Fatty acids, C16-18 and C18-unsatd., esters with propylene glycol

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

bioaccumulation in aquatic species, other

Type of information:

other: Review article

Adequacy of study:

supporting study

Study period:

1997

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Toxicological profile (Review article), published by the Agency for Toxic Substances and Disease Registry, Atlanta GA, USA.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Toxicological profile, published by the Agency for Toxic Substances and Disease Registry, Atlanta GA, USA. Toxicological profiles are a unique compilation of toxicological information on a given hazardous substance. The profiles reflect a comprehensive and extensive evaluation, summary, and interpretation
of available toxicologic and epidemiologic information on a substance.

GLP compliance:

no

Test organisms (species):

other: not applicable

Metabolism

Commercially available propylene glycol is usually a mixture of D-and L-isomers. The major route of metabolism for propylene glycol is via alcohol dehydrogenase to lactaldehyde, then to lactate, via aldehyde dehydrogenase, and on to glucose through gluconeogenic pathways (as summarized in Christopher et al. 1990; Huff 1961; Miller and Bazzano 1965; Morshed et al. 1989, 1991; Ruddick 1972). Conversion to methylglyoxal is an alternate route via alcohol dehydrogenase, ending in metabolism to D-lactate through glyoxalase.

Excretion from oral exposure

The pharmacokinetic properties of propylene glycol are not completely understood, but absorption from the gastrointestinal tract is fairly rapid. The maximum plasma concentration of propylene glycol in humans is reached within 1 hour after oral exposure, while the elimination half-life is about, 4 hours. The total body clearance is about 0.1 L/kg/hour and seems to be serum-concentration dependent (Yu et al. 1985). Dose-dependent elimination is seen in rats, with saturation of the pathways at doses above 5,880 mg/kg (Morshed et al. 1988). An apparent maximum elimination rate of 8.3 mmol/kg/hour (630 mg/kg/hour) was observed.

 

References

Christopher MM, Perman V, White JG, et al. 1989. Propylene glycol-induced Heinz body formation and D-lactic acidosis in cats. Prog Clin Biol Res 319:69-92.

Huff E. 1961. Metabolism of 1,2-propanediol. Biochim Biophys Acta 48:506-517.

Miller ON, Bazzano G. 1965. Propanediol metabolism and its relation to lactic acid metabolism. Ann NY Acad Sci 119:959-973.

Morshed KM, Nagpaul JP, Majumdar S, et al. 1988. Kinetics of propylene glycol elimination and metabolism in rat. Biochem Med Metab Biol 39(1):90-97.

Morshed KM, Nagpaul JP, Majumdar S, et al. 1989. Kinetics of oral propylene glycol-induced acute hyperlactatemia. Biochem Med Metab Biol 42(2):87-94.

Morshed KM, Helgoualch AL, Nagpaul JP, et al. 1991. The role of propylene glycol metabolism in lactatemia in the rabbit. Biochemical Medicine and Metabolic Biology 46:145-151.

Ruddick JA. 1972. Toxicology, metabolism, and biochemistry of 1,2-propanediol. Toxicol Appl Pharmacol 21(1):102-111.

Yu DK, Elmquist WF, Sawchuk RJ. 1985.Pharmacokinetics of propylene glycol in humans during multiple dosing regimens.J Pharm Sci 74(8):876-879.

Reference 2

Endpoint:

bioaccumulation in aquatic species, other

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Toxicological profile (Review article), published by the Agency for Toxic Substances and Disease Registry, Atlanta GA, USA.

Justification for type of information:

Please refer section 13 for read across justification.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Toxicological profile, published by the Agency for Toxic Substances and Disease Registry, Atlanta GA, USA. Toxicological profiles are a unique compilation of toxicological information on a given hazardous substance. The profiles reflect a comprehensive and extensive evaluation, summary, and interpretation of available toxicologic and epidemiologic information on a substance.

