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EC number: 262-104-4 | CAS number: 60207-90-1
- 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 vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1986
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 986
- Report date:
- 1986
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: Biochemistry Protocol 68-861
- Principles of method if other than guideline:
- The objective of this study was to determine the magnitude of skin absorption of up to a 10-hour exposure period at three different rates of application. This study was done utilising a 14C-test substance 3.6EC formulated product in an aqueous suspension. The percent of the dose absorbed, excreted and the amount remaining on the skin were used to estimate the magnitude of dermal absorption and to calculate a total 14C-balance. This study was conducted in accordance with Biochemistry Protocol 68-861.
- GLP compliance:
- yes
Test material
- Reference substance name:
- 1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole
- EC Number:
- 262-104-4
- EC Name:
- 1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole
- Cas Number:
- 60207-90-1
- Molecular formula:
- C15H17Cl2N3O2
- IUPAC Name:
- 1-{[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl}-1H-1,2,4-triazole
Constituent 1
- Radiolabelling:
- yes
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Remarks:
- Harlan
- Sex:
- male
Administration / exposure
- Type of coverage:
- unoccluded
- Vehicle:
- water
- Duration of exposure:
- 10-hour
- Doses:
- 0.1, 1.0 and 10.0 mg/rat, equivalent to 0.01, 0.1 and 1.0 mg/square centimeter, respectively.
- No. of animals per group:
- 12
- Control animals:
- no
Results and discussion
- Absorption in different matrices:
- The rate of absorption of 14C-test substance is inversely related to the dosage level (as the dosage level increases, the total percent absorbed decreases). After a 4-hour period, the total amount absorbed was 52.0 %, 48.5 % and 34.4 % for the low, mid and high dose levels, respectively. After a 10-hour period, the total amount absorbed was 71.0 % and 42.0 % for the low and mid dose levels, respectively. In this study, dermal absorption = % in blood + % in carcass + % in skin + % in urine + % in faeces + % in cage wash
- Total recovery:
- The range of total 14C recovery mean values for the three dosage levels and sacrifice times was from 63.7 % to 119.9 %
Percutaneous absorptionopen allclose all
- Time point:
- 2 h
- Concentrate / Dilution:
- dilution
- Dose:
- 0.11 mg/Rat
- Parameter:
- percentage
- Absorption:
- 53.1 %
- Remarks on result:
- other: 0.11 mg/Rat
- Time point:
- 4 h
- Concentrate / Dilution:
- dilution
- Dose:
- 0.11 mg/Rat
- Parameter:
- percentage
- Absorption:
- 52 %
- Remarks on result:
- other: 0.11 mg/Rat
- Time point:
- 10 h
- Concentrate / Dilution:
- dilution
- Dose:
- 0.11 mg/Rat
- Parameter:
- percentage
- Absorption:
- 71 %
- Remarks on result:
- other: 0.11 mg/Rat
- Time point:
- 24 h
- Concentrate / Dilution:
- dilution
- Dose:
- 0.11 mg/Rat
- Parameter:
- percentage
- Absorption:
- 66.5 %
- Remarks on result:
- other: 0.11 mg/Rat
- Time point:
- 82 h
- Concentrate / Dilution:
- dilution
- Dose:
- 0.12 mg/Rat
- Parameter:
- percentage
- Absorption:
- 57.1 %
- Remarks on result:
- other: 0.12 mg/Rat
- Time point:
- 96 h
- Concentrate / Dilution:
- dilution
- Dose:
- 0.11 mg/Rat
- Parameter:
- percentage
- Absorption:
- 65.8 %
- Remarks on result:
- other: 0.11 mg/Rat
- Time point:
- 2 h
- Concentrate / Dilution:
- dilution
- Dose:
- 1.1 mg/Rat
- Parameter:
- percentage
- Absorption:
- 28.4 %
- Remarks on result:
- other: 1.1 mg/Rat
- Time point:
- 4 h
- Concentrate / Dilution:
- dilution
- Dose:
- 1.2 mg/Rat
- Parameter:
- percentage
- Absorption:
- 48.5 %
- Remarks on result:
- other: 1.2 mg/Rat
- Time point:
- 10 h
- Concentrate / Dilution:
- dilution
- Dose:
- 1.2 mg/Rat
- Parameter:
- percentage
- Absorption:
- 42 %
- Remarks on result:
- other: 1.2 mg/Rat
- Time point:
- 96 h
- Concentrate / Dilution:
- dilution
- Dose:
- 1.3 mg/Rat
- Parameter:
- percentage
- Absorption:
- 43.5 %
- Remarks on result:
- other: 1.3 mg/Rat
- Time point:
- 2 h
- Concentrate / Dilution:
- dilution
- Dose:
- 8.6 mg/Rat
- Parameter:
- percentage
- Absorption:
- 37.9 %
- Remarks on result:
- other: 8.6 mg/Rat
- Time point:
- 4 h
- Concentrate / Dilution:
- dilution
- Dose:
- 8.6 mg/Rat
- Parameter:
- percentage
- Absorption:
- 34.4 %
- Remarks on result:
- other: 8.6 mg/Rat
- Time point:
- 24 h
- Concentrate / Dilution:
- dilution
- Dose:
- 8.7 mg/Rat
- Parameter:
- percentage
- Absorption:
- 38 %
- Remarks on result:
- other: 8.7 mg/Rat
- Time point:
- 82 h
- Concentrate / Dilution:
- dilution
- Dose:
- 8.9 mg/Rat
- Parameter:
- percentage
- Absorption:
- 42.9 %
- Remarks on result:
- other: 8.9 mg/Rat
- Time point:
- 96 h
- Concentrate / Dilution:
- dilution
- Dose:
- 9.6 mg/Rat
- Parameter:
- percentage
- Absorption:
- 76.7 %
- Remarks on result:
- other: 9.6 mg/Rat
Any other information on results incl. tables
RECOVERIES
The range of total 14C recovery mean values for the three dosage levels and sacrifice times was from 63.67 % to 119.92 %. In line with the EFSA guidance on dermal absorption (2017) only the recoveries between 90 and 110% were used for further assessment.
