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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 265-512-0 | CAS number: 65140-91-2
- 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:
- 1983
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Meets generally accepted scientific standards, well documented and acceptable for assessment.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 983
- Report date:
- 1983
Materials and methods
- Objective of study:
- other: absorption, distribution, excretion
- Principles of method if other than guideline:
- Different groups of rats were treated with 14C-labeled test material followed by analysis of excrements, blood, organs and carcass to determine absorption, distribution and excretion of the test material.
- GLP compliance:
- yes
Test material
- Reference substance name:
- Calcium diethyl bis[[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl]phosphonate]
- EC Number:
- 265-512-0
- EC Name:
- Calcium diethyl bis[[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl]phosphonate]
- Cas Number:
- 65140-91-2
- Molecular formula:
- C17 H29 O4 P. 1/2Ca
- IUPAC Name:
- calcium diethyl bis[[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl]phosphonate]
- Details on test material:
- - Radiochemical purity: >99% (determination by radio thin layer chromatography)
- Specific activity (if radiolabelling): 59.388 µCi/mg
Constituent 1
- Radiolabelling:
- yes
- Remarks:
- 14C-radiolabelling
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Wiga GmbH, 8741 Sulzfeld/Germany
- Weight at study initiation: 172-182 g
- Housing: For 7 days before administration of the test substance and during the experimental phase the control and test rats were housed separately in metabolism cages.
- Individual metabolism cages: yes
- Diet: Dr. Rupprecht Schott Nachf. GmbH + Co., Hamburg/Germany, Art.-No. 253, ca. 22 g/day (except the day before administration of test substance, only 8 g)
- Water: tap water, ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-1
- Humidity (%): 55+/-5
- Photoperiod: 12 hrs dark / 12 hrs light
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: A mixture of equal parts by weight of 1,2-dihydroxypropane and tap water.
- Details on exposure:
- The radioactive solution as well as the non-labelled solution were prepared shortly before administration to the test animals. Calculated amounts of 14-C-labelled or non-labelled test material were weighed in the glass vessels of an Ultrasonic homogeniser and dissolved in the defined amounts of the test vehicle at 30°C within 30 minutes. The rats were given the 14-C-labelled antioxidant Irganox 1425 in solution by stomach tube. First, each test animal was weighed shortly before treatment and the actual volume for intubation determined by its body weight, the formerly defined doses and by the concentration of the 14-C labelled test substance in the solution. The calculated volume of solution for intubation was administered with a tuberculin syringe via an infusion cannula with olive (stomach tube) directly into the stomach of the rat. To determine the precise amount of 14C- labelled Irganox 1425 intubated into the rats, the exact weight of the empty and full syringe was determined, and after application the empty syringe was reweighed. The rats of the test group received an total oral dose of 10.88 mg/kg bw (corresponding to 636 µCi/kg bw) of 14-C-labelled Irganox 1425. The rats of the control group received in the same way an average oral dose of about 10.5 mg per kg body weight of the non-labelled antioxidant Irganox 1425, in a mixture of 1.2-dihydroxypropane and tap water.
- Duration and frequency of treatment / exposure:
- Single oral exposures.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
Control groups: 10.5 mg/kg bw non-labeled test substance
Test groups:
Distribution: 10.88 mg/kg bw labeled test substance (corresponding to 636 µCi/kg bw)
Absorption: 10.7 mg/kg bw labeled test substance (corresponding to 623 µCi/kg bw)
Excretion: 8.8 and 0.53 mg/kg bw labeled test substance (corresponding to 630 and 31 µCi/kg bw, respectively)
- No. of animals per sex per dose / concentration:
- Distribution: 5 test and 2 control animals
Absorption: 6 test and 2 control animals
Excretion: 6 low dose and 6 high dose test animals, 2 control animals - Control animals:
- yes
Results and discussion
Main ADME resultsopen allclose all
- Type:
- absorption
- Results:
- Only small amounts are absorbed from the gastrointestinal tracts into the blood, reaching a maximum within the first and second hour after administration.
