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EC number: 203-951-1 | CAS number: 112-25-4
- 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
Endpoint summary
Administrative data
Link to relevant study record(s)
- Endpoint:
- basic toxicokinetics
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1989
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: The study was conducted as per compliance to Good Laboratory Practices TSCA Standards; Federal Register 48(230): 5397-53944, November 29, 1983.
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
- Objective of study:
- other: pharmacokinetics
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EPA OPPTS 870.8320 (Oral/dermal pharmacokinetics)
- Principles of method if other than guideline:
- not applicable
- GLP compliance:
- yes
- Radiolabelling:
- yes
- Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Hazleton-Dutchland
- Age at study initiation: 9-10 weeks of age
- Weight at study initiation: 2-3 kg
- Fasting period before study: not specified
- Housing: individually housed in Roth-type metabolism cages
- Individual metabolism cages: yes
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): standard conditions
- Humidity (%): standard conditions
- Air changes (per hr): standard conditions
- Photoperiod (hrs dark / hrs light): 12-hour light/darkcycle - Route of administration:
- intravenous
- Vehicle:
- physiological saline
- Details on exposure:
- In the intravenous studies, EGHE and 14C-EGHE were diluted in 0.9% (w/v) NaCl in water. The dose solution was delivered gravimetrically to each animal in a study. In intravenous studies, the dose solution was delivered using a syringe with a sawed-off needle into an indwelling cannula over a period of 2 minutes. The dose volume was followed by the same volume of 0.9% NaCl to clear the cannula, then the cannula was plugged.
- Duration and frequency of treatment / exposure:
- single
- Remarks:
- Doses / Concentrations:
10 and 1 mg/kg - No. of animals per sex per dose / concentration:
- 6 animals
- Control animals:
- not specified
- Positive control reference chemical:
- not applicable
- Details on study design:
- - Dose selection rationale: based on acute and probe study
- Rationale for animal assignment: random - Details on dosing and sampling:
- PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, faeces, plasma, blood, cage washes
- Time and frequency of sampling: Urine was collected on dry ice in 6- to 12-hr intervals and feces in 24-hr intervals. Urine samples were assayed immediately for 14c and the remaining volumes were stored at approximately -80°C until chemical analysis was conducted by HPLC. Feces were frozen at approximately -20°C until analyzed. Expired 14CO2, was collected at 12-hour intervals and stored at approximately -20°C until analyzed for 14C
- Statistics:
- The pharmacokinetic description of the fate of absorbed l4C-EGHE w as derived using best-fit parameter estimates for the plasma. The parameters
estimated included: rate constant of absorption, ka; rate constant of elimination, ke; volume of distribution, Vd; half-lives (t1/2) of absorption and elimination and area under the plasma concentration (AUC) versus time. - Preliminary studies:
- not applicable
- Details on absorption:
- no data
- Details on distribution in tissues:
- no data
- Details on excretion:
- The disposition of radioactivity following 10 and 0.1 mg/kg doses of EGHE/14C-EGHE to male NZW rabbits was that the total recovery of dose in excreta fractions, carcass and the cage wash was approximately 95 to 100% in the two dose groups.
A majority of the dose was eliminated in the urine (approximately 80%) while less than 2% was eliminated in the feces (largely in the first day of exposure).