ABSORPTION
The rate of absorption of 14C-test substance is inversely related to the dosage level (as the dosage level increases, the total percent absorbed decreases). After a 10-hour period, the total amount absorbed was 71.0 % and 42.0 % for the low and mid dose levels respectively, while the high dose level at this time point did not show acceptable recovery levels for further assessment. Within each dose level, the dermal absorption results varied enormously between the individual animals. At the low dose level, the dermal absorption ranged from 25.17 to 64.61 %, with an average and standard deviation of respectively 52.86 % and 9.96. At the mid dose level, the dermal absorption ranged from 24.97 to 44.28 %, with an average and standard deviation of respectively 33.64 % and 6.30. And at the high dose level, the dermal absorption ranged from 26.34 to 60.23 %, with an average and standard deviation of respectively 34.20 % and 8.16.
EXCRETION
For all dose levels less than 20 % of the dose was excreted in a 10-hour period. The main route of excretion was in the urine.
SKIN RESIDUES
Ten hours after treatment, total skin residue values were on average 50.0 % (Skin I, Skin II, soap rinse and water rinse) for the low dose and 79.8 % for the mid-dose level. A large proportion of the radioactivity on the skin was removed by the soap and water rinses; on average 33.9 and 54.4 % of the applied dose for the low and mid dosage levels, respectively. For these levels, about 70 % of the radioactivity on the skin could be removed with soap and water rinses. Except for the 4-hour time point at the high dose leveland time points and measurments performed after 24 hours of dosing, the amount of radioactivity in Skin Sections I were greater than Skin Sections II indicating that the applied dose did not migrate appreciably from the treated area during the washing process. The amount of radioactivity remaining in the skin as residue is possibly available for further absorption and these values were considered as part of the total percent absorbed.
Table 1. Low Dose (0.11 mg/Rat): Summary of absorption
2 hour dosing | Percentage of Dose | |||
ANIMAL: | #1 | #2 | #3 | #4 |
Blood | 0.30 | 0.31 | 0.14 | 0.15 |
Carcass | 16.99 | 15.77 | 12.66 | 7.61 |
Skin I | 20.63 | 18.13 | 16.61 | 14.50 |
Skin II | 2.25 | 2.41 | 3.65 | 2.05 |
Urine | 1.83 | 1.39 | 0.00 | 0.33 |
Faeces | 0.00 | 0.00 | 0.00 | 0.02 |
Bandage rinse | 2.44 | 0.76 | 2.48 | 3.16 |
Bridge rinse | 0.87 | 2.90 | 4.39 | 2.43 |
Soap rinse | 52.00 | 45.54 | 44.67 | 39.11 |
Water rinse | 5.29 | 4.54 | 9.31 | 5.00 |
Gauze A | 5.19 | 11.71 | 15.46 | 27.39 |
Gauze B | 0.18 | 0.23 | 0.15 | 0.22 |
Paper | 0.06 | 2.07 | 0.53 | 2.85 |
Paper rinse | 2.38 | 4.09 | 9.16 | 1.28 |
Cage wash | 0.31 | 1.23 | 0.71 | 0.51 |
Recovery | 110.72 | 111.08# | 119.92# | 106.61 |
Total absorbed | 42.31 | 39.24 | 33.77 | 25.17 |
Average | 33.7 | |||
SD | 12.1 | |||
k-factor | 1.6 | |||
Absorp% | 53.1 |
# data not taken into account, outside the acceptable recovery range
Table II. Low Dose (0.11 mg/Rat): Summary of absorption
4 hour dosing | Percentage of Dose | |||
ANIMAL: | #1 | #2 | #3 | #4 |
Blood | 0.15 | 0.11 | 0.14 | 0.07 |
Carcass | 9.53 | 7.83 | 12.00 | 7.30 |
Skin I | 31.40 | 27.64 | 29.00 | 29.40 |
Skin II | 3.29 | 9.25 | 8.02 | 8.93 |
Urine | 1.45 | 1.18 | 1.22 | 0.29 |
Faeces | 0.01 | 0.00 | 0.01 | 1.00 |
Bandage rinse | 0.53 | 1.00 | 0.75 | 1.00 |
Bridge rinse | 0.99 | 0.99 | 0.65 | 0.86 |