GLP compliance:

no

Test organisms (species):

other: not applicable

Route of exposure:

other: not applicable

Ethylene glycol is quickly and extensively absorbed through the gastrointestinal tract of many species, but dermal absorption is slow in rodents and is expected to be slow in humans. Limited information is available on absorption of inhaled ethylene glycol, but the existing toxicity studies suggest absorption via the respiratory tract by both humans and rodents. Following absorption, ethylene glycol is distributed in aqueous compartments throughout the body. Ethylene glycol is converted to glycolaldehyde by nicotinamide adenine dinucleotide (NAD)-dependent alcohol dehydrogenase. Subsequent reduction of NAD results in the formation of lactic acid from pyruvate. Glycolaldehyde has a brief half-life and is rapidly converted to glycolic acid (and to a lesser extent glyoxal) by aldehyde dehydrogenase and aldehyde oxidase, respectively. Glycolic acid is oxidized to glyoxylic acid by glycolic acid oxidase or lactic dehydrogenase. Glyoxylic acid can be metabolized to formate, glycine, or malate, all of which may be further broken down to generate respiratory CO2, or to oxalic acid, which is excreted in the urine. In excess, oxalic acid can form calcium oxalate crystals. Rate-limiting steps in the metabolism of ethylene glycol include the initial formation of glycolaldehyde and the conversion of glycolic acid to glyoxylic acid, both of which are saturable processes. The half-life for elimination in humans has been estimated to be in the range of 2.5 - 8.4 hours.

Reference 3

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1999

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

The activity of carboxylesterase (CaE), a class of nonspecific serine hydrolases, was evaluated in vitro in tissues and microsomes of rainbow trout. In the assays the formation of 4-nitrophenol from 4-nitrophenyl acetate was measured spectrophotometrically.

GLP compliance:

no

Test organisms (species):

Oncorhynchus mykiss (previous name: Salmo gairdneri)

Details on test organisms:

TEST ORGANISM
- Common name: rainbow trout
- Source: Trouts were obtained as eyed embryos from Mt. Lassen Trout Farms, Mt. Lassen CA, USA
- Age at study initiation: < 1 year
- Length at study initiation (lenght definition, mean, range and SD):
- Weight at study initiation: 1.64 ± 0.07 g wet weight
- Weight at termination (mean and range, SD):
- Method of holding: Trout were held in flow-through aerated raceways at 12 ± 1 °C. The laboratory water was softened Lake Huron water that had been sand-filtered, pH adjusted with CO 2, carbon-filtered, and ultraviolet irradiated. Laboratory water was monitored weekly for pH, alkalinity, conductivity, and hardness; and quarterly for selected inorganics, pesticides, and poly-chlorinated biphenyls. Typical water quality values were pH of 7.5, alkalinity of 43 mg/L, hardness of 70 mg/L (as CaCO3 ), and conductivity of 140 mhos/cm. Fish were killed by a blow to the head and placed immediately on ice before tissue preparation.

Route of exposure:

other: In vitro exposure

Test type:

other: In vitro study

Water / sediment media type:

natural water: freshwater

The results of this study demonstrated that rainbow trout had high esterase activity over a broad range of temperatures, that carboxylesterase (CaE) activity significantly increased between the yolk-sac and juvenile life stages, and that variation between the CaE activity in trout and three other families of freshwater fish was limited.

Reference 4

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1990

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Acceptable, well documented publication which meets basic scientific principles.

Principles of method if other than guideline:

28-days uptake/4-days depuration study with Lepomis macrochirus under flow-through conditions.

GLP compliance:

no

Radiolabelling:

yes

Details on sampling:

- Sampling intervals/frequency for test organisms: Fish were sampled at 0.5, 1, 2, 4, 8, 14, 21 and 28 days during the exposure phase (5 fish per time point) and at 1, 2 and 4 days during the clearance phase (5 fish per time point).
- Sampling intervals/frequency for test medium samples: Water samples were taken daily. For analysis of parent compound and metabolites water samples from exposure aquarium were analysed at least once a week.
- Sample storage conditions before analysis: immediate analysis
- Details on sampling and analysis of test organisms and test media samples: Water samples were analysed using Liquid Scintillation (LS) counting method. Fish tissue samples were analyzed for radioactivity after combustion.

