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EC number: 617-298-9 | CAS number: 82097-50-5
- 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
Dermal absorption
Administrative data
- Endpoint:
- dermal absorption in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 24 Oct 2011 to 01 Nov 2011
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 012
- Report date:
- 2012
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 428 (Skin Absorption: In Vitro Method)
- Version / remarks:
- 2004
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- 2-(2-chloroethoxy)-N-[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)carbamoyl]benzene-1-sulfonamide
- EC Number:
- 617-298-9
- Cas Number:
- 82097-50-5
- Molecular formula:
- C14H16ClN5O5S
- IUPAC Name:
- 2-(2-chloroethoxy)-N-[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)carbamoyl]benzene-1-sulfonamide
Constituent 1
- Radiolabelling:
- yes
Administration / exposure
- Type of coverage:
- open
- Vehicle:
- water
- Duration of exposure:
- 24 hours
- Doses:
- - 33.3 % w/w aqueous slurry, nominally containing 66.7 g/kg
- 1/444 w/w dilutions, nominally containing 0.15 g/kg
- 1/888 w/w dilutions, nominally containing 0.075 g/kg
Results and discussion
Percutaneous absorptionopen allclose all
- Time point:
- 24 h
- Concentrate / Dilution:
- concentrate
- Dose:
- 33 % (w/w) , corresponding to 67.3 g substance/kg
- Parameter:
- percentage
- Absorption:
- 0.04 %
- Remarks on result:
- other: dermal absorption = (stratum corneum (tape strips 3-5) + remaining epidermis + receptor fluid) + k * SD
- Time point:
- 24 h
- Concentrate / Dilution:
- dilution
- Dose:
- 1/444 (w/w), corresponding to 0.168 g substance/kg
- Parameter:
- percentage
- Absorption:
- 1.8 %
- Remarks on result:
- other: dermal absorption = (stratum corneum (tape strips 3-5) + remaining epidermis + receptor fluid) + k * SD
- Time point:
- 24 h
- Concentrate / Dilution:
- dilution
- Dose:
- 1/888 (w/w), corresponding to 0.086 g substance/kg
- Parameter:
- percentage
- Absorption:
- 4.4 %
- Remarks on result:
- other: dermal absorption = (stratum corneum (tape strips 3-5) + remaining epidermis + receptor fluid) + k * SD
Any other information on results incl. tables
STABILITY IN THE FORMULATIONS
(14C)-labelled test substance, when formulated as a 66.7 g/kg, 0.15 g/kg and 0.075 g/kg formulation, was shown to be stable by HPLC for a period of 1 day, which is a period of time longer than that used in the study.
Radiochemical purities of greater than 97 % were seen in all dose preparations both prior to application and one day post dose preparation.
PARTICLE SIZE
Particle size analysis of the dose preparations confirmed that the mean particle sizes were 6.95 μm (2.5 – 17.5 μm range), 7.43 μm (2.5 – 20 μm range) and 7.26 μm (2.5 – 21.25 μm range) for the 33.3 % w/w aqueous slurry and the 1/444 w/w and 1/888 w/w aqueous dilutions, respectively.
Table 1. Individual Distribution of the test substance from the 33.3 % w/w Aqueous Slurry of the Formulation Concentrate in the Test System
Test Compartment | Percentage of Dose Recovered (%) | |||||
Cell 31 | Cell 33 | Cell 35 | Cell 36 | Cell 38 | Cell 39 | |
Donor chamber | 0.004 | 0.002 | 0 | 0.011 | 0.02 | 0.02 |
Skin wash | 108 | 99.9 | 114 | 110 | 113 | 109 |
Stratum corneum (Tape strips 1 & 2) | 0.008 | 0.018 | 0.013 | 0.009 | 0.017 | 0.008 |
Stratum corneum (Tape strips 3 - 5) | 0.004 | 0.007 | 0.005 | 0.006 | 0.01 | NS |
Remaining epidermis | 0.007 | 0.02 | 0.009 | 0.01 | 0.007 | 0.044 |
Receptor fluid | 0.012 | 0 | 0.007 | 0.001 | 0.004 | 0.002 |
Total recovered | 108 | 100 | 114 | 110 | 113 | 109 |
Dermal absorption per cell | 0.023 | 0.027 | 0.017 | 0.046 |
Stratum corneum = amount in tape strips; Remaining epidermis = epidermal tissue remaining after tape stripping
* (Cell 35 and 38 were excluded in the calculation of the mean absorption due to high recovery).