There were no marked difference in rates or extents of urinary elimination observed between the two dose groups. In general, most of the dose recovered in the urine was eliminated in the first 24 hours after dosing, after which little additional urinary elimination of the dose occurred. - Test no.:
- #1
- Toxicokinetic parameters:
- Cmax: (10 mg/kg): 42.491 µg/g
- Test no.:
- #1
- Toxicokinetic parameters:
- Tmax: (10 mg/kg): 0 minutes
- Test no.:
- #1
- Toxicokinetic parameters:
- half-life 1st: (10 mg/kg): Half-life of distribution: 40.232 min
- Test no.:
- #1
- Toxicokinetic parameters:
- AUC: (10 mg/kg): AUC(48): 3598.5 µg/g.min
- Test no.:
- #1
- Toxicokinetic parameters:
- AUC: (10 mg/kg): AUC(∞): 4241.3 µg/g.min
- Test no.:
- #1
- Toxicokinetic parameters:
- other: (10 mg/kg): Distribution rate constant k(d): 0.017229 min(-1)
- Test no.:
- #1
- Toxicokinetic parameters:
- other: (10 mg/kg): Elimination rate constant k(e): 0.00036001 min (-1)
- Test no.:
- #1
- Toxicokinetic parameters:
- other: (10 mg/kg): Apparent volume of distribution Vd: 32610 ml
- Test no.:
- #1
- Toxicokinetic parameters:
- other: (10 mg/kg): Systemic clearance Cl(tot): 11.74 ml/min
- Test no.:
- #1
- Toxicokinetic parameters:
- half-life 2nd: (10 mg/kg): Half-life of elimination: 1925.4 min
- Test no.:
- #2
- Toxicokinetic parameters:
- Cmax: (1.0 mg/kg): 5.0998 µg/g
- Test no.:
- #2
- Toxicokinetic parameters:
- Tmax: (1.0 mg/kg): 0 minutes
- Test no.:
- #2
- Toxicokinetic parameters:
- half-life 1st: (1.0 mg/kg): Half-life of distribution: 16.917 min
- Test no.:
- #2
- Toxicokinetic parameters:
- AUC: (1.0 mg/kg): AUC(48): 288.73 µg/g.min
- Test no.:
- #2
- Toxicokinetic parameters:
- AUC: (1.0 mg/kg): AUC(∞): 357.38 µg/g.min
- Test no.:
- #2
- Toxicokinetic parameters:
- other: (1.0 mg/kg): Distribution rate constant k(d): 0.040973 min(-1)
- Test no.:
- #2
- Toxicokinetic parameters:
- other: (1.0 mg/kg): Elimination rate constant k(e): 0.00029278 min (-1)
- Test no.:
- #2
- Toxicokinetic parameters:
- other: (1.0 mg/kg): Apparent volume of distribution Vd: 43640 ml
- Test no.:
- #2
- Toxicokinetic parameters:
- other: (1.0 mg/kg): Systemic clearance Cl(tot): 12.777 ml/min
- Test no.:
- #2
- Toxicokinetic parameters:
- half-life 2nd: (1.0 mg/kg): Half-life of elimination: 2367.5 min
- Metabolites identified:
- no
- Details on metabolites:
- 3-9 peaks were observed, none of which corresponded to EGHE. These peaks were probably considered metabolites of EGHE, of which at least three of which appear to be major urinary metabolites.
- Conclusions:
- Interpretation of results: low bioaccumulation potential based on study results
Under the conditions of the study, the results in rabbits indicate that while EGHE has a large potential for systemic absorption, it is rapidly and extensively eliminated from the plasma by metabolic conversion to multiple metabolite species. - Executive summary:
The absorption, distribution, metabolism and elimination of ethylene glycol monohexyl ether (EGHE) following single intravenous dose was investigated in rabbits. In New Zealand White rabbits, intravenous doses of 10 and 1 mg/kg EGHE given to male rabbits were metabolized rapidly, so that EGHE levels were less than 1% of the total plasma radioactivity by 1 hour post-dosing. About 80% of the radioactivity was recovered in the urine, with less than 2% in the feces. Because the rabbits were housed in open metabolism cages, the recoveries of radioactivity in CO2 and organic volatile fractions could not be assessed; however, over 90% of the dose was recovered in the intravenous studies. The results in rabbits indicate that, while EGHE has a large potential for systemic absorption, it is rapidly and extensively eliminated from the plasma by metabolic conversion to multiple metabolite species.
- Endpoint:
- dermal absorption in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1989
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: The study was conducted with compliance to Good Laboratory Practices TSCA Standards; Federal Register 48(230): 5397-53944, November 29, 1983.
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EPA OPP 85-3 (Dermal Penetration)
- Principles of method if other than guideline:
- not applicable
- GLP compliance:
- yes
- Radiolabelling:
- yes
- Remarks:
- C14- Labeled EGHE
- Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Hazleton-Dutchland, denver ,PA
- Age at study initiation: 9-10 weeks
- Weight at study initiation: 2 - 3 kgs
- Housing: Open rack-type metabolism cages
- Individual metabolism cages: yes
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum):Ad libitum
- Acclimation period:5 days
ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light):12 hour photoperiod - Type of coverage:
- occlusive
- Vehicle:
- unchanged (no vehicle)
- Duration of exposure:
- 48 hour experimental period
- Doses:
- Percutaneous Male-10mg/kg
Percutaneous Female-10mg/kg - No. of animals per group:
- 5 animals per group
- Control animals:
- no
- Details on study design:
- APPLICATION OF DOSE: 10mg/kg EGHE to male and female rabbits.