Vehicle:

yes

Details on preparation of test solutions, spiked fish food or sediment:

PREPARATION AND APPLICATION OF TEST SOLUTION
- Chemical name of vehicle: acetone
- Concentration of vehicle in test medium: 0.095 mL/L in the vehicle control

Test organisms (species):

Lepomis macrochirus

Details on test organisms:

TEST ORGANISM
- Common name: bluegill
- Source: Fish were purchased from Osage Catfisheries of Osage Beach MO, USA.
- Length at study initiation: 3.0 - 4.5 cm
- Weight at study initiation: 0.5 - 0.7 g

ACCLIMATION
- Acclimation period: > 21 days
- Type and amount of food: synthetic diet
- Feeding frequency: ad libitum

Route of exposure:

aqueous

Test type:

flow-through

Water / sediment media type:

natural water: freshwater

Total exposure / uptake duration:

28 d

Total depuration duration:

4 d

Hardness:

73 - 76 mg/L CaCO3

Test temperature:

16.3 - 17.9 °C

pH:

7.7 - 8.1

Dissolved oxygen:

8.1 - 9.6 mg/L

Details on test conditions:

TEST SYSTEM
- Test vessel: aquarium
- Type: covered with plexiglas lids
- Material, size: glass, 40 L
- Aeration: Aquaria were equipped with magnetic stirring bars.
- Type of flow-through: A three-way valve was located between the peristaltic pump and the mixing chambers so that the flow could be measured daily and adjusted.
- Renewal rate of test solution : 6 volume changes every 24 h
- No. of organisms per vessel: 85
- No. of vessels per concentration (replicates): 1 for exposure, 1 for depuration
- No. of vessels per control / vehicle control (replicates): 1

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: Dilution water used was from the upper Saginaw Bay of Lake Huron and was sand filtered, pH adjusted with CO2 to pH 8, carbon filtered and UV-radiated before use.
- Alkalinity: 46 - 52 mg/L as CaCO3
- Conductance: 140 - 150 µmhos/cm
- Intervals of water quality measurement: Temperature, pH and oxygen were measured periodically.

Nominal and measured concentrations:

Nominal: 0 (vehicle control), 0.33 µg/L
Measured: < LOD, 0.29 µg/L (average)

Reference substance (positive control):

no

Details on estimation of bioconcentration:

BASIS FOR CALCULATION OF BCF
- Estimation: Two compartment model is used to describe the uptake and elimination of xenobiotics by fish.

Type:

BCF

Value:

< 17 dimensionless

Basis:

not specified

Remarks on result:

other: Conc.in environment / dose:0.29 µg/L (measured average)

Metabolites:

Haloxyfop, polar metabolites 1 and 2.

Bluegill exposed to 14C haloxyfop-methyl for 28 days were found to rapidly absorb the ester from water which was then biotransformed at an extremely fast rate within the fish such that essentially no haloxyfop-methyl was detected in the fish. The estimated bioconcentration factor for the haloxyfop-methyl in whole fish was < 17, based upon the detection limit for ester in fish and the average concentration of haloxyfop-methyl in exposure water. The total 14C residue level within whole fish averaged about 0.27 µg/g equivalents over the course of the uptake phase. The principal component of the 14C residue was haloxyfop, which accounted for an average of about 60% of the radioactivity. Two other polar metabolites were detected in the fish which accounted for an average of about 14% of the radioactivity and an average of about 25% of the radioactivity. Once the fish were transferred to clean water, all metabolites cleared quickly with similar clearance rates. A simulation model estimated the uptake rate constant of haloxyfop-methyl from water to be about 720 mL/g*day. The rate constants for biotransformation of haloxyfop-methyl and the clearance of metabolites formed were estimated to be 200/day (DT50 = 5 min) and 0.82/day (DT50 = 0.8 days), respectively. The high rate of biotransformation of the parent compound within the fish demonstrates the importance of basing the bioconcentration factor upon the actual concentration of parent material within the organisms rather than the total radioactive residue levels for radiolabeled bioconcentration studies.