- Type:
- distribution
- Results:
- Absorbed radioactivity was concentrated significantly but only temporarily in the livers, virtually completely eliminated during period of study.
- Type:
- excretion
- Results:
- Within 168 hours after oral administration an average of 87.6% and 86.3% (high dose and low dose, respectively) of the dose was excreted, mainly via the feces (85.4% and 84.9%). Further amounts of radioactivity were exhaled.
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- The absorption of the test substance from the gastrointestinal tract of the rat has a maximum between the first and second hour after oral administration. In this period, the average equivalent concentration amounted to about 0.78 µg test substance per g blood. The subsequent decrease of the average equivalent concentration of the test substance in the blood of the rats is clearly shown by the values at 48 and 168 hours after oral administration of 0.029 and 0.005 µg, resp., test substance per g blood (for details see table 1 "Any other information on results").
- Details on distribution in tissues:
- Autoradiograms showed that the substance was absorbed only in small portions from the gastrointestinal tracts, was concentrated significantly only in the liver of the test rats and only temporarily. These radioactivities and the clearly lower concentrations over the remaining organs and tissues of the test animals were almost completely eliminated during the progress of experiment.
The gastrointestinal tracts of the rats killed at 168 hours contained on average about 0.01% of the dose. As a consequence of the enormous elimination of the C-labelled test substance and/or its metabolites in faeces and urine, the results show that only small amounts of radioactivity were found in the blood, the organs, tissue samples and in the residual carcass. At the time of sacrifice, the blood of the rats contained an average of less than 0.01% of the dose and about 0.06% and 0.1% were present in the residual carcasses of high dose and low dose animals, respectively. The blood, organs and tissue samples taken at the time of sacrifice and the residual carcass of the rats from the high dose group contained average equivalent concentrations from 3.7 (testicles) to 29.5 ng test substance (liver) per g, whereas the blood, organs, tissue samples and the residual carcass of the rats from the low dose animals contained only average equivalent concentrations from 0.3 (blood) to 2.7 ng test substance (liver) per g (for details see table 2 and table 3 "Any other information on results").
- Details on excretion:
- An average of 85.4% and 84.9% of the given radioactivities were eliminated in the faeces by rats from the high dose and loe dose, respectively, within 168 hours after oral administration of the 14C-labelled test substance. In the same interval, an average of 2.2% and 1.4% of the radioactivity amounts orally administered in form of the 14C-labelled test substance were found in the urine of the rats. According to these results, the rats, excreted, an average of 87.6% (high dose) and 86.3% (low dose) within 168 hours after oral administration. As pre-tests showed, the test rats exhaled further amounts of radioactivity.
Any other information on results incl. tables
Table 1: Radioactivities, the average relative and equivalent concentrations of the orally administered test substance in the blood of rats after different time points.
|
Test substance |
|
Radioactivity of blood [nCi/g] at time after administration [h] |
||||||||||||
|
Radioactivity |
Dose |
0.25 |
0.5 |
1 |
2 |
4 |
6 |
12 |
24 |
48 |
72 |
120 |
168 |
|
|
[µCi] |
[µCi/g bw] |
[mg/kg bw] |
|
|
|
|
|
|
|
|
|
|
|
|
Average |
114.12 |
0.6228 |
10.711 |
17.39 |
36.52 |
45.67 |
41.09 |
17.06 |
12.67 |
5.988 |
4.066 |
1.714 |
0.9623 |
0.4406 |
0.2786 |
Standard deviation |
3.4 |
0.018 |
0.32 |
9.84 |
23.55 |
32.79 |
25.70 |
3.6 |
3.62 |
1.54 |
1.42 |
1.33 |
0.53 |
0.14 |
0.07 |
Relative standard deviation (%) |
3.0 |
3.0 |
3.0 |
56.6 |
64.5 |
71.8 |
62.5 |
21.3 |
28.6 |
25.7 |
34.8 |
77.6 |
54.8 |
32.0 |
27.9 |
Average relative concentration |
|
|
|
27.780 |
58.339 |
72.955 |
65.636 |
27.249 |
20.233 |
9.565 |
6.496 |
2.738 |
1.537 |
0.704 |
0.4455 |
Average equivalent concentration |
|
|
|
0.2976 |
0.6249 |
0.7814 |
0.7030 |
0.2919 |
0.2167 |
0.1025 |
0.0696 |
0.0293 |
0.0165 |
0.0075 |
0.0048 |
Relative concentration = average measured radioactivity per g test material/administered radioactivity per g body weight at time of intubation
Equivalent concentration = Relative concentration * dose administered (mg/g bw) * 1000 [µg/g test material]
Table 2: Excretion of radioactivity (%) in urine and feces by rats given 14C-labeled test material by intubation.
|
|
|
Average excreted radioactivity amounts [%(sd)] |
||||||||
Group |
Number of animals |
Route of excretion |
0-3 h |
3-6 h |
6-24 h |
24-48 h |
48-72 h |
72-96 h |
96-120 h |
120-144 h |
144-168 h |
high dose |
6 |
urine |
0.31 (0.26) |
0.26 (0.08) |
1.41 (1.46) |
0.17 (0.11) |
0.04 (0.02) |
0.01 (0.01) |
0.01 |
0.01 |
0.01 |
feces |
0.03 (0.03) |
76.99 (5.12) |
7.95 (3.65) |
0.36 (0.24) |
0.07 (0.01) |
0.03 (<0.01) |
0.01 (<0.01) |
0.01 |
|||
low dose |
6 |
urine |
0.17 (0.09) |
0.24 (0.1) |
0.72 (0.12) |
0.18 (0.10) |
0.04 (0.01) |
0.03 (0.01) |
0.03 (0.01) |
0.02 |
<0.01 |
feces |
|
67.95 (6.13) |
16.05 (4.39) |
0.74 (0.43) |
0.12 (0.05) |
0.04 (0.02) |
0.02 (0.01) |
0.02 (0.01) |
Table 3. Summary of the average radioactivity amounts in %, of the average relative (P) and equivalent concentrations (C) after 168 h.
tissue | radioactivity amount (%) | average relative concentration (P) | equivalent concentration (C) (ng/g) | |||
group | high dose | low dose | high dose | low dose | high dose | low dose |
urine | 2.2 | 1.4 | ||||
feces | 85.39 | 84.94 | ||||
GI tract | 0.01 | 0.01 | ||||
blood | < 0.01 | < 0.01 | 0.53 | 0.66 | 4.6 | 0.3 |
liver | 0.02 | 0.03 | 3.39 | 6.29 | 29.5 | 2.7 |
kidneys | < 0.01 | < 0.01 | 1.29 | 2.07 | 11.3 | 0.9 |
testicles | < 0.01 | < 0.01 | 0.43 | 0.88 | 3.7 | 0.4 |
muscle | < 0.01 | < 0.01 | 0.63 | 1.16 | 5.5 | 0.5 |
fat | < 0.01 | 0.01 | 2.38 | 3.95 | 20.7 | 1.7 |
residual carcass | 0.06 | 0.1 | 0.72 | 1.34 | 6.2 | 0.6 |
recovered radioactivity | 87.68 | 86.49 |
Relative concentration P = average measured radioactivity per g test material/administered radioactivity per g body weight at time of intubation
Equivalent concentration C = Relative concentration * dose administered (mg/g bw) * 1000 [µg/g test material]
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): no bioaccumulation potential based on study results
The orally given test material and its possible metabolites are retained for only a limited time in male rats and are preferentially excreted in the feces, but also via the kidneys and by respiration.
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.