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EC number: 619-372-6 | CAS number: 98730-04-2
- 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
Dermal absorption
Administrative data
- Endpoint:
- dermal absorption in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Biological phase April 1987 to May 1987; analytical phase May 1987 to July 1987
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Near-guideline study, available as unpublished report, no restrictions, fully adequate for assessment
Cross-reference
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 987
- Report date:
- 1987
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The dermal absorption of CGA154281 was determined over a 10 and 24 hour exposure period.
- GLP compliance:
- not specified
Test material
- Reference substance name:
- 2,2-dichloro-1-[(3R)-3-methyl-3,4-dihydro-2H-1,4-benzoxazin-4-yl]ethan-1-one; 2,2-dichloro-1-[(3S)-3-methyl-3,4-dihydro-2H-1,4-benzoxazin-4-yl]ethan-1-one
- EC Number:
- 619-372-6
- Cas Number:
- 98730-04-2
- Molecular formula:
- C11H11Cl2NO2
- IUPAC Name:
- 2,2-dichloro-1-[(3R)-3-methyl-3,4-dihydro-2H-1,4-benzoxazin-4-yl]ethan-1-one; 2,2-dichloro-1-[(3S)-3-methyl-3,4-dihydro-2H-1,4-benzoxazin-4-yl]ethan-1-one
Constituent 1
- Radiolabelling:
- yes
Test animals
- Species:
- rat
- Strain:
- other: Sprague Dawley CD®BR
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Portage, Michigan, USA
- Age at study initiation: approximately 50-54 days
- Weight at study initiation: 200-300 g
- Further details in IUCLID 7.1.1 Report no. 82016 (CGA154281/0240)
Administration / exposure
- Type of coverage:
- other: nonocclusive
- Vehicle:
- unchanged (no vehicle)
- Duration of exposure:
- Single
- Doses:
- 1, 10mg/rat
- No. of animals per group:
- 16
- Control animals:
- no
- Details on study design:
- DOSE PREPARATION
- Method for preparation of dose suspensions: the low dose was prepared by mixing 15.7 mg of 14C-CGA154281, 46.6 mg of blank formulant (EC) and 500 mg of non-labelled metolachlor, then suspending the mixture in 25 mL water. The high dose was prepared by mixing 31.5 mg of 14C-CGA154281, 31.5 mg of blank formulant (EC) and 1000 mg of non-labelled metolachlor, then suspending the mixture in 10 mL water. These suspensions simulate a typical metoachlor 7.8 EC formulation containing 2.8% 14C-CGA154281.
- Application: 50 µL of 1.0 mg/rat or 100 µL of 10.0 mg/rat were applied with a displacement pipette and spread over the apprication area. After 5-10 minutes the entire area was enclosed by a nonocclusive covering.
TEST SITE
- Area of exposure: 10 cm2 (4.0 x 2.5 cm)
- Type of cover / wrap if used: a Stomahesive bandage was used to form a wall around the edge of the application area. After dosing, aluminium foil was glued onto the Stomahesive across the diameter of the dose area, to support filter paper that was then glued onto the Stomahesive; this enclosed the entire application area.
- Time intervals for shavings or clippings: on the day prior to dose application
SITE PROTECTION: yes, on the day of dosing, rear leg hobbles were fitted to prevent disturbance of the application site
REMOVAL OF TEST SUBSTANCE
- Washing procedures and type of cleansing agent: the treated skin area was washed twice with a detergent solution and rinsed with deionised water. Each washing was done with a sterile gauze square which was then placed in 50 mL of methanol.
- Time after start of exposure: 2, 4, 10 or 24 hours after application
SAMPLE COLLECTION
- Collection of blood: yes, at termination. Blood was collected at termination from the inferior vena cava.
- Collection of urine and faeces: a single continuous collection of urine and faeces from dose application until termination. Metabolism cages were washed with equal amounts of methanol and deionised water (approximately 500 mL total volume).