Soap rinse | 51.40 | 26.36 | 39.77 | 46.75 |
Water rinse | 11.59 | 12.82 | 11.33 | 8.06 |
Gauze A | 1.66 | 0.90 | 1.26 | 1.16 |
Gauze B | 0.53 | 0.65 | 0.49 | 0.34 |
Paper | 0.15 | 0.11 | 0.02 | 0.08 |
Paper rinse | 3.83 | 3.25 | 0.83 | 2.12 |
Cage wash | 0.43 | 0.56 | 0.50 | 0.33 |
Recovery | 116.94# | 92.65 | 105.99 | 107.69 |
Total absorbed | 46.26 | 46.57 | 50.89 | 47.32 |
Average | 48.3 | |||
SD | 2.3 | |||
k-factor | 1.6 | |||
Absorp% | 52.0 |
# data not taken into account, outside the acceptable recovery range
Table III. Low Dose (0.11 mg/Rat): Summary of absorption
10 hour dosing | Percentage of Dose |
|
| |
ANIMAL: | #1 | #2 | #3 | #4 |
Blood | 0.31 | 0.28 | 0.16 | 0.28 |
Carcass | 37.48 | 30.36 | 20.55 | 32.38 |
Skin I | 10.92 | 14.61 | 15.69 | 6.59 |
Skin II | 1.38 | 2.57 | 2.48 | 1.88 |
Urine | 13.00 | 7.46 | 3.87 | 11.99 |
Faeces | 0.00 | 0.01 | 0.16 | 0.26 |
Bandage rinse | 5.99 | 0.60 | 3.85 | 0.65 |
Bridge rinse | 1.86 | 3.48 | <0.00 | 0.59 |
Soap rinse | 31.54 | 24.53 | 30.85 | 23.67 |
Water rinse | 3.71 | 2.89 | 7.87 | 2.39 |
Gauze A | 1.07 | 5.14 | 2.92 | 3.03 |
Gauze B | 0.12 | 0.18 | 0.21 | 0.10 |
Paper | 0.04 | 1.46 | 0.18 | 0.02 |
Paper rinse | 1.61 | 5.33 | 2.44 | 1.08 |
Cage wash | 0.76 | 0.91 | 0.50 | 0.89 |
Recovery | 109.79 | 99.81 | 91.73 | 85.80# |
Total absorbed | 63.85 | 56.2 | 43.41 | 54.27 |
Average | 54.5 | |||
SD | 10.3 | |||
k-factor | 1.6 | |||
Absorp% | 71.0 |
# data not taken into account, outside the acceptable recovery range
Table IV. Low Dose (0.12 mg/Rat): Animal data
24 hour dosing | Percentage of Dose | |||
ANIMAL: | #1 | #2 | #3 | #4 |
Blood | 0.21 | 0.14 | 0.23 | 0.18 |
Carcass | 26.63 | 19.22 | 19.23 | 10.09 |
Skin I | 7.48 | 6.89 | 2.64 | 14.63 |
Skin II | 1.56 | 1.68 | 2.22 | 1.69 |
Urine | 20.10 | 18.89 | 13.98 | 16.37 |
Faeces | 11.54 | 13.86 | 8.15 | 10.89 |
Bandage rinse | 0.53 | 0.56 | 0.67 | 1.18 |
Bridge rinse | 1.14 | 0.94 | 0.64 | 2.21 |
Soap rinse | 36.36 | 39.10 | 37.22 | 32.88 |
Water rinse | 2.51 | 2.31 | 3.15 | 3.40 |
Gauze A | 1.77 | 1.66 | 4.26 | 2.24 |
Gauze B | 0.58 | 0.56 | 0.94 | 0.06 |
Paper | 0.05 | 0.04 | 0.15 | 0.07 |
Paper rinse | 1.16 | 1.62 | 2.06 | 3.32 |
Cage wash | 1.73 | 1.91 | 2.38 | 1.29 |
Recovery | 113.35# | 109.38 | 97.92 | 100.50 |
Total absorbed | 69.25 | 62.59 | 48.83 | 55.14 |
Average | 55.5 | |||
SD | 6.9 | |||
k-factor | 1.6 | |||
Absorp% | 66.5 |
# data not taken into account, outside the acceptable recovery range
Table V. Low Dose (0.11 mg/Rat): Animal data
82 hour dosing | Percentage of Dose | |||
ANIMAL: | #1 | #2 | #3 | #4 |
Blood | 0.05 | 0.00 | 0.00 | 0.00 |
Carcass | 1.51 | 1.57 | 1.45 | 1.56 |
Skin I | 2.55 | 1.75 | 2.33 | 2.70 |
Skin II | 5.55 | 3.80 | 3.15 | 1.69 |
Urine 10 | 5.53 | 5.25 | 4.10 | 5.65 |
Urine 34 | 10.87 | 11.37 | 10.48 | 11.72 |
Urine 58 | 3.56 | 4.38 | 3.66 | 3.64 |
Urine 82 | 1.32 | 1.80 | 1.54 | 1.54 |
Faeces 10 | 0.00 | 0.13 | 0.25 | 1.69 |
Faeces 34 | 12.57 | 15.19 | 12.10 | 13.98 |
Faeces 58 | 4.11 | 3.78 | 4.00 | 3.93 |
Faeces 82 | 2.21 | 2.05 | 0.82 | 1.41 |
Bandage Rinse | 0.78 | 0.00 | 0.86 | 2.02 |
Bridge Rinse | 0.94 | 2.00 | 2.17 | 2.46 |
Soap Rinse I | 46.31 | 41.20 | 49.42 | 37.89 |
Water Rinse I | 4.13 | 4.33 | 5.19 | 5.09 |
Soap Rinse II | 1.52 | 1.13 | 1.09 | 0.88 |
Water Rinse II | 0.75 | 0.70 | 0.74 | 0.65 |
Paper Rinse | 2.26 | 0.63 | 0.00 | 1.59 |
Gauze A | 2.61 | 3.21 | 3.95 | 2.41 |
Gauze B | 0.27 | 0.35 | 0.26 | 0.24 |
Gauze C | 0.05 | 0.03 | 0.06 | 0.05 |
Gauze D | 0.03 | 0.02 | 0.02 | 0.02 |