Reference 5

Endpoint:

bioaccumulation in aquatic species, other

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

June 2014

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification

Remarks:

Validated QSAR model. Calculation for the main component 2-[(Z)-octadec-9-enoyl]oxypropyl (Z)-octadec-9-enoate of the test substance, however the component is outside of the domain of the training set (log Kow of the training set: 0.31-8.70; log Kow of the component: 16.11). Nevertheless, the value of the prediction will be used for risk assessment purposes, since a) there is currently no universally accepted definition of model domain, and b) since further measurements/testing would not result in additional knowledge for this substance.

Justification for type of information:

QSAR prediction

Principles of method if other than guideline:

Calculation based on BCFBAF v3.01, Estimation Programs Interface Suite™ for Microsoft® Windows v 4.11. US EPA, United States Environmental Protection Agency, Washington, DC, USA.

GLP compliance:

no

Test organisms (species):

other: Fish

Route of exposure:

aqueous

Test type:

other: calculation

Water / sediment media type:

natural water: freshwater

Details on estimation of bioconcentration:

BASIS FOR CALCULATION OF BCF
- Estimation software: BCFBAF v3.01
- Result based on calculated log Pow of: 16.11 (estimated, KOWWIN v.1.68)

Type:

BAF

Value:

1.231 L/kg

Basis:

whole body w.w.

Remarks on result:

other: Arnot Gobas (including biotransformation rate estimates, upper trophic)

Key result

Type:

BCF

Value:

0.893 L/kg

Basis:

whole body w.w.

Remarks on result:

other: Arnot Gobas (including biotransformation rate estimates, upper trophic)

Estimated Log BCF (mid trophic)  = -0.031 (BCF = 0.9315 L/kg wet-wt)

Estimated Log BAF (mid trophic)  = -0.022 (BAF = 0.9505 L/kg wet-wt)

Estimated Log BCF (lower trophic) = -0.027 (BCF = 0.9402 L/kg wet-wt)

Estimated Log BAF (lower trophic) = -0.021 (BAF = 0.9527 L/kg wet-wt)

 

Arnot-Gobas BCF & BAF Methods (including biotransformation rate estimates):

Estimated Log BCF (upper trophic) = -0.049 (BCF = 0.893 L/kg wet-wt)

Estimated Log BAF (upper trophic) = -0.033 (BAF = 0.9276 L/kg wet-wt)

 

Biotransformation Rate Constant:

 kM (Rate Constant): 0.006176 /day (10 gram fish)

 kM (Rate Constant): 0.003473 /day (100 gram fish)

 kM (Rate Constant): 0.001953 /day (1 kg fish)

 kM (Rate Constant): 0.001098 /day (10 kg fish)

 

Reference 6

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Acceptable, well documented publication which meets basic scientific principles.

Qualifier:

no guideline followed

Principles of method if other than guideline:

In vitro enzyme study with liver microsomal and cytosolic fractions from different fish species recommended as test species in OECD guidelines.

GLP compliance:

no

Test organisms (species):

other: Poecilia reticulata, Cyprinus carpio, Danio rerio, Leuciscus idus, Salmo gairdneri

Details on test organisms:

TEST ORGANISM
- Common name: Guppy, common carp, zebra fish, golden orfe, rainbow trout
- Source: Guppy, common carp and zebra fish were purchased from Euraquarium, Bologna, Italy. Rainbow trout was kindly supplied by Istituto Ittiogenico, Rome, Italy.
- Length at study initiation: see Tab. 1
- Weight at study initiation: see Tab. 1
- Method of breeding: The guppy stocks were made up of adult females only, whereas all other fish stocks included individuals of both sexes. Fish sizes and rearing conditions were chosen to meet EEC test guidelines as closely as possible.