- Collection of expired air: no
- Skin from the application site was excised
SAMPLE PREPARATION
- Storage procedure:
- Preparation details: cage wash, bandage rinse, soap rinse, water rinse, paper rinse, aluminium foil rinse, solubilised skin and urine were aliquoted directly. Carcasses were ground with a Hobart food cutter and homogenised. Faeces were homogenised with dry ice and a micromill. Paper, gauze squares, faeces, blood and carcass homogenates were combusted using a Harvey Oxidizer.
ANALYSIS
- Method type(s) for identification (Liquid scintillation counting): the scintillation cocktail used for directly aliquoted samples was Scint-A. Combusted samples were assayed and counted in Oxosol-14C. Combustion efficiencies were determined using 14C-benzoic acid standard. All counting was by a Beckman Model LS-3801 and efficiencies determined by external standardisation.
Results and discussion
- Signs and symptoms of toxicity:
- no effects
- Remarks:
- (see cross-reference to other study)
- Dermal irritation:
- no effects
- Remarks:
- (see cross-reference to other study)
- Total recovery:
- 10-hour exposure: total 14C recovery the 2, 4, and 10 hour time points ranged from 100.3 - 106.3% for the low dose level and 102.2% - 106.5% for the high dose level.
24-hour exposure: total 14C recovery mean values were 98.8% for the low dose level and 97.9% for the high dose level.
Percutaneous absorptionopen allclose all
- Dose:
- 1.0 mg/rat
- Parameter:
- percentage
- Absorption:
- 49.4 %
- Remarks on result:
- other: 10 hrs
- Dose:
- 1.0 mg/rat
- Parameter:
- percentage
- Absorption:
- 55.7 %
- Remarks on result:
- other: 24 hrs
- Dose:
- 10.0 mg/rat
- Parameter:
- percentage
- Absorption:
- 25.4 %
- Remarks on result:
- other: 10 hrs
- Dose:
- 10.0 mg/rat
- Parameter:
- percentage
- Absorption:
- 27.5 %
- Remarks on result:
- other: 24 hrs
Any other information on results incl. tables
The actual doses were 0.88 mg/rat and 8.3 mg/rat equivalent to 0.088 and 0.83 mg/sq.cm for the 1.0 and 10.0 mg/rat dose levels respectively.
Total 14C mean recoveries ranged from 98.8-106.3% for the low dose level, and 97.9-106.5% for the high dose level. After a 10-hour exposure period, the total amount absorbed (excreta, blood, carcass, washed skin) was 49.4% and 25.4% for the low and high dosage levels, respectively. After a 24-hour exposure period, the total amount absorbed (excreta, blood, carcass, and washed skin) was 55.7% for the low dose level and 27.5% for the high dose level. The extra 14-hour exposure period between 10 and 24 hours did not significantly increase the amount of absorption of CGA154281. The rate of absorption of 14C-CGA154281 is inversely related to the dosage level. For all dosage levels, 3-33% was excreted in either a 10 or 24 hour period. The main route of excretion was via the urine. For both dosage levels, excretion values progressively increased from two to twenty-four hours.
The % of dose absorbed, unabsorbed and remaining in the skin after a soap and water rinse in animals treated with14C- CGA154281 at 1.0 mg/rat to 10 cm2of skin.
|
2 hours |
4 hour |
10 hours |
24 hours |
Blood |
0.01 |
0.07 |
0.14 |
0.09 |
Carcass |
11.48 |
5.25 |
10.09 |
7.49 |
Urine |
0.69 |
1.31 |
16.95 |
31.71 |
Faeces |
0.00 |
0.00 |
0.07 |
2.24 |
|
12.18 |
6.63 |
27.25 |
41.53 |
Skin I |
27.59 |
21.60 |
22.14 |
14.18 |
Skin II |
0.00 |
0.00 |
0.00 |
0.00 |
Total skin |
27.59 |
21.60 |
22.14 |
14.18 |
Absorbed1 |
39.77 |
28.23 |
49.39 |
55.71 |
Bandage |
0.51 |
0.47 |
0.39 |
0.85 |
Foil rinse |
0.09 |
0.12 |
0.09 |
0.25 |
Paper rinse |
0.52 |
1.03 |
2.10 |
2.99 |
Paper |
0.03 |
0.03 |
0.15 |
0.07 |
Soap rinse |
57.38 |
61.42 |
43.16 |
32.39 |
Water rinse |
5.52 |
5.88 |
4.29 |
3.06 |
Gauze A |
1.81 |
1.91 |
1.33 |
0.90 |
Gauze B |
0.10 |
0.08 |
0.09 |
0.05 |
Cage wash |
0.52 |
1.10 |
1.19 |
2.49 |
Unabsorbed2 |
66.48 |
72.04 |
52.79 |
43.05 |
Total14C recovered |
106.25 |
100.27 |
102.18 |
98.76 |
1Summation of the blood, carcass, urine, faeces, skin I and skin II
2Summation of the bandage, foil rinse, paper rinse, paper, soap rinse, water rinse, gauze A, gauze B and cage wash
The % of dose absorbed, unabsorbed and remaining in the skin after a soap and water rinse in animals treated with14C- CGA154281 at 10.0 mg/rat to 10 cm2of skin.