Cage Wash I | 0.94 | 0.80 | 0.60 | 0.76 |
Cage Wash II | 1.24 | 2.01 | 1.00 | 1.01 |
Paper | 0.06 | 0.05 | 0.04 | 0.08 |
Recovery | 111.72 | 107.53 | 109.28 | 104.66 |
Total absorbed | 52.01 | 53.88 | 45.48 | 51.28 |
Average | 50.21 | |||
SD | 4.30 | |||
k-factor | 1.60 | |||
Absorp% | 57.1 |
Table VI Low Dose (0.11 mg/Rat): Animal data
96 hour dosing | Percentage of Dose | |||
ANIMAL: | #1 | #2 | #3 | #4 |
Blood | 0.00 | 0.09 | 0.00 | 0.00 |
Carcass | 1.06 | 1.36 | 2.13 | 1.28 |
Skin I | 1.61 | 1.80 | 5.39 | 2.80 |
Skin II | 0.92 | 1.37 | 2.11 | 2.80 |
Urine 24 | 21.84 | 17.23 | 11.76 | 17.01 |
Urine 48 | 0.80 | 7.81 | 9.33 | 9.88 |
Urine 72 | 6.44 | 2.55 | 3.17 | 2.81 |
Urine 96 | 0.00 | 1.02 | 2.27 | 1.04 |
Faeces 24 | 18.64 | 12.01 | 4.84 | 12.25 |
Faeces 48 | 6.90 | 11.50 | 11.41 | 7.84 |
Faeces 72 | 1.43 | 2.13 | 2.48 | 2.88 |
Faeces 96 | 0.64 | 0.90 | 1.22 | 0.87 |
Bandage Rinse | 0.61 | 0.00 | 0.80 | 0.60 |
Bridge Rinse | 2.58 | 4.47 | 3.31 | 0.00 |
Soap Rinse I | 11.27 | 18.53 | 25.30 | 17.80 |
Water Rinse I | 3.08 | 3.08 | 5.27 | 3.97 |
Soap Rinse II | 1.07 | 0.99 | 1.11 | 0.63 |
Water Rinse II | 0.58 | 0.62 | 1.01 | 0.63 |
Paper Rinse | 6.59 | 10.87 | 1.84 | 7.65 |
Gauze A | 5.48 | 2.67 | 4.53 | 3.89 |
Gauze B | 0.22 | 0.09 | 0.80 | 0.38 |
Gauze C | 0.04 | 0.03 | 0.07 | 0.03 |
Gauze D | 0.01 | 0.02 | 0.02 | 0.02 |
Cage Wash I | 1.48 | 0.78 | 1.31 | 0.88 |
Cage Wash II | 2.85 | 0.66 | 1.64 | 0.73 |
Paper | 0.46 | 0.31 | 1.18 | 0.95 |
Total Percent Recovered | 96.60 | 102.89 | 104.30 | 99.62 |
Recovery | 96.60 | 102.89 | 104.30 | 99.62 |
Total absorbed | 64.61 | 61.21 | 59.06 | 63.07 |
Average | 61.99 | |||
SD | 2.40 | |||
k-factor | 1.60 | |||
Absorp% | 65.8 |
Table VII. Mid Dose (1.1 mg/Rat): Summary of absorption
2 hour dosing | Percentage of Dose | |||
ANIMAL: | #1 | #2 | #3 | #4 |
Blood | 0.09 | 0.05 | 0.04 | 0.02 |
Carcass | 3.61 | 2.77 | 1.73 | 1.70 |
Skin I | 18.53 | 17.51 | 18.81 | 16.68 |
Skin II | 5.05 | 3.84 | 6.06 | 7.00 |
Urine | 0.30 | 0.00 | 0.09 | 0.00 |
Faeces | 0.01 | 0.00 | 0.00 | 0.00 |
Bandage rinse | 0.25 | 0.64 | 0.30 | 0.86 |
Bridge rinse | 0.09 | 0.10 | 0.28 | 0.16 |
Soap rinse | 71.28 | 68.87 | 68.68 | 61.58 |
Water rinse | 4.28 | 4.85 | 5.25 | 5.40 |
Gauze A | 5.34 | 5.72 | 5.15 | 3.18 |
Gauze B | 0.15 | 0.20 | 0.13 | 0.11 |
Paper | 0.02 | 0.07 | 0.11 | 0.21 |
Paper rinse | 0.35 | 0.49 | 0.83 | 0.76 |
Cage wash | 0.28 | 0.80 | 0.07 | 0.12 |
Recovery | 109.63 | 105.91 | 107.53 | 97.78 |
Total absorbed | 27.87 | 24.97 | 26.803 | 25.52 |
Average | 26.3 | |||
SD | 1.3 | |||
k-factor | 1.6 | |||
Absorp% | 28.4 |
Table VIII. Mid Dose (1.2 mg/Rat): Summary of absorption
4 hour dosing | Percentage of Dose | |||
ANIMAL: | #1 | #2 | #3 | #4 |
Blood | 0.04 | 0.03 | 0.05 | 0.03 |
Carcass | 0.31 | 2.32 | 3.94 | 3.36 |
Skin I | 13.21 | 11.97 | 10.80 | 13.60 |
Skin II | 2.52 | 2.50 | 2.40 | 4.87 |
Urine | 24.05 | 9.32 | 27.02 | 9.24 |
Faeces | 0.01 | 1.00 | 0.00 | 0.00 |
Bandage rinse | 0.06 | 0.14 | 0.07 | 0.36 |
Bridge rinse | 4.52 | 4.75 | 4.22 | 1.24 |
Soap rinse | 51.81 | 35.91 | 39.43 | 50.17 |
Water rinse | 4.17 | 4.44 | 4.75 | 6.22 |
Gauze A | 4.81 | 5.39 | 4.50 | 3.47 |
Gauze B | 0.26 | 0.33 | 0.04 | 0.11 |
Paper | 0.68 | 1.23 | 0.30 | 0.09 |
Paper rinse | 8.41 | 17.28 | 13.21 | 4.03 |
Cage wash | 0.10 | 0.10 | 0.07 | 0.07 |
Recovery | 114.96# | 96.71 | 110.80 | 96.86 |
Total absorbed | 40.24 | 27.24 | 44.28 | 31.17 |
Average | 34.2 | |||
SD | 8.9 | |||
k-factor | 1.6 | |||
Absorp% | 48.5 |