ACCLIMATION
- Acclimation period: Fish were acclimatised for at least one week.
- Type and amount of food: Fish were fed a semisynthetic diet purchased from Piccioni, Brescia, Italy.
- Health during acclimation (any mortality observed): Less than 2% mortality per week was observed in all the stocks used.

Route of exposure:

other: not applicable, in vitro study

Test type:

other: in vitro

Water / sediment media type:

natural water: freshwater

The metabolic efficiency of the liver in the enzymatic hydrolysis of exogenous substrates is dependent on both the substrate type and the fish species. Indeed, the fish studied metabolise much more readily phenyl acetate, the typical substrate of A-esterases, and the phosphate monoester, than the B-esterase substrates. The inter-species differences in activities (referred to unit body weight) vary within a factor of 7 – 17 for esterases (with p-nitrophenyl phosphate, phenyl acetate or ethyl-butyrate as substrate), while reaching a factor of variation of even 60 for acetanilide amidase.

In line with previous evidence on hepatic mono-oxygenase and glutathione S-transferases, guppy is the most active fish species, also with reference to non-specific hydrolases. At variance with results on the other enzyme families, carp also is endowed with the highest levels of hydrolases.

Reference 7

Endpoint:

bioaccumulation in aquatic species, other

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

March 2021

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Remarks:

Validated QSAR model. Calculation for the main component 2-[(Z)-octadec-9-enoyl]oxypropyl (Z)-octadec-9-enoate of the test substance is inside of the domain of the training set (log Kow of the training set: 0.31-8.70; log Kow of the component: 8.47).

Justification for type of information:

QSAR prediction

Principles of method if other than guideline:

Calculation based on BCFBAF v3.01, Estimation Programs Interface Suite™ for Microsoft® Windows v 4.11. US EPA, United States Environmental Protection Agency, Washington, DC, USA.

GLP compliance:

no

Test organisms (species):

other: Fish

Route of exposure:

aqueous

Test type:

other: calculation

Water / sediment media type:

natural water: freshwater

Details on estimation of bioconcentration:

BASIS FOR CALCULATION OF BCF
- Estimation software: BCFBAF v3.01
- Result based on calculated log Pow of: 8.47 (estimated, KOWWIN v.1.68)

Key result

Type:

BCF

Value:

641.5 L/kg

Basis:

other: wet-wt

Bioaccumulation Estimates (BCFBAF v3.01):

  Log BCF from regression-based method = 2.807 (BCF = 641.5 L/kg wet-wt)

  Log Biotransformation Half-life (HL) = -0.2972 days (HL = 0.5044 days)

  Log BCF Arnot-Gobas method (upper trophic) = 0.627 (BCF = 4.237)

  Log BAF Arnot-Gobas method (upper trophic) = 0.769 (BAF = 5.876)

 

  log Kow used: 8.47 (user entered)

Conclusions:

The BCF was determined to be 641.5 L/kg wet-wt

Reference 8

Endpoint:

bioaccumulation in aquatic species, other

Type of information:

read-across based on grouping of substances (category approach)

Remarks:

Reviewed article

Adequacy of study:

supporting study

Study period:

1997

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Toxicological profile (Review article), published by the Agency for Toxic Substances and Disease Registry, Atlanta GA, USA.

Justification for type of information:

Please refer section 13 for read across justification.

Reason / purpose for cross-reference:

read-across source

Qualifier:

no guideline followed

Principles of method if other than guideline:

Toxicological profile, published by the Agency for Toxic Substances and Disease Registry, Atlanta GA, USA. Toxicological profiles are a unique compilation of toxicological information on a given hazardous substance. The profiles reflect a comprehensive and extensive evaluation, summary, and interpretation
of available toxicologic and epidemiologic information on a substance.

