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EC number: 416-530-4 | CAS number: 178949-82-1
- 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
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Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 4 to 7 May 1995
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 995
- Report date:
- 1995
Materials and methods
- Objective of study:
- absorption
- distribution
- excretion
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 417 (Toxicokinetics)
- Deviations:
- yes
- Remarks:
- only one low dose used
- GLP compliance:
- yes
Test material
- Reference substance name:
- -
- EC Number:
- 416-530-4
- EC Name:
- -
- Cas Number:
- 178949-82-1
- Molecular formula:
- C10H13N2Na3O8
- IUPAC Name:
- trisodium 2-({2-[(1-carboxy-2-carboxylatoethyl)amino]ethyl}amino)butanedioate
- Details on test material:
- - Name of test material (as cited in study report): radiolabelled-trisodium EDDS
- Substance type: technical product
- Physical state: clear liquid
- Radiochemical purity (if radiolabelling): 98.7%
- Specific activity (if radiolabelling): 16.1 uCi/mg
- Locations of the label (if radiolabelling): 14C on succinate groups
- Expiration date of radiochemical substance (if radiolabelling): 9 September 1993
- Stability under test conditions: no data
- Storage condition of test material: at about 4oC
Constituent 1
- Radiolabelling:
- yes
Test animals
- Species:
- rat
- Strain:
- other: Crl: (WI)BR
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Canada, St-Constant, Quebec
- Age at study initiation: 6-8 weeks
- Weight at study initiation: males: 191-303 g; females 173-253 g
- Fasting period before study: no data
- Housing: glass metabolism cages
- Individual metabolism cages: yes
- Diet (e.g. ad libitum): conventional, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 50 +/- 20
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 4 May 1993 To: 7 May 1993
Administration / exposure
- Route of administration:
- dermal
- Vehicle:
- water
- Details on exposure:
- TEST SITE
- Area of exposure: 7.6 cm2
- % coverage: no data
- Type of wrap if used: glass chamber applied with Permabond 102 adhesive
- Time intervals for shavings or clipplings: before dosing
REMOVAL OF TEST SUBSTANCE
- Washing (if done): test site washed at study termination at 72 h, and included with the rinsings from the dermal chamber for counting of radioactivity
- Time after start of exposure: 72 h
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.2 mL aqueous solution
- concentration (if solution): males, 4.14 mg/kg bw (66.7 uCi/kg bw); females, 5.12 mg/kg bw (84.0 uCi/kg bw )
VEHICLE
- Justification for use and choice of vehicle (if other than water): water
- Amount(s) applied: 0.2 mL
USE OF RESTRAINERS FOR PREVENTING INGESTION: no - Duration and frequency of treatment / exposure:
- 72 h
Doses / concentrationsopen allclose all
- Dose / conc.:
- 4.14 mg/kg bw/day (nominal)
- Remarks:
- Males, 4.14 mg/kg bw (66.7 uCi/kg bw)
- Dose / conc.:
- 5.12 mg/kg bw/day (nominal)
- Remarks:
- females, 5.12 mg/kg bw (84.0 uCi/kg bw )
- No. of animals per sex per dose / concentration:
- 5/sex test group
1 male acted as a control - Control animals:
- yes, concurrent vehicle
- Positive control reference chemical:
- no
- Details on study design:
- - Dose selection rationale: selected to provide sufficient material to determine the distribution, elimination and mass balance of radioactivity
- Rationale for animal assignment (if not random): random - Details on dosing and sampling:
- PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, faeces, blood, plasma, cage washes, expired air, adipose tissue, brain, bone marrow, femur bone, gonads, heart, GI (combined stomach, large and small intestine), GI contents, kidneys, liver, lungs, muscle (right leg adductor), pancreas, spleen, carcass, skin from test site and three adjacent sites.
- Time and frequency of sampling: urine, faeces and cage washes were collected at 24, 48 and 72 h; expired air was trapped in potassium hydroxide and collected at 12, 24, 36, 48 and 72 h. Tissues and organs were sampled for radioactivity at study termination (72 h). - Statistics:
- Bartlett's test and t-tests were used to determine any gender differences in the recovery of radioactivity. A in-transformation on the percent of dose was used to correct the non homogeneity of the variances when appropriate. For the skin test site, adjacent skin and dermal cell rinse a one-way ANOVA was used to compare the gender effect. The parameters tested were: radioactivity recovered in the tissues, urine, faeces, expired air, skin dose site, adjacent skin, dermal cell rinse and total recovered radioactivity.
Results and discussion
- Preliminary studies:
- none
Main ADME resultsopen allclose all
- Type:
- absorption
- Results:
- After 72 h, 11.1% of applied dose was absorbed in males; 5% absorbed in females
- Type:
- distribution
- Results:
- the combined mean blood and tissue (including carcass) recovery was 2.34% in males and 1.45% in females
- Type:
- excretion
- Results:
- about 9% of the applied dose was excreted in males and about 4% in females during 72 h exposure
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- Only about 11% of the applied dose was absorbed in males and 5% in females during the 72 h exposure period.
The total recovery of radioactivity was 59.1% in males and 62.8% in females. This mainly represented unabsorbed material found at the skin treatment site (about 40% of applied dose) and dermal chamber washings (about 10%). - Details on distribution in tissues:
- Low amounts of radioactivity were detected in the organs and tissues examined, ranging from 0% to up to 1.2% in the male carcass. See table 1 for details.
- Details on excretion:
- Less than 9% of applied dose recovered in the excreta (urine, faeces, cage wash and expired air). See tables 1 and 2 for details.