# data not taken into account, outside the acceptable recovery range
Table IX Mid Dose (1.2 mg/Rat): Summary of absorption
10 hour dosing | Percentage of Dose |
|
| |
ANIMAL: | #1 | #2 | #3 | #4 |
Blood | 0.09 | 0.10 | 0.09 | 0.09 |
Carcass | 9.09 | 9.31 | 8.18 | 9.60 |
Skin I | 18.06 | 21.23 | 19.86 | 19.53 |
Skin II | 3.74 | 7.81 | 5.17 | 4.55 |
Urine | 2.37 | 2.07 | 1.51 | 2.21 |
Faeces | 0.00 | 0.00 | 0.00 | 0.03 |
Bandage rinse | 0.18 | 0.15 | 2.97 | 2.98 |
Bridge rinse | 1.07 | 0.15 | 0.53 | 0.11 |
Soap rinse | 52.84 | 48.08 | 52.94 | 44.54 |
Water rinse | 4.33 | 4.43 | 4.87 | 3.11 |
Gauze A | 4.54 | 2.33 | 2.01 | 6.59 |
Gauze B | 0.21 | 0.31 | 0.16 | 0.06 |
Paper | 0.08 | 0.04 | 0.01 | 0.02 |
Paper rinse | 2.53 | 1.66 | 0.45 | 0.47 |
Cage wash | 1.80 | 0.90 | 1.12 | 1.47 |
Recovery | 100.93 | 98.57 | 99.87 | 95.36 |
Total absorbed | 35.15 | 41.42 | 35.93 | 37.48 |
Average | 37.5 | |||
SD | 2.8 | |||
k-factor | 1.6 | |||
Absorp% | 42.0 |
Table X. Mid Dose (1.3 mg/Rat): Animal data
24 hour dosing | Percentage of Dose | |||
ANIMAL: | #1 | #2 | #3 | #4 |
Blood | 0.05 | 0.09 | 0.07 | 0.10 |
Carcass | 6.53 | 6.57 | 7.28 | 9.03 |
Skin I | 9.50 | 12.67 | 19.95 | 16.04 |
Skin II | 1.46 | 2.09 | 2.07 | 3.90 |
Urine | 4.28 | 0.79 | 0.24 | 0.19 |
Faeces | 1.74 | 1.24 | 1.30 | 1.36 |
Bandage rinse | 1.02 | 0.18 | 0.00 | 1.96 |
Bridge rinse | 5.86 | 1.57 | 1.84 | 0.63 |
Soap rinse | 25.01 | 35.81 | 34.02 | 22.95 |
Water rinse | 5.04 | 3.17 | 3.06 | 19.58 |
Gauze A | 1.62 | 2.97 | 5.82 | 2.54 |
Gauze B | 0.29 | 0.16 | 0.27 | 0.18 |
Paper | 2.29 | 0.42 | 0.21 | 2.61 |
Paper rinse | 16.58 | 15.01 | 4.97 | 0.28 |
Cage wash | 0.27 | 0.45 | 1.54 | 0.18 |
Recovery | 81.54# | 83.19# | 82.64# | 81.53# |
Total absorbed | 23.83 | 23.9 | 32.45 | 30.80 |
# data not taken into account, outside the acceptable recovery range
Table XI. Mid Dose (1.2 mg/Rat): Animal data
82 hour dosing | Percentage of Dose | |||
ANIMAL: | #1 | #2 | #3 | #4 |
Blood | 0.01 | 0.01 | 0.01 | 0.02 |
Carcass | 0.82 | 0.81 | 1.05 | 0.84 |
Skin I | 2.31 | 2.45 | 1.95 | 1.63 |
Skin II | 1.16 | 2.08 | 2.82 | 0.37 |
Urine 10 | 2.35 | 0.56 | 2.69 | 2.12 |
Urine 34 | 7.68 | 3.69 | 8.03 | 7.83 |
Urine 58 | 2.38 | 2.38 | 2.69 | 3.45 |
Urine 82 | 0.80 | 1.04 | 1.19 | 1.06 |
Faeces 10 | 0.04 | 0.01 | 0.02 | 0.11 |
Faeces 34 | 5.15 | 3.42 | 6.97 | 5.74 |
Faeces 58 | 1.81 | 1.58 | 1.75 | 2.60 |
Faeces 82 | 0.68 | 0.84 | 0.87 | 0.70 |
Bandage Rinse | 0.61 | 0.12 | 0.11 | 0.10 |
Bridge Rinse | 1.36 | 8.41 | 2.66 | 3.99 |
Soap Rinse I | 33.36 | 34.80 | 31.93 | 38.13 |
Water Rinse I | 4.74 | 2.62 | 3.06 | 3.95 |
Soap Rinse II | 0.60 | 0.86 | 0.54 | 0.21 |
Water Rinse II | 0.35 | 0.42 | 0.21 | 0.11 |
Paper Rinse | 15.78 | 19.24 | 5.58 | 9.42 |
Gauze A | 1.93 | 0.91 | 5.82 | 2.71 |
Gauze B | 0.12 | 0.06 | 0.10 | 0.10 |
Gauze C | 0.06 | 0.04 | 0.03 | 0.01 |
Gauze D | 0.07 | 0.03 | 0.02 | 0.01 |
Cage Wash I | 0.10 | 0.11 | 0.23 | 0.21 |
Cage Wash II | 0.32 | 0.27 | 0.53 | 0.40 |
Paper | 0.31 | 1.51 | 3.12 | 0.60 |
Recovery | 84.90# | 88.27# | 83.98# | 86.42# |
Total absorbed | 25.61 | 19.25 | 30.80 | 27.08 |
# data not taken into account, outside the acceptable recovery range
Table XII. Mid Dose (1.3 mg/Rat): Animal data
96 hour dosing | Percentage of Dose | |||
ANIMAL: | #1 | #2 | #3 | #4 |
Blood | 0.02 | 0.01 | 0.01 | 0.02 |
Carcass | 2.20 | 1.34 | 1.14 | 1.35 |
Skin I | 2.01 | 2.74 | 2.77 | 3.34 |
Skin II | 4.31 | 2.47 | 2.97 | 1.47 |
Urine 24 | 7.66 | 6.71 | 5.64 | 5.51 |
Urine 48 | 6.56 | 7.39 | 5.83 | 5.72 |