Table 2. Individual Distribution of the test substance from the 1/444 w/w Aqueous Slurry of the Formulation Concentrate in the Test System
Test Compartment | Percentage of Dose Recovered (%) | |||||
Cell 1 | Cell 2 | Cell 3 | Cell 6 | Cell 7 | Cell 15 | |
Donor chamber | 0 | 2.62 | 0 | 0.238 | 0 | 0 |
Skin wash | 97.5 | 101 | 100 | 103 | 99.4 | 105 |
Stratum corneum (Tape strips 1 & 2) | 0.183 | 0.231 | 0.423 | 0.287 | 0.315 | 0.064* |
Stratum corneum (Tape strips 3 - 5) | 0.183 | 0.358 | 0.367 | 0.127 | 0.166 | 0.025* |
Remaining epidermis | 1.57 | 1.44 | 0.973 | 0.804 | 0.553 | 0.284 |
Receptor fluid | 1.35 | 0.149 | 0.075 | 0.139 | 0.094 | 0.056 |
Total recovered | 101 | 106 | 102 | 104 | 100 | 105 |
Dermal absorption per cell | 3.103 | 1.947 | 1.415 | 1.070 | 0.813 | 0.340 |
Stratum corneum = amount in tape strips; Remaining epidermis = epidermal tissue remaining after tape stripping
Table 3. Individual Distribution of the test substance from the 1/888 w/w Aqueous Slurry of the Formulation Concentrate in the Test System
Test Compartment | Percentage of Dose Recovered (%) | |||||
Cell 5 | Cell 9 | Cell 10 | Cell 19 | Cell 26 | Cell 28 | |
Donor chamber | 0.000* | 0.817 | 0 | 0 | 0 | 0 |
Skin wash | 106 | 102 | 93.9 | 93.4 | 103 | 99.9 |
Stratum corneum (Tape strips 1 & 2) | 0.487 | NS | 0.989 | 0.534 | 0.172 | 0.381 |
Stratum corneum (Tape strips 3 - 5) | 0.841 | NS | 0.985 | 0.414 | 0.210 | 0.457 |
Remaining epidermis | 2.10 | 3.00 | 4.22 | 2.74 | 0.724 | 1.28 |
Receptor fluid | 0.086 | 0.194 | 0.078 | 0.141 | 0.143 | 0.224 |
Total recovered | 110 | 106 | 100 | 97.2 | 104 | 102 |
Dermal absorption per cell | 3.027 | 3.194 | 5.283 | 3.295 | 1.077 | 1.961 |
Stratum corneum = amount in tape strips; Remaining epidermis = epidermal tissue remaining after tape stripping
Applicant's summary and conclusion
- Conclusions:
- The penetration of the test substance from a 33.3 % w/w (corresponding to 67.3 g substance/kg) slurry, 1/444 w/w (corresponding to 0.168 g substance/kg) and 1/888 w/w (corresponding to 0.086 substance/kg) aqueous spray strength dilutions of the concentrate slurry, through human epidermis is very slow and the vast majority of the applied dose could be removed by gentle skin washing after 24 hours. The overall absorption of the test substance over 24 hours was 0.04, 1.8, and 4.4 %, for the 33.3 % w/w slurry, 1/444 w/w dilution, and 1/888 w/w dilution, respectively. These data predict that the systemic exposure to the test substance following dermal contact with this formulation would be minimal.