TEST SITE
- Preparation of test site: The dose material was applied to the skin using a syringe and needle
- Area of exposure: Occluded with polyethylene sheeting held in place woth waterproof surgical tape and covered with stretch adhesive bandage tape.
SITE PROTECTION / USE OF RESTRAINERS FOR PREVENTING INGESTION: yes:
SAMPLE COLLECTION
- Collection of blood: 1,2,4,8,12,24,30,36 and 48 hours
- Collection of urine and faeces: Done
- Details on in vitro test system (if applicable):
- not applicable
- Signs and symptoms of toxicity:
- not specified
- Dermal irritation:
- no effects
- Absorption in different matrices:
- Refer to attachment
- Total recovery:
- Refer to attachment
- Conversion factor human vs. animal skin:
- not applicable
- Conclusions:
- The results in rabbits indicates that EGHE (Ethylene glycol hexyl ether) has a large potential for systemic absorption, it is rapidly and extensively eliminated from the plasma by metabolic conversion to multiple metabolite species.
- Executive summary:
New Zealand White rabbits were used to access Skin Penetration and Pharmacokinetics of Ethylene Glycol Monohexyl Ether (EGHE). Intravenous doses of 10 and 1 mg/kg EGHE given to male rabbits were metabolized rapidly, so that EGHE levels were less than 1% of the total plasma radioactivity by 1 hour post-dosing. About 80% of the radioactivity was recovered in the urine, with less than 2% in the feces. Because the rabbits were housed in open metabolism cages, the recoveries of radioactivity in C02and organic volatile fractions could not be assessed; however, over 90% of the dose was recovered in the intravenous studies. After cutaneous dosing of 10 mg/kg EGHE to male and female rabbits, about 75% of the dose was recovered; the remainder of the dose may have been lost because the organic volatile fraction could not be collected. No sex differences in the disposition of EGHE were observed. EGHE penetrated the skin rapidly, and the radioactivity was widely distributed. Most of the radioactivity was eliminated in the urine (55-65%) with minimal recovery in feces. The cutaneous bioavailability, based on total radioactivity, was greater than 65%; however, EGHE was extensively metabolized so that it accounted for less than 10% of the total radioactivity by 1 hour post-dosing. In nearly all urine fractions no EGHE was detected, but up to nine metabolite peaks were found.
No marked accumulation of EGHE was observed in a variety of tissues and organs that were analyzed.
The results in and rabbits indicate that, while EGHE has a large potential for systemic absorption, it is rapidly and extensively eliminated from the plasma by metabolic conversion to multiple metabolite species.
- Endpoint:
- basic toxicokinetics
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1989
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: The study was conducted as per compliance to Good Laboratory Practices TSCA Standards; Federal Register 48(230): 5397-53944, November 29, 1983.
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
- Objective of study:
- other: pharmacokinetics
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EPA OPPTS 870.8320 (Oral/dermal pharmacokinetics)
- Principles of method if other than guideline:
- not applicable
- GLP compliance:
- yes
- Radiolabelling:
- yes
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Sprague Dawley, Inc.
- Age at study initiation: 11-12 weeks old
- Weight at study initiation: not specified
- Fasting period before study: not specified
- Housing: group housed during acclimation and individually housed in Roth-type metabolism cages
- Individual metabolism cages: yes
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): standard conditions
- Humidity (%): standard conditions
- Air changes (per hr): standard conditions
- Photoperiod (hrs dark / hrs light): 12-hour light/darkcycle - Route of administration:
- intravenous
- Vehicle:
- physiological saline
- Details on exposure:
- In the intravenous studies, EGHE and 14C-EGHE were diluted in 0.9% (w/v) NaCl in water. The dose solution was delivered gravimetrically to each animal in a study. In intravenous studies, the dose solution was delivered using a syringe with a sawed-off needle into an indwelling cannula over a period of 2 minutes. The dose volume was followed by the same volume of 0.9% NaCl to clear the cannula, then the cannula was plugged.