Urine 72 | 3.35 | 2.06 | 2.34 | 2.88 |
Urine 96 | 1.21 | 1.16 | 1.08 | 1.41 |
Faeces 24 | 3.13 | 4.37 | 1.12 | 2.00 |
Faeces 48 | 5.52 | 6.76 | 7.29 | 4.43 |
Faeces 72 | 2.45 | 2.65 | 1.48 | 2.57 |
Faeces 96 | 1.07 | 1.56 | 0.90 | 1.31 |
Bandage Rinse | 0.44 | 1.27 | 0.78 | 0.60 |
Bridge Rinse | 1.44 | 0.19 | 0.27 | 2.10 |
Soap Rinse I | 46.89 | 42.95 | 48.90 | 50.06 |
Water Rinse I | 4.87 | 4.02 | 5.18 | 4.18 |
Soap Rinse II | 0.42 | 0.20 | 0.85 | 1.00 |
Water Rinse II | 0.23 | 0.16 | 0.44 | 0.64 |
Paper Rinse | 1.05 | 1.06 | 2.61 | 1.06 |
Gauze A | 2.25 | 3.88 | 3.00 | 1.12 |
Gauze B | 0.15 | 0.20 | 0.12 | 0.05 |
Gauze C | 0.01 | 0.02 | 0.05 | 0.05 |
Gauze D | 0.01 | 0.01 | 0.03 | 0.02 |
Cage Wash I | 0.20 | 0.61 | 0.27 | 0.14 |
Cage Wash II | 0.52 | 0.63 | 1.05 | 1.15 1.15 |
Paper | 0.05 | 0.05 | 0.10 | 0.04 |
Total Percent Recovered | 98.02 | 94.47 | 96.22 | 94.22 |
Recovery | 98.02 | 94.47 | 96.22 | 93.07 |
Total absorbed | 40.21 | 40.46 | 33.89 | 32.15 |
Average | 36.68 | |||
SD | 4.28 | |||
k-factor | 1.60 | |||
Absorp% | 43.53 |
Table XIII. High Dose (8.6 mg/Rat): Summary of absorption
2 hour dosing | Percentage of Dose | |||
ANIMAL: | #1 | #2 | #3 | #4 |
Blood | 0.03 | 0.30 | 0.03 | 0.02 |
Carcass | 1.51 | 1.13 | 1.43 | 1.21 |
Skin I | 24.47 | 22.13 | 23.70 | 33.82 |
Skin II | 2.51 | 3.05 | 2.85 | 2.17 |
Urine | 0.10 | 0.00 | 0.00 | 0.03 |
Faeces | 0.00 | 0.00 | 0.00 | 0.00 |
Bandage rinse | 0.80 | 0.26 | 0.15 | 0.12 |
Bridge rinse | 0.89 | 2.32 | 1.66 | 2.66 |
Soap rinse | 69.27 | 57.94 | 58.93 | 51.09 |
Water rinse | 5.97 | 4.92 | 6.80 | 5.82 |
Gauze A | 1.08 | 1.99 | 3.40 | 4.83 |
Gauze B | 0.09 | 1.08 | 0.14 | 0.10 |
Paper | 0.03 | 0.08 | 0.10 | 0.03 |
Paper rinse | 1.45 | 5.65 | 0.73 | 0.97 |
Cage wash | 0.05 | 1.00 | 0.07 | 0.12 |
Recovery | 108.25 | 101.85 | 99.99 | 102.99 |
Total absorbed | 28.67 | 27.61 | 28.08 | 37.37 |
Average | 30.4 | |||
SD | 4.6 | |||
k-factor | 1.6 | |||
Absorp% | 37.9 |
Table XIV. High Dose (8.6 mg/Rat): Summary of absorption
4 hour dosing | Percentage of Dose | |||
ANIMAL: | #1 | #2 | #3 | #4 |
Blood | 0.03 | 0.06 | 0.05 | 0.04 |
Carcass | 1.32 | 1.29 | 0.06 | 1.43 |
Skin I | 5.13 | 5.08 | 4.89 | 9.92 |
Skin II | 24.39 | 21.99 | 27.71 | 5.07 |
Urine | 0.29 | 0.14 | 0.16 | 0.16 |
Faeces | 0.01 | 0.00 | 0.00 | 0.00 |
Bandage rinse | 0.48 | 0.91 | 0.72 | 3.01 |
Bridge rinse | 0.10 | 0.13 | 0.38 | 1.00 |
Soap rinse | 56.97 | 53.50 | 48.52 | 33.96 |
Water rinse | 5.27 | 5.54 | 4.82 | 5.37 |
Gauze A | 3.92 | 2.72 | 3.39 | 2.44 |
Gauze B | 0.18 | 0.12 | 0.08 | 0.44 |
Paper | 0.04 | 0.06 | 0.08 | 0.07 |
Paper rinse | 1.77 | 1.45 | 2.93 | 0.40 |
Cage wash | 0.08 | 0.06 | 0.07 | 0.36 |
Recovery | 99.98 | 93.05 | 93.86 | 63.67# |
Total absorbed | 31.25 | 28.62 | 32.94 | 16.98 |
Average | 30.9 | |||
SD | 2.2 | |||
k-factor | 1.6 | |||
Absorp% | 34.4 |
# data not taken into account, outside the acceptable recovery range
Table X. High Dose (9.2 mg/Rat): Summary of absorption
10 hour dosing | Percentage of Dose |
|
| |
ANIMAL: | #1 | #2 | #3 | #4 |
Blood | 0.02 | 0.08 | 0.08 | 0.08 |
Carcass | 2.75 | 3.76 | 3.73 | 4.74 |
Skin I | 28.42 | 16.85 | 21.09 | 21.01 |
Skin II | 3.24 | 2.39 | 2.38 | 2.56 |
Urine | 0.60 | 0.91 | 1.19 | 1.15 |
Faeces | 0.01 | 0.05 | 0.03 | 0.00 |
Bandage rinse | 3.22 | 0.13 | 0.17 | 0.59 |
Bridge rinse | 0.88 | 4.96 | 6.12 | 3.20 |
Soap rinse | 26.89 | 32.84 | 37.88 | 29.05 |
Water rinse | 3.59 | 4.00 | 3.34 | 5.29 |
Gauze A | 2.41 | 1.96 | 2.38 | 3.08 |
Gauze B | 0.10 | 0.16 | 0.08 | 0.15 |