- Executive summary:
The dermal absorption and distribution of the test substance from formulation concentrate was measured in human skin in a study conducted according to OECD TG 428 following GLP. Doses of (14C)-test substance were applied as a 33.3 % w/w aqueous slurry of the formulation concentrate (nominally, 66.7 g/kg) and as 1/444 w/w (nominally, 0.15 g/kg) and 1/888 w/w (nominally, 0.075 g/kg) aqueous spray strength aqueous dilutions of the slurry. The doses were applied at 10 μL/cm2 and left unoccluded for an exposure period of 24 hours. The absorption process was followed by taking samples of the receptor fluid (50 % v/v ethanol/water) at recorded intervals throughout the exposure period. The distribution of the test substance within the test system and a 24 hour absorption profile were determined, using liquid scintillation counting (LSC). The absorbed (systemically available) dose is calculated based on EFSA guidance on dermal absorption (2017). Based on the fact that the study has a duration of 24 hours, < 75 % of the permeation occurs in the first half of the study, and that the tape strips were analysed individually, the tape stips 1 + 2 were excluded from the absorption calculation. Dermal absorption = % in receptor fluid + % in skin sample.
For the 33.3 % w/w aqueous slurry of the formulation concentrate slurry, the mean total recovery was 109 % of the dose applied. The overall dermal absorption of the test substance from the 33.3 % w/w aqueous slurry of the formulation concentrate through human epidermis was 0.04 % during the 24 hour exposure period. The amount absorbed at 24 hours was 0.028 μg/cm² (0.004 % of the dose applied). The amounts absorbed at 6, 8 and 12 hours were 0.021 μg/cm² (0.003 %), 0.021 μg/cm² (0.003 %) and 0.030 μg/cm² (0.004 %), respectively. These values were below the limit of quantitation (0.039 μg/cm², 0.006 %). The vast majority of the applied test substance (mean 109 %) was washed off the skin at 24 hours.
For the 1/444 w/w aqueous dilution of the formulation concentrate slurry, the mean total recovery was 104 % of the dose applied. The overall dermal absorption of the test substance from the 1/444 w/w aqueous dilution of the formulation concentrate slurry through human epidermis was 1.8 % during the 24 hour exposure period. The amount absorbed at 24 hours was 0.0017 μg/cm² (0.103 % of the dose applied). The amounts absorbed at 6, 8 and 12 hours were 0.0005 μg/cm² (0.032 %), 0.0007 μg/cm² (0.040 %) and 0.0008 μg/cm² (0.050 %), respectively. The values for 6 and 8 hours were below the limit of quantitation (0.0008 μg/cm², 0.047 %).The vast majority of the applied test substance (mean 102 %) was washed off the skin at 24 hours.
For the 1/888 w/w aqueous dilution of the formulation concentrate slurry, the mean total recovery was 103 % of the dose applied. The overall dermal absorption of the test substance from the 1/888 w/w aqueous dilution of the formulation concentrate slurry through human epidermis was 4.4 % during the 24 hour exposure period. The amount absorbed at 24 hours was 0.0012 μg/cm² (0.143 % of the dose applied). The amounts absorbed at 6, 8 and 12 hours were 0.0007 μg/cm² (0.080 %), 0.0007 μg/cm² (0.086 %) and 0.0009 μg/cm² (0.102 %), respectively. The values for 6 and 8 hours were below the limit of quantitation (0.0008 μg/cm², 0.090 %).The vast majority of the applied test substance (mean 99.8 %) was washed off the skin at 24 hours.
The penetration of the test substance from a 33.3 % w/w slurry, 1/444 w/w and 1/888 w/w aqueous spray strength dilutions of the concentrate slurry, through human epidermis is very slow and the vast majority of the applied dose could be removed by gentle skin washing after 24 hours. The overall absorption of the test substance over 24 hours was 0.04, 1.8, and 4.4 %, for the 33.3 % w/w slurry, 1/444 w/w dilution, and 1/888 w/w dilution, respectively. These data predict that the systemic exposure to the test substance following dermal contact with this formulation would be minimal.
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