GLP compliance:

no

Test organisms (species):

other: not applicable

Metabolism

Commercially available propylene glycol is usually a mixture of D-and L-isomers. The major route of metabolism for propylene glycol is via alcohol dehydrogenase to lactaldehyde, then to lactate, via aldehyde dehydrogenase, and on to glucose through gluconeogenic pathways (as summarized in Christopher et al. 1990; Huff 1961; Miller and Bazzano 1965; Morshed et al. 1989, 1991; Ruddick 1972). Conversion to methylglyoxal is an alternate route via alcohol dehydrogenase, ending in metabolism to D-lactate through glyoxalase.

Excretion from oral exposure

The pharmacokinetic properties of propylene glycol are not completely understood, but absorption from the gastrointestinal tract is fairly rapid. The maximum plasma concentration of propylene glycol in humans is reached within 1 hour after oral exposure, while the elimination half-life is about, 4 hours. The total body clearance is about 0.1 L/kg/hour and seems to be serum-concentration dependent (Yu et al. 1985). Dose-dependent elimination is seen in rats, with saturation of the pathways at doses above 5,880 mg/kg (Morshed et al. 1988). An apparent maximum elimination rate of 8.3 mmol/kg/hour (630 mg/kg/hour) was observed.

 

References

Christopher MM, Perman V, White JG, et al. 1989. Propylene glycol-induced Heinz body formation and D-lactic acidosis in cats. Prog Clin Biol Res 319:69-92.

Huff E. 1961. Metabolism of 1,2-propanediol. Biochim Biophys Acta 48:506-517.

Miller ON, Bazzano G. 1965. Propanediol metabolism and its relation to lactic acid metabolism. Ann NY Acad Sci 119:959-973.

Morshed KM, Nagpaul JP, Majumdar S, et al. 1988. Kinetics of propylene glycol elimination and metabolism in rat. Biochem Med Metab Biol 39(1):90-97.

Morshed KM, Nagpaul JP, Majumdar S, et al. 1989. Kinetics of oral propylene glycol-induced acute hyperlactatemia. Biochem Med Metab Biol 42(2):87-94.

Morshed KM, Helgoualch AL, Nagpaul JP, et al. 1991. The role of propylene glycol metabolism in lactatemia in the rabbit. Biochemical Medicine and Metabolic Biology 46:145-151.

Ruddick JA. 1972. Toxicology, metabolism, and biochemistry of 1,2-propanediol. Toxicol Appl Pharmacol 21(1):102-111.

Yu DK, Elmquist WF, Sawchuk RJ. 1985.Pharmacokinetics of propylene glycol in humans during multiple dosing regimens.J Pharm Sci 74(8):876-879.

Reference 9

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

1990

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Acceptable, well documented publication which meets basic scientific principles.

Justification for type of information:

Please refer section 13 for read across justification.

Reason / purpose for cross-reference:

read-across source

Principles of method if other than guideline:

28-days uptake/4-days depuration study with Lepomis macrochirus under flow-through conditions.

GLP compliance:

no

Radiolabelling:

yes

Details on sampling:

- Sampling intervals/frequency for test organisms: Fish were sampled at 0.5, 1, 2, 4, 8, 14, 21 and 28 days during the exposure phase (5 fish per time point) and at 1, 2 and 4 days during the clearance phase (5 fish per time point).
- Sampling intervals/frequency for test medium samples: Water samples were taken daily. For analysis of parent compound and metabolites water samples from exposure aquarium were analysed at least once a week.
- Sample storage conditions before analysis: immediate analysis
- Details on sampling and analysis of test organisms and test media samples: Water samples were analysed using Liquid Scintillation (LS) counting method. Fish tissue samples were analyzed for radioactivity after combustion.

