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EC number: 400-820-2 | CAS number: 84268-33-7
- 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
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1991-1992
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: OECD Guideline Study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 992
- Report date:
- 1992
Materials and methods
- Objective of study:
- absorption
- distribution
- excretion
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 417 (Toxicokinetics)
- GLP compliance:
- yes
- Remarks:
- RCC, Itingen, Switzerland
Test material
- Reference substance name:
- -
- EC Number:
- 400-820-2
- EC Name:
- -
- Cas Number:
- 84268-33-7
- Molecular formula:
- C20 H23 N3 O3
- IUPAC Name:
- methyl 3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoate
- Details on test material:
- - Physical state: white solid
- Analytical purity: 99%
- Lot/batch No.: OPZ 288/1 U (unlabeled) and CFQ 6155 (labeled)
- Radiochemical purity (if radiolabelling): 98.3 - 99.0 % on December 17, 1990
- Specific activity (if radiolabelling): 56 µCi/mg (2.07 MBq/mg) or 19.8 mCi/mmol (0.733 GBq/mmol)
- Locations of the label (if radiolabelling): phenolic ring U-C14
- Storage condition of test material: dark, -20°C
Constituent 1
- Radiolabelling:
- yes
- Remarks:
- 14-C
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: BRL Biological Research Laboratories Ltd., Wolferstrasse 4, CH-4414 Fuellinsdorf/Switzerland
- Age at study initiation: Males: 6 weeks / Females: 7-8 weeks
- Weight at study initiation: 145 - 201 g for males and from 150 - 190 g for females
- Fasting period before study: overnight
- Housing: 3/cage
- Individual metabolism cages: yes
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Five to six days to laboratory environment, including 1-3 days to metabolism cages.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 -25
- Humidity (%): 40 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: acetone, cremophor and 0.9% NaCl
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: Based on the high target dose level of 10 mg/kg, a rat body weight of 0.2 kg and a target administration volume of 1 ml/100g rat, an aliquot of 134 µL of the acetonic solution of the test article (corresponding to about 2.0 mg substance) was mixed with 100 mg CREMOPHOR EL (BASF, Ludwigshafen/Germany) and 1765 µL 0.9 % NaCl. The suspension obtained was turbid and not enough homogeneous. Therefore, another aliquot of 134µL of the acetonic solution of the test article was first suspended in about 200 mg CREMOPHOR before being mixed with
1665µL 0.9 % NaCl. A clear and homogeneous suspension was obtained. In conclusion, the high dose level (1 mg test article/100 g rat) was efficiently
formulated in about 67µL acetone, 100 mg CREMOPHOR and 833µL NaCl 0.9 %. Consequently, the low dose level was formulated identically. - Duration and frequency of treatment / exposure:
- single treatment
Doses / concentrations
- Remarks:
- Doses / Concentrations:
1 mg/kg = 56 µCi/mg = 2.07 MBq/mg
10 mg/kg = 20 µCi/mg = 0.74 MBq/mg
- No. of animals per sex per dose / concentration:
- 10
- Control animals:
- no
- Details on study design:
- - Dose selection rationale:
- Rationale for animal assignment (if not random): - Details on dosing and sampling:
- PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled (delete / add / specify): urine, faeces, blood, plasma, organ/tissues, cage washes
- Time and frequency of sampling: Urine/Feces: It was taken 8, 24, 48, 72, 96, 120, 144 and 168 hours after the administration. Additionally, at
sampling intervals of 8 and 24 hours, metabolism cages were rinsed with a small amount of bidistilled water (about 2 ml) to remove remaining droplets of urine which were added to the initially sampled urine. Final volumes were noted. Feces was collected at room temperature 24, 48, 72, 96, 120, 144 and 168 hours after the administration. Fresh weights were noted.
Blood: After 168 hours, animals were killed by carbon dioxide.
Organs/Tissues and Residual Carcass: The following organs and tissues were taken after 168 hours: Heart, lung, liver, stomach (contents were separately determined), spleen, kidney, muscle, bones (femur), brain, fat, pancreas, intestinal tract (with contents), adrenal glands, gonads (ovary and uterus or testicle and epididymes), thyroid gland, skin (backregion) and residual carcass.
Cage Wash: At the end of the study, the cages were washed with water/acetone (50+50, v/v). The washing solutions were then used for determination of remaining radioactivity.
Results and discussion
Main ADME resultsopen allclose all
- Type:
- absorption
- Results:
- low but significant amounts from the gastro-intestinal tract
- Type:
- distribution
- Results:
- Negligible amounts (<0.1%) of radioactivity were found in organs/tissues, intestinal tract, blood and residual carcass
- Type:
- excretion
- Results:
- Excretion proceeded mainly via the faeces and urine. In both cases > 87% of the dose was excreted within the first 24 hours.
Toxicokinetic / pharmacokinetic studies
- Details on distribution in tissues:
- At the low dose level, In both sexes, very low or negligible (0.1 % - <0.05 %) amounts of radioactivity were found at 168 hours after the administration in organs/tissues, blood, intestinal tract and residual carcass.
At the high dose level, negligible or very low amounts of radioactivity (<0.05 % - 0.1 %) were found in organs/ tissues, blood, intestinal tract and residual carcass.
At 168 hours after low dose level administration for both sexes, very low residual radioactivity levels were found in the excretory organs liver (0.007 - 0.009 µg/g) and kidney (0.006 - 0.007 µg/g). In spleen, residual radioactivity levels (0.005 µg/g) approached the limit of quantitation. In females, residual radioactivity levels in blood, plasma, adrenal glands, brain, intestinal tract with contents and stomach contents (0.003 - 0.007 µg/g) also approached the limit of quantitation. In all other organs/ tissues, intestinal tract with contents (only for males) and residual carcass, residual radioactivity levels were negligible, i.e. at or below the limit of quantitation.
At a ten times higher dose level, residual radioactivity levels at 168 hours in the excretory organs liver (0.058 - 0.074 µg/g), kidney (0.036 - 0.064 µg/g) and intestinal tract with contents (0.014 µg/g - 0.022 µg/g) were about 4-7 times the limit of quantitation. Residual radioactivity levels in blood/plasma, spleen, fat, skin backregion, stomach contents (only females) and residual carcass ranged from 0.009 µg/g (residual carcass; males) to 0.062 µg/g (blood; females) and amounted to 2-4 times the limit of quantitation. In the remaining organs/tissues, radioactivity levels were negligible or below two times the limit of quantitation.
- Details on excretion:
- At the low dose level, excretion of radioactivity via the urine represented after 168 hours, on average, 4.8 % and 6.1 % of the radioactivity administered
in males and females, respectively. Already 24 hours after the administration, urinary excretion accounted for 4.5 % (males) and 5.8 % (females). Excretion proceeded mainly via the feces and accounted after 168 hours, on average, for 96.8 % (males) and 95.8 % (females) of the radioactivity administered. Already after 24 hours, fecal excretion amounted to 87.8 % and 86.9 % in males and females, respectively (see table 1). Together with the cage wash (0.4 % - 0.5 %), total excreted radioactivity amounted to 102.0 % (males) and 102.4 % (females).
A similar excretion pattern was found at a ten times higher dose level in both sexes. After 168 hours, urinary excretion accounted for 5.1 % and 8.8 % of the radioactivity administered in males and females, respectively. Already after 24 hours, urinary excretion amounted to 4.8 % (males) and 8.6 % (females). After 168 hours, fecal excretion accounted, on average, for 93.1 (males) and 92.3 % (females). Again, the major amount (83.1 % in males and 85.2 % in females) was excreted within the first 24 hours. Together with the cage wash (0.6 % - 0.3 %), total excreted radioactivity amounted to 98.8 % and 101.5 % in males and females, respectively.
Any other information on results incl. tables
Table 1: Elimination after a single dose of 1 or 10 mg/kg bw
Dose level |
1 mg/kg bw |
10 mg/kg bw |
|||
Time after administration |
24h |
168h |
24h |
168h |
|
Males (n=5) |
Radioactivity in feces [%] |
87.8 |
96.8 |
83.1 |
93.1 |
Radioactivity in urine [%] |
4.5 |
4.8 |
4.8 |
5.1 |
|
Females (n=5) |
Radioactivity in feces [%] |
86.9 |
95.8 |
85.2 |
92.3 |
Radioactivity in urine [%] |
5.8 |
6.1 |
8.6 |
8.8 |
Table 2: Amount [mg CG 20-571 per g] of CG 20-571 in rat tissues 168 h after a single dose of 1 or 10 mg/kg bw
Dose |
1 mg/kg bw |
11 mg/kg bw |
|
Males and females |
liver |
0.008 |
0.058 – 0.074 |
kidney |
0.0065 |
0.036 – 0.064 |
|
spleen |
0.005 |
0.014 – 0.022 |
|
intestinal tract with contents |
|
0.014 – 0.022 |
|
Females only (values for males are lower and therefore not given) |
blood plasma adrenal glands brain intestinal tract + contents stomach contents |
0.007 0.005 0.005 0.003 0.003 0.003 |
0.062 0.042 0.017 0.008 0.022 0.018 |
spleen |
0.005 |
0.022 |
|
|
Uterus ovaries |
0.002* 0.002* |
0.018 0.012* |
Males only |
Testes epididymes |
0.002* 0.003* |
0.007* 0.011* |
*Mean level at or below the limit of quantitation
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.
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