|
2 hours |
4 hour |
10 hours |
24 hours |
Blood |
0.01 |
0.02 |
0.04 |
0.04 |
Carcass |
0.83 |
1.73 |
2.17 |
3.59 |
Urine |
0.74 |
0.94 |
4.53 |
10.17 |
Faeces |
0.00 |
0.00 |
0.01 |
0.48 |
|
1.58 |
2.69 |
6.75 |
14.28 |
Skin I |
11.09 |
16.22 |
16.55 |
11.15 |
Skin II |
4.63 |
4.82 |
2.13 |
2.08 |
Total skin |
15.72 |
21.04 |
18.68 |
13.23 |
Absorbed1 |
17.30 |
23.73 |
25.43 |
27.51 |
Bandage |
1.10 |
0.39 |
1.24 |
0.72 |
Foil rinse |
0.02 |
0.03 |
0.27 |
0.08 |
Paper rinse |
0.11 |
0.18 |
0.26 |
0.49 |
Paper |
0.01 |
0.01 |
0.01 |
0.02 |
Soap rinse |
80.16 |
75.46 |
69.11 |
63.80 |
Water rinse |
2.54 |
3.98 |
3.63 |
2.56 |
Gauze A |
2.60 |
2.22 |
1.71 |
1.88 |
Gauze B |
0.05 |
0.26 |
0.05 |
0.04 |
Cage wash |
0.10 |
0.20 |
0.45 |
0.82 |
Unabsorbed2 |
86.69 |
82.73 |
76.73 |
70.41 |
Total14C recovered |
103.99 |
106.46 |
102.16 |
97.92 |
1Summation of the blood, carcass, urine, faeces, skin I and skin II
2Summation of the bandage, foil rinse, paper rinse, paper, soap rinse, water rinse, gauze A, gauze B and cage wash
Applicant's summary and conclusion
- Conclusions:
- The rate of absorption of 14C-CGA154281 is inversely related to the dosage level. For all dosage levels, 3-33% was excreted in either a 10 or 24 hour period. The main route of excretion was via the urine.
- Executive summary:
A single dermal dose of 14C-CGA154281 was administered to two groups of 16 male Sprague Dawley CD BR rats, at dose levels of 1.0 or 10.0 mg/rat. Urine and faecal samples were collected. Four animals from each dose level were killed at 2, 4, 10 and 24 hours after application of the test material. After the appropriate exposure time, the test material was removed by washing.
Total 14C mean recoveries ranged from 98.8-106.3% for the low dose level, and 97.9-106.5% for the high dose level. After a 10-hour exposure period, the total amount absorbed (excreta, blood, carcass, washed skin) was 49.4% and 25.4% for the low and high dosage levels, respectively. After a 24-hour exposure period, the total amount absorbed (excreta, blood, carcass, and washed skin) was 55.7% for the low dose level and 27.5% for the high dose level. The extra 14-hour exposure period between 10 and 24 hours did not significantly increase the amount of absorption of CGA154281. The rate of absorption of 14C-CGA154281 is inversely related to the dosage level. For all dosage levels, 3-33% was excreted in either a 10 or 24 hour period. The main route of excretion was via the urine. For both dosage levels, excretion values progressively increased from two to twenty-four hours.
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