Metabolite characterisation studies
- Metabolites identified:
- not measured
Any other information on results incl. tables
Table 1. Total recovery (mass balance) of radioactivity after dermal exposure of rats
Sample |
Males (% of dose) |
Females (% of dose) |
Skin test site |
38.5 ± 9.38 |
43.9 ± 11.4 |
Skin adjacent site |
0.908 ± 0.829 |
0.916 ± 1.117 |
Dermal cell rinse |
8.60 ± 3.36 |
12.8 ± 7.42 |
Urine |
2.26 ± 1.63 |
0.521 ± 0.578 |
Faeces |
4.90 ± 3.79 |
2.06 ± 2.69 |
Expired air |
0.643 ± 0.413 |
0.340 ± 0.186 |
Cage wash |
0.954 ± 0.879 |
0.805 ± 0.893 |
Blood |
0.003 ± 0.006 |
0.000 ± 0.000 |
Liver |
0.025 ± 0.021 |
0.023 ± 0.022 |
Kidneys |
0.012 ± 0.012 |
0.004 ± 0.003 |
Heart |
0.000 ± 0.000 |
0.001 ± 0.002 |
Lungs |
0.000 ± 0.000 |
0.007 ± 0.010 |
Pancreas |
0.002 ± 0.002 |
0.002 ± 0.001 |
Spleen |
0.000 ± 0.000 |
0.004 ± 0.005 |
Brain |
0.000 ± 0.000 |
0.000 ± 0.000 |
Testes/ovaries |
0.000 ± 0.001 |
0.001 ± 0.002 |
Muscle |
0.014 ± 0.031 |
0.000 ± 0.000 |
Epididymal fat |
0.014 ± 0.018 |
0.121 ± 0.156 |
Bone marrow |
0.000 ± 0.000 |
0.000 ± 0.000 |
Bone femur |
0.000 ± 0.000 |
0.001 ± 0.002 |
GI tract |
0.173 ± 0.297 |
0.184 ± 0.233 |
GI contents |
0.896 ± 1.38 |
0.314 ± 0.261 |
Carcass |
1.20 ± 0.914 |
0.794 ± 0.738 |
Total |
59.1 ± 8.03 |
62.8 ± 18.6 |
Table 2. Mean cumulative recovery of radioactivity in excreta after dermal exposure
Time (h) |
Males (% of dose) |
Females (% of dose) |
||||||||
|
Urine |
Faeces |
Expired air |
Cage wash |
Total |
Urine |
Faeces |
Expired air |
Cage wash |
Total |
0-12 |
a |
a |
0.086 ± 0.014 |
a |
0.086 ± 0.014 |
a |
a |
0.087 ± 0.035 |
a |
0.087 ± 0.035 |
0-24 |
1.51 ± 1.59 |
0.884 ± 1.18 |
0.145 ± 0.05 |
0.492 ± 0.627 |
3.03 ± 3.36 |
0.355 ± 0.26 |
0.168 ± 0.212 |
0.111 ± 0.043 |
0.032 ± 0.049 |
0.577 ± 0.438 |
0-36 |
1.51 ± 1.59 |
0.884 ± 1.18 |
0.251 ± 0.116 |
0.492 ± 0.627 |
3.14 ± 3.34 |
0.355 ± 0.26 |
0.168 ± 0.212 |
0.162 ± 0.079 |
0.032 ± 0.049 |
0.628 ± 0.470 |
0.45 |
1.74 ± 1.59 |
2.44 ± 1.79 |
0.437 ± 0.244 |
0.730 ± 0.722 |
5.35 ± 3.15 |
0.349 ± 0.322 |
0.998 ± 1.63 |
0.226 ± 0.152 |
0.627 ± 0.692 |
2.20 ± 2.66 |
0-72 |
2.26 ± 1.63 |
4.90 ± 3.79 |
0.643 ± 0.413 |
0.954 ± 0.879 |
8.76 ± 4.87 |
0.521 ± 0.578 |
2.06 ± 2.69 |
0.340 ± 0.186 |
0.805 ± 0.893 |
3.72 ± 4.28 |
a, no sample collected
Applicant's summary and conclusion
- Conclusions:
- In a GLP study, similar to OECD Guideline 417, only about 11% of the applied dermal dose of radiolabelled-trisodium EDDS was considered absorbed in males and 5% in females following a 72-h exposure period. Less than 9% was recovered in the excreta (urine, faeces, cage wash and expired air). Low amounts of radioactivity were detected in the organs and tissues examined, ranging from 0% to up to 1.2% in the male carcass.
- Executive summary:
In a GLP study conducted according to a protocol similar to OECD Guideline 417, the absorption, distribution and elimination of 14C-trisodium EDDS was determined in male and female Wistar rats.
The radiolabelled test substance was applied (in water) at 4-5 mg/kg bw in a glass chamber to the shaved skin of five rats of each sex for 72 h. Urine, faeces, cage washings and expired air were collected at intervals throughout the study period and the radioactive content was measured. At study termination, levels of radioactivity were determined in adipose tissue, brain, bone marrow, femur bone, gonads, heart, gastrointestinal tract, gastrointestinal contents, kidneys, liver, lungs, muscle, pancreas, spleen, carcass, skin from the treatment site and adjacent sites.
The total recovery of radioactivity from all sources was 59.1% in males and 62.8% in females. This mainly represented unabsorbed material found at the skin treatment site (about 40%) and in the dermal chamber washings (about 10%). Only about 11% of the applied dose was considered absorbed in males and 5% in females during the 72-h exposure period, with less than 9% recovered in the excreta (urine, faeces, cage wash and expired air). Low amounts of radioactivity were detected in the organs and tissues examined, ranging from 0% to up to 1.2% in the male carcass.
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