Vehicle:

yes

Details on preparation of test solutions, spiked fish food or sediment:

PREPARATION AND APPLICATION OF TEST SOLUTION
- Chemical name of vehicle: acetone
- Concentration of vehicle in test medium: 0.095 mL/L in the vehicle control

Test organisms (species):

Lepomis macrochirus

Details on test organisms:

TEST ORGANISM
- Common name: bluegill
- Source: Fish were purchased from Osage Catfisheries of Osage Beach MO, USA.
- Length at study initiation: 3.0 - 4.5 cm
- Weight at study initiation: 0.5 - 0.7 g

ACCLIMATION
- Acclimation period: > 21 days
- Type and amount of food: synthetic diet
- Feeding frequency: ad libitum

Route of exposure:

aqueous

Test type:

flow-through

Water / sediment media type:

natural water: freshwater

Total exposure / uptake duration:

28 d

Total depuration duration:

4 d

Hardness:

73 - 76 mg/L CaCO3

Test temperature:

16.3 - 17.9 °C

pH:

7.7 - 8.1

Dissolved oxygen:

8.1 - 9.6 mg/L

Details on test conditions:

TEST SYSTEM
- Test vessel: aquarium
- Type: covered with plexiglas lids
- Material, size: glass, 40 L
- Aeration: Aquaria were equipped with magnetic stirring bars.
- Type of flow-through: A three-way valve was located between the peristaltic pump and the mixing chambers so that the flow could be measured daily and adjusted.
- Renewal rate of test solution : 6 volume changes every 24 h
- No. of organisms per vessel: 85
- No. of vessels per concentration (replicates): 1 for exposure, 1 for depuration
- No. of vessels per control / vehicle control (replicates): 1

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: Dilution water used was from the upper Saginaw Bay of Lake Huron and was sand filtered, pH adjusted with CO2 to pH 8, carbon filtered and UV-radiated before use.
- Alkalinity: 46 - 52 mg/L as CaCO3
- Conductance: 140 - 150 µmhos/cm
- Intervals of water quality measurement: Temperature, pH and oxygen were measured periodically.

Nominal and measured concentrations:

Nominal: 0 (vehicle control), 0.33 µg/L
Measured: < LOD, 0.29 µg/L (average)

Reference substance (positive control):

no

Details on estimation of bioconcentration:

BASIS FOR CALCULATION OF BCF
- Estimation: Two compartment model is used to describe the uptake and elimination of xenobiotics by fish.

Type:

BCF

Value:

< 17 dimensionless

Basis:

not specified

Remarks on result:

other: Conc.in environment / dose:0.29 µg/L (measured average)

Metabolites:

Haloxyfop, polar metabolites 1 and 2.

Bluegill exposed to 14C haloxyfop-methyl for 28 days were found to rapidly absorb the ester from water which was then biotransformed at an extremely fast rate within the fish such that essentially no haloxyfop-methyl was detected in the fish. The estimated bioconcentration factor for the haloxyfop-methyl in whole fish was < 17, based upon the detection limit for ester in fish and the average concentration of haloxyfop-methyl in exposure water. The total 14C residue level within whole fish averaged about 0.27 µg/g equivalents over the course of the uptake phase. The principal component of the 14C residue was haloxyfop, which accounted for an average of about 60% of the radioactivity. Two other polar metabolites were detected in the fish which accounted for an average of about 14% of the radioactivity and an average of about 25% of the radioactivity. Once the fish were transferred to clean water, all metabolites cleared quickly with similar clearance rates. A simulation model estimated the uptake rate constant of haloxyfop-methyl from water to be about 720 mL/g*day. The rate constants for biotransformation of haloxyfop-methyl and the clearance of metabolites formed were estimated to be 200/day (DT50 = 5 min) and 0.82/day (DT50 = 0.8 days), respectively. The high rate of biotransformation of the parent compound within the fish demonstrates the importance of basing the bioconcentration factor upon the actual concentration of parent material within the organisms rather than the total radioactive residue levels for radiolabeled bioconcentration studies.