Paper | 9.51 | 7.91 | 0.14 | 0.34 |
Paper rinse | 5.83 | 6.48 | 8.93 | 17.22 |
Cage wash | 0.07 | 0.07 | 0.12 | 0.11 |
Recovery | 87.54# | 82.55# | 87.66# | 88.57# |
Total absorbed | 35.11 | 24.11 | 28.62 | 29.65 |
# data not taken into account, outside the acceptable recovery range
Table XVI. High Dose (8.7 mg/Rat): Summary of absorption
24 hour dosing | Percentage of Dose | |||
ANIMAL: | #1 | #2 | #3 | #4 |
Blood | 0.03 | 0.03 | 0.03 | 0.02 |
Carcass | 1.51 | 1.13 | 1.43 | 1.21 |
Skin I | 24.47 | 22.13 | 23.70 | 33.82 |
Skin II | 2.51 | 3.05 | 2.85 | 2.17 |
Urine | 0.10 | 0.00 | 0.00 | 0.03 |
Faeces | 0.00 | 0.00 | 0.00 | 0.00 |
Bandage rinse | 0.80 | 0.26 | 0.15 | 0.12 |
Bridge rinse | 0.89 | 2.32 | 1.66 | 2.66 |
Soap rinse | 69.27 | 57.94 | 58.93 | 51.09 |
Water rinse | 5.97 | 4.92 | 6.80 | 5.82 |
Gauze A | 1.08 | 1.99 | 3.40 | 4.83 |
Gauze B | 0.09 | 1.08 | 0.14 | 0.10 |
Paper | 0.03 | 0.08 | 0.01 | 0.03 |
Paper rinse | 1.45 | 5.65 | 0.73 | 0.97 |
Cage wash | 0.05 | 0.00 | 0.07 | 0.12 |
Recovery | 108.25 | 100.58 | 99.90 | 102.99 |
Total absorbed | 28.67 | 26.34 | 28.08 | 37.37 |
Average | 30.12 | |||
SD | 4.94 | |||
k-factor | 1.60 | |||
Absorp% | 38.0 |
Table XVII. High Dose (8.9 mg/Rat): Animal data
82 hour dosing | Percentage of Dose | |||
ANIMAL: | #1 | #2 | #3 | #4 |
Blood | 0.02 | 0.03 | 0.03 | 0.03 |
Carcass | 1.26 | 2.02 | 2.01 | 2.04 |
Skin I | 0.70 | 2.96 | 2.32 | 2.54 |
Skin II | 4.06 | 4.44 | 3.39 | 3.77 |
Urine 10 | 1.19 | 0.74 | 0.81 | 0.62 |
Urine 34 | 9.53 | 6.14 | 8.97 | 7.26 |
Urine 58 | 4.28 | 6.69 | 7.89 | 6.58 |
Urine 82 | 1.74 | 3.54 | 2.74 | 2.57 |
Faeces 10 | 0.04 | 0.01 | 0.00 | 0.00 |
Faeces 34 | 5.77 | 3.13 | 2.83 | 2.65 |
Faeces 58 | 3.33 | 5.11 | 6.46 | 5.83 |
Faeces 82 | 1.40 | 3.24 | 3.14 | 2.12 |
Bandage Rinse | 0.47 | 0.54 | 0.31 | 0.17 |
Bridge Rinse | 2.20 | 0.34 | 0.28 | 0.68 |
Soap Rinse I | 40.79 | 41.54 | 41.65 | 41.15 |
Water Rinse I | 7.05 | 4.72 | 3.78 | 4.05 |
Soap Rinse II | 0.28 | 1.46 | 1.52 | 0.70 |
Water Rinse II | 0.22 | 0.52 | 0.61 | 0.45 |
Paper Rinse | 7.07 | 5.61 | 3.52 | 6.66 |
Gauze A | 2.11 | 2.08 | 1.96 | 3.44 |
Gauze B | 0.12 | 0.12 | 0.12 | 0.09 |
Gauze C | 0.01 | 0.02 | 0.04 | 0.02 |
Gauze D | 0.02 | 0.02 | 0.01 | 0.01 |
Cage Wash I | 0.13 | 0.09 | 0.06 | 0.18 |
Cage Wash II | 0.88 | 0.89 | 0.89 | 1.02 |
Paper | 0.21 | 0.16 | 0.21 | 0.12 |
Recovery | 94.88 | 96.16 | 95.55 | 94.75 |
Total absorbed | 34.33 | 39.03 | 41.54 | 37.21 |
Average | 38.03 | |||
SD | 3.04 | |||
k-factor | 1.60 | |||
Absorp% | 42.9 |
Table XVIII. High Dose (9.6 mg/Rat): Animal data
96 hour dosing | Percentage of Dose | |||
ANIMAL: | #1 | #2 | #3 | #4 |
Blood | 0.02 | 0.02 | 0.02 | 0.02 |
Carcass | 1.70 | 1.62 | 1.97 | 1.35 |
Skin I | 8.53 | 14.31 | 5.25 | 5.76 |
Skin II | 1.29 | 7.49 | 4.26 | 3.35 |
Urine 24 | 2.75 | 16.43 | 5.04 | 3.77 |
Urine 48 | 5.53 | 6.72 | 7.60 | 6.56 |
Urine 72 | 3.77 | 3.10 | 4.83 | 4.45 |
Urine 96 | 1.45 | 1.19 | 1.55 | 1.96 |
Faeces 24 | 0.91 | 1.52 | 0.87 | 1.10 |
Faeces 48 | 3.54 | 3.91 | 4.04 | 3.45 |
Faeces 72 | 2.76 | 2.52 | 3.45 | 3.58 |
Faeces 96 | 1.24 | 0.77 | 0.98 | 1.19 |
Bandage Rinse | 0.56 | 0.62 | 0.12 | 1.15 |
Bridge Rinse | 3 .31 | 3.36 | 4.38 | 2.36 |
Soap Rinse I | 14.85 | 10.58 | 19.04 | 11.70 |
Water Rinse I | 10.67 | 2.98 | 2.59 | 2.90 |
Soap Rinse II | 0.39 | 0.49 | 0.30 | 0.59 |
Water Rinse II | 0.25 | 0.55 | 0.16 | 0.43 |
Paper Rinse | 24.16 | 18.32 | 0.56 | 0.42 |
Gauze A | 6.41 | 1.52 | 3.49 | 3.36 |
Gauze B | 0.07 | 0.08 | 0.78 | 0.21 |
Gauze C | 0.01 | 0.03 | 0.04 | 0.02 |
Gauze D | 0.01 | 0.05 | 0.01 | 0.03 |
Cage Wash I | 0.21 | 0.28 | 0.15 | 0.16 |
Cage Wash II | 0.44 | 0.35 | 0.23 | 0.47 |
Paper | 3.47 | 3.83 | 15.42 | 14.96 |
Recovery | 94.99 | 102.64 | 87.13# | 75.30# |
Total absorbed | 34.14 | 60.23 | 40.24 | 37.17 |
Average | 47.19 | |||
SD | 18.45 | |||
k-factor | 1.60 | |||
Absorp% | 76.7 |
# data not taken into account, outside the acceptable recovery range
Applicant's summary and conclusion
- Conclusions:
- The rate of absorption of 14C-test substance is inversely related to the dosage level for 0.01, 0.1 and 1.0mg/sq.cm dose. After a 10-hour period, the total amount absorbed (blood + carcass + skin + urine + faeces + cage wash) was 71.0 % and 42.0 % for the low and mid dose levels respectively, while the high dose level at this time point did not show acceptable recovery levels for further assessment. Within each dose level, the dermal absorption results varied enormously between the individual animals. At the low dose level, the dermal absorption ranged from 25.17 to 64.61 %, with an average and standard deviation of respectively 52.86 % and 9.96. At the mid dose level, the dermal absorption ranged from 24.97 to 44.28 %, with an average and standard deviation of respectively 33.64 % and 6.30. And at the high dose level, the dermal absorption ranged from 26.34 to 60.23 %, with an average and standard deviation of respectively 34.20 % and 8.16. The dermal absorption calculations were in line with EFSA guidance.
- Executive summary:
A dermal absorption study was conducted utilising a simulated 3.6EC formulation of 14C-test substance on male rats over a 2, 4 and 10-hour test period at three dosage levels (0.1, 1.0 and 10.0 mg/rat). The test area was 10 sq. cm (2.5 cm by 4.0 cm) located on the upper back portion of the rat. Resulting doses were based on areas of 0.01, 0.10, 1.0 mg/sq. cm for the low, mid and high dosage levels. This study was conducted according to the Biochemistry Protocol 68-861 and did not follow GLP criteria.
The range of total 14C recovery mean values for the three dosage levels and sacrifice times was from 63.67 % to 119.92 %. As per the EFSA guidance on dermal absorption (2017) only the recoveries between 90 and 110% were used for further assessment.
The rate of absorption of 14C-test substance is inversely related to the dosage level (as the dosage level increases, the total percent absorbed decreases). After a 10-hour period, the total amount absorbed was 71.0 % and 42.0 % for the low and mid dose levels respectively, while the high dose level at this time point did not show acceptable recovery levels for further assessment. Within each dose level, the dermal absorption results varied enormously between the individual animals. At the low dose level, the dermal absorption ranged from 25.17 to 64.61 %, with an average and standard deviation of respectively 52.86 % and 9.96. At the mid dose level, the dermal absorption ranged from 24.97 to 44.28 %, with an average and standard deviation of respectively 33.64 % and 6.30. And at the high dose level, the dermal absorption ranged from 26.34 to 60.23 %, with an average and standard deviation of respectively 34.20 % and 8.16.
For all dose levels less than 20 % of the dose was excreted in a 10-hour period. The main route of excretion was in the urine.
The dermal absorption calculations were in line with EFSA guidance.
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