |
Uterus | - | - | <0.072 | - | - | - | <0.070 | - | - | - | <6.921 | - |
< below lower limit of quantification |
Table 4: Recovery of radioactivity from the faeces
Label | MOH | TBPH | ||||||||||
Dose group (mg/kg bw) | 10 | 10 | 1000 | |||||||||
Sex | male | female | male | female | male | female | ||||||
Test group | 3 | 4 | 7 | 8 | 5 | 6 | ||||||
Tissue | % in faeces | % of dose | % in faeces | % of dose | % in faeces | % of dose | % in faeces | % of dose | % in faeces | % of dose | % in faeces | % of dose |
0-24 h | 92 | 82 | 87 | 73 | 85 | 75 | 88 | 73 | 93 | 83 | 88 | 73 |
24-48 h | 97 | 3 | 115 | 8 | 94 | 5 | 103 | 7 | 94 | 5 | 103 | 7 |
Table 5: Recovery of radioactivity from the urine of rats administered 10 mg/kg bw test item labelled with MOH
Label | MOH | |||
Dose group (mg/kg bw) | 10 | |||
Sex | male | female | ||
Test group | 3 | 4 | ||
Tissue | % in urine | % of dose | % in urine | % of dose |
0-8 h | 88 | 0.38 | 100 | 0.32 |
8-24 h | 92 | 0.98 | 102 | 0.67 |
Table 6: Metabolites identified in the faeces
Label | MOH | TBPH | ||||||
Dose group (mg/kg bw) | 10 | 10 | 1000 | |||||
Sex | male | female | male | female | male | female | ||
Test group | 3 | 4 | 7 | 8 | 5 | 6 | ||
Fraction | Designation | Retention time | 0-48 h | 0-48 h | 0-48 h | 0-48 h | 0-48 h | 0-48 h |
F1 | Parent compound | 23.2-25.0 | 3.6 | 6.3 | 17.0 | 23.3 | 65.3 | 61.6 |
F2 | 20.9-23.3 | 3.6 | 3.9 | 3.1 | 3.1 | <0.05 | 0.4 | |
F3 | 20.1-22.4 | 1.2 | 1.0 | - | - | 0.5 | 0.5 | |
F4 | NP-2018 | 18.8-21.1 | 70.6 | 63.9 | 51.8 | 45.3 | 14.1 | 11.8 |
F5 | 17.5-18.9 | 1.9 | 1.6 | 1.1 | 1.0 | 0.6 | 0.4 | |
F6 | NP-1907/TBPH | 16.6-18.1 | <0.05 | - | 2.0 | 1.2 | 1.2 | 1.0 |
F7 | NP-2017 | 11.8-13.0 | - | - | 8.5 | 4.9 | 3.1 | 3.8 |
F8 | 11.8 | - | - | 0.4 | - | - | - | |
F9 | 10.0-11.1 | - | - | 1.0 | 0.6 | - | - | |
F10 | 8.1-9.1 | 0.1 | 0.1 | - | - | - | - | |
F11 | MOH | 6.3-7.1 | 3.6 | 2.4 | - | - | - | - |
F12 | 4.9-5.5 | 0.1 | <0.05 | - | - | - | - | |
F13 | 4.6 | <0.05 | <0.05 | - | - | - | - | |
F14 | 2.9 | 0.2 | 0.1 | - | - | - | - | |
F15 | 2.4 | <0.05 | 0.1 | - | - | - | - | |
#: sum of 0 - 24 h and 24 - 48 h sampling |
Table 7: Metabolites identified in the urine of rats administered 10 mg/kg bw test item labelled with MOH
Sex | male | female | |||||||
Test group | 3 | 4 | |||||||
Fraction | Retention time | % in sample | % of dose | % in sample | % of dose | ||||
0-8 h | 8-24 h | 0-8 h | 8-24 h | 0-8 h | 8-24 h | 0-8 h | 8-24 h | ||
U2 | 2.5-2.6 | 58.6 | 68.0 | 0.2 | 0.7 | 83.9 | 62.9 | 0.3 | 0.4 |
U1 | 3.2-3.3 | 41.4 | 32.0 | 0.2 | 0.3 | 16.2 | 37.1 | 0.1 | 0.2 |
Applicant's summary and conclusion
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.