- Duration and frequency of treatment / exposure:
- single
- Remarks:
- Doses / Concentrations:
25 and 2.5 mg/kg - No. of animals per sex per dose / concentration:
- 4 animals
- Control animals:
- not specified
- Positive control reference chemical:
- not applicable
- Details on study design:
- - Dose selection rationale: based on acute study
- Rationale for animal assignment: random - Details on dosing and sampling:
- PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, faeces, plasma, blood, cage washes
- Time and frequency of sampling: Urine was collected on dry ice in 6- to 12-hr intervals and feces in 24-hr intervals. Urine samples were assayed immediately for 14c and the remaining volumes were stored at approximately -80°C until chemical analysis was conducted by HPLC. Feces were frozen at approximately -20°C until analyzed. Expired 14CO2, was collected at 12-hour intervals and stored at approximately -20°C until analyzed for 14C
- Statistics:
- The pharmacokinetic description of the fate of absorbed l4C-EGHE w as derived using best-fit parameter estimates for the plasma. The parameters
estimated included: rate constant of absorption, ka; rate constant of elimination, ke; volume of distribution, Vd; half-lives (t1/2) of absorption and elimination and area under the plasma concentration (AUC) versus time. - Preliminary studies:
- not applicable
- Details on absorption:
- no data
- Details on distribution in tissues:
- no data
- Details on excretion:
- A majority of the dose was eliminated in the urine (approximately 65 to 75%) while less than 10% was eliminated as CO2 and less than 5% was eliminated in the feces (largely in the first day of exposure in C02 and feces fractions).
There was no marked difference in rates or extents of urinary elimination between the two dose groups. In general, most of the dose recovered in the urine was eliminated in the first 6 hours after dosing. - Test no.:
- #1
- Toxicokinetic parameters:
- Cmax: (25 mg/kg): 129.25 µg/g
- Test no.:
- #1
- Toxicokinetic parameters:
- Tmax: (25 mg/kg): 0 minutes
- Test no.:
- #1
- Toxicokinetic parameters:
- half-life 1st: (25 mg/kg): Half-life of distribution: 15.213 min
- Test no.:
- #1
- Toxicokinetic parameters:
- AUC: (25 mg/kg): AUC(48): 8153.2 µg/g.min
- Test no.:
- #1
- Toxicokinetic parameters:
- AUC: (25 mg/kg): AUC(∞): 8153.2 µg/g.min
- Test no.:
- #1
- Toxicokinetic parameters:
- other: (25 mg/kg): Distribution rate constant k(d): 0.04562 min(-1)
- Test no.:
- #1
- Toxicokinetic parameters:
- other: (25 mg/kg): Elimination rate constant k(e): 0.00080246 min (-1)
- Test no.:
- #1
- Toxicokinetic parameters:
- other: (25 mg/kg): Apparent volume of distribution Vd: 1013 ml
- Test no.:
- #1
- Toxicokinetic parameters:
- other: (25 mg/kg): Systemic clearance Cl(tot): 0.8129 ml/min
- Test no.:
- #1
- Toxicokinetic parameters:
- half-life 2nd: (25 mg/kg): Half-life of elimination: 863.78 min
- Test no.:
- #2
- Toxicokinetic parameters:
- Cmax: (2.5 mg/kg): 9.1632 µg/g
- Test no.:
- #2
- Toxicokinetic parameters:
- Tmax: (2.5 mg/kg): 0 minutes
- Test no.:
- #2
- Toxicokinetic parameters:
- half-life 1st: (2.5 mg/kg): Half-life of distribution: 17.301 min
- Test no.:
- #2
- Toxicokinetic parameters:
- AUC: (2.5 mg/kg): AUC(48): 619.25 µg/g.min
- Test no.:
- #2
- Toxicokinetic parameters:
- AUC: (2.5 mg/kg): AUC(∞): 619.25 µg/g.min
- Test no.:
- #2
- Toxicokinetic parameters:
- other: (2.5 mg/kg): Distribution rate constant k(d): 0.040065 min(-1)
- Test no.:
- #2
- Toxicokinetic parameters:
- other: (2.5 mg/kg): Elimination rate constant k(e): 0.00067483 min (-1)
- Test no.:
- #2
- Toxicokinetic parameters:
- other: (2.5 mg/kg): Apparent volume of distribution Vd: 1507 ml
- Test no.:
- #2
- Toxicokinetic parameters:
- other: (2.5 mg/kg): Systemic clearance Cl(tot): 1.017 ml/min
- Test no.:
- #2
- Toxicokinetic parameters:
- half-life 2nd: (2.5 mg/kg): Half-life of elimination: 1027.1 min
- Metabolites identified:
- no
- Details on metabolites:
- 2-7 peaks were observed, none of which corresponded to EGHE and these peaks were considered to probably be metabolites of EGHE, of which at least three of which appear to be major urinary metabolites.
- Conclusions:
- Interpretation of results: low bioaccumulation potential based on study results
The results in rats indicate that while EGHE has a large potential for systemic absorption, it is rapidly and extensively eliminated from the plasma by metabolic conversion to multiple metabolite species. - Executive summary:
The absorption, distribution, metabolism and elimination of ethylene glycol monohexyl ether (EGHE) following single intravenous doses were investigated in rats. In male Fischer 344 rats, intravenous doses of 25 and 2.5 mg/kg EGHE were metabolized rapidly, such that EGHE was less than 1% of the total radioactivity in the plasma by 8 hours post-dosing. The remaining plasma radioactivity was eliminated mostly in the urine (~65-75%) with minimal amounts of radioactivity recovered in feces or CO2 and organic volatile fractions. The results in rats indicate that while EGHE has a large potential for systemic absorption, it is rapidly and extensively eliminated from the plasma by metabolic conversion to multiple metabolite species.
- Endpoint:
- dermal absorption in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1989
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: The study was conducted with compliance to Good Laboratory Practices TSCA Standards; Federal Register 48(230): 5397-53944, November 29, 1983.
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EPA OPP 85-3 (Dermal Penetration)
- Principles of method if other than guideline:
- not applicable
- GLP compliance:
- yes
- Radiolabelling:
- yes
- Remarks:
- C14- Labeled EGHE
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Sprague Dawley, Inc.
- Age at study initiation: 11-12 week
- Housing: Roth-type metabolism cages
- Individual metabolism cages: yes
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period:5 days
ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light):12 hour photoperiod - Type of coverage:
- occlusive
- Vehicle:
- unchanged (no vehicle)
- Duration of exposure:
- 48 hour experimental period
- Doses:
- 25 mg/kg EGHE Percutaneous- Male
25 mg/kg EGHE Percutanesous- Female - No. of animals per group:
- 5 animals per group
- Control animals:
- no
- Details on study design:
- APPLICATION OF DOSE: 25 mg/kg EGHE to male and female rats
TEST SITE
- Preparation of test site: The dose material was applied to the skin using a syringe and needle
- Area of exposure: Occluded with polyethylene sheeting held in place woth waterproof surgical tape and covered with stretch adhesive bandage tape.
SITE PROTECTION / USE OF RESTRAINERS FOR PREVENTING INGESTION: yes:
SAMPLE COLLECTION
- Collection of blood: 1,2,4,8,12,24,30,36 and 48 hours
- Collection of urine and faeces: Done
- Details on in vitro test system (if applicable):
- not applicable
- Signs and symptoms of toxicity:
- not specified
- Dermal irritation:
- no effects
- Absorption in different matrices:
- Refer to attachment
- Total recovery:
- Refer to attachment
- Conversion factor human vs. animal skin:
- no data
- Conclusions:
- The results in rats indicates that EGHE (Ethylene glycol hexyl etherP) was extensively metabolized, so that it accounted for only 5-50% of the total plasma radioactivity.
- Executive summary:
Fischer 344 rats were used to access Skin Penetration and Pharmacokinetics of Ethylene Glycol Monohexyl Ether (EGHE). Intravenous doses of 25 and 2.5 mg/kg of EGHE given to the animals and were metabolized rapidly, such that EGHE was less than 1 % of the total radioactivity in the plasma by 8 hour post dosing. The remaining plasma radioactivity was eliminated mostly in the urine (nearly 65 -75%) with minimal amounts of radioactivity recovered in feces or CO2 and organic volatile fractions. After cutaneous dosing of 25 mg/kg EGHE to male and female rats, over 95% of the dose was recovered and no sex differece in EGHE disposition was observed. EGHE penetrated the sin rapidly and was widely distribute. In contrast to the intravenous route, less radioactivity was recovered in the urine (nearly 20 -30%), but significant amounts were found in feces and the organic volatile fraction (over 20 and 10%, respectively).
The cutaneous bioavailability was greater than 75% in rats when total radioactivity was measured; however, EGHE was extensively metabolized, so that it accounted for only 5 -50% of the total plasma radioactivity. EGHE was not found in urine fractions, but up to 7 urinary metabolite peaks were observed. There was no marked accumulation of radioactivity in liver, kidney, lund or a variety of other tissues and organs that were analyzed.
Referenceopen allclose all
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Description of key information
Short description of key information on bioaccumulation potential result:
The pharmacokinetics of Ethylene Glycol Hexyl Ether (EGHE) folllowing a single intravenous exposure to Fischer 344 rats and New Zealand rabbits was evaluated
Short description of key information on absorption rate:
The skin penetration and pharmacokinetics of ethylene glycol hexyl ether (EGHE) folllowing a single cutaneous exposure to Fischer 344 rats and New Zealand rabbits was evaluated
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
- Absorption rate - oral (%):
- 100
- Absorption rate - dermal (%):
- 75
- Absorption rate - inhalation (%):
- 100
Additional information
Several pharmacokinetics studies and skin penetration studies have been conducted with Ethylene Glycol Hexyl Ether (EGHE) in rats and rabbits.The results in both species indicate that, while EGHE has a large potential for systemic absorption, it is rapidly and extensively eliminated from the plasma by metabolic conversion to multiple metabolite species. After cutaneous dosing of EGHE to rats and rabbits, EGHE penetrated the skin rapidly and was widely distributed. The cutaneous bioavailability was greater than 75% in rats and greater than 65% in rabbits. However, EGHE was extensively metabolized. There was no marked accumulation of EGHE in liver, kidney, lung or a variety of other tissues and organs that were analyzed.
Discussion on bioaccumulation potential result:
The absorption, distribution, metabolism and elimination of ethylene glycol monohexyl ether (EGHE) following single intravenous dose was investigated in rats and rabbits. In male Fischer 344 rats, intravenous doses of 25 and 2.5 mg/kg EGHE were metabolized rapidly, such that EGHE was less than 1% of the total radioactivity in the plasma by 8 hours post-dosing. The remaining plasma radioactivity was eliminated mostly in the urine (~65-75%) with minimal amounts of radioactivity recovered in feces or CO2 and organic volatile fractions. In New Zealand White rabbits, similar results were obtained. Intravenous doses of 10 and 1 mg/kg EGHE given to male rabbits were metabolized rapidly, so that EGHE levels were less than 1% of the total plasma radioactivity by 1 hour post-dosing. About 80% of the radioactivity was recovered in the urine, with less than 2% in the feces. Because the rabbits were housed in open metabolism cages, the recoveries of radioactivity in C02 and organic volatile fractions could not be assessed; however, over 90% of the dose was recovered in the intravenous studies. The results in rats and rabbits indicate that, while EGHE has a large potential for systemic absorption, it is rapidly and extensively eliminated from the plasma by metabolic conversion to multiple metabolite species.
Discussion on absorption rate:
The absorption, distribution, metabolism and elimination of ethylene glycol monohexyl ether (EGHE) following single cutaneous dose were investigated in rats and rabbits. After cutaneous dosing of 25 mg/kg EGHE to male and female rats, over 95% of the dose was
recovered and no sex difference in EGHE disposition was observed. EGHE penetrated the skin rapidly and was widely distributed. In contrast to the intravenous route, less radioactivity was recovered in the urine (~20-30%), but significant amounts were found in feces and the organic volatile fraction (over 20 and 10%, respectively). The cutaneous bioavailability was greater than 75% in rats when total radioactivity was measured; however, EGHE was extensively metabolized, so that it accounted for only 5-50% of the total plasma radioactivity. EGHE was not found in urine fractions, but up to 7 urinary metabolite peaks were observed. There was no marked accumulation of radioactivity in liver, kidney, lung or a variety of other tissues and organs that were analyzed.
After cutaneous dosing of 10 mg/kg EGHE to male and female rabbits, about 75% of the dose was recovered; the remainder of the dose may have been lost because the organic volatile fraction could not be collected. No sex differences in the disposition of EGHE were observed. EGHE penetrated the skin rapidly, and the radioactivity was widely distributed. Most of the radioactivity was eliminated in the urine (55-65%) with minimal recovery in feces. The cutaneous bioavailability, based on total radioactivity, was greater than 65%;
However, EGHE was extensively metabolized so that it accounted for less than 10% of the total radioactivity by 1 hour post-dosing. In nearly all urine fractions no EGHE was detected, but up to nine metabolite peaks were found. No marked accumulation of EGHE was observed in a variety of tissues and organs that were analyzed.
The results in rats and rabbits indicate that, while EGHE has a large potential for systemic absorption, it is rapidly and extensively eliminated from the plasma by metabolic conversion to multiple metabolite species.
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