Description of key information

The BCF of the main component 2-[(Z)-octadec-9-enoyl]oxypropyl (Z)-octadec-9-enoate of the test substance was calculated to be 641.5 L/Kg wet-wt using a measured log Kow of 8.46, but by taking into account all relevant data for the assessment of the bioaccumulation potential, it can be concluded that test substance has a low potential for bioaccumulation and biomagnification through the food chain.

If aquatic exposure occurs, the substance will be mainly taken up by ingestion and digested through common metabolic pathways providing a valuable energy source for the organisms as dietary fats.

Glycol esters are not expected to bioaccumulate in aquatic or sediment organisms and secondary poisoning does not pose a risk.

Key value for chemical safety assessment

BCF (aquatic species):

641.5 L/kg ww

Additional information

Experimental bioaccumulation data are not available. The high log Kow of 8.47 and calculated BCF (641.5 L/Kg ww) indicates a potential for bioaccumulation. But it does not reflect the behavior of the substance in the environment and the metabolism in living organisms.

 

Environmental behavior

Due to ready biodegradability and high potential of adsorption, the substance can be effectively removed in conventional STPs either by biodegradation or by sorption to biomass. The low water solubility and high estimated log Kow indicate the substance is highly lipophilic. If released into the aquatic environment, the substance undergoes extensive biodegradation and sorption on organic matter, as well as sedimentation. The bioavailability of the substance in the water column is reduced rapidly. The relevant route of uptake of glycol ester in organisms is considered predominately by ingestion of particle bounded substance. 

 

Metabolism of aliphatic esters

Should the substance be taken up by fish during the process of digestion and absorption in the intestinal tissue, aliphatic esters like glycol esters are expected to be initially metabolized via enzymatic hydrolysis in the corresponding free fatty acids and the free glycol alcohols such as ethylene glycol and propylene glycol. The hydrolysis is catalyzed by classes of enzymes known as carboxylesterases or esterases (Heymann, 1980). The most important of which are the B-esterases in the hepatocytes of mammals (Heymann, 1980; Anders, 1989). Carboxylesterase activity has been noted in a wide variety of tissues in invertebrates as well as in fish (Leinweber, 1987; Suldano et al, 1992; Barron et al., 1999, Wheelock et al., 2008). The catalytic activity of this enzyme family leads to a rapid biotransformation/metabolism of xenobiotics which reduces the bioaccumulation or bioconcentration potential (Lech &, 1980). It is known for esters that they are readily susceptible to metabolism in fish (Barron et al., 1999) and literature data have clearly shown that esters do not readily bioaccumulate in fish (Rodger & Stalling, 1972; Murphy & Lutenske, 1990; Barron et al., 1990). In fish species, this might be caused by the wide CaE distribution, high tissue content, rapid substrate turnover and limited substrate specificity (Lech & Melancon, 1980; Heymann, 1980).

 

Metabolism of enzymatic hydrolysis products

Ethylene glycol and propylene glycol are the expected corresponding alcohol metabolites from the enzymatic reaction of the Glycol esters. Ethylene glycol and propylene glycol are rapidly absorbed from the gastrointestinal tract and then undergo rapid biotransformation in liver and kidney (WHO, 2002a, ATSDR, 1997). Propylene glycol will be further metabolized in liver by alcohol dehydrogenase to lactic acid and pyruvic acid which are endogenous substances naturally occurring in mammals (Miller & Bazzano, 1965, Ritchie, 1927). Ethylene glycol is first metabolised by alcohol dehydrogenase to glycoaldehyde, which is then further oxidized successively to glycolic acid, glyoxylic acid, oxalic acids by mitochondrial aldehyde dehydrogenase and cytosolic aldehyde oxidase (ATSDR, 2010; WHO, 2002a). The metabolite ethylene glycol is toxic to human and mammalian, but it has generally low toxicity to aquatic organisms and is not expected to bioaccumulate based on the low log Kow (WHO, 2002a; WHO, 2002b). Safety evaluation of propylene glycol indicated a low toxicity to human and mammalian and the aquatic compartment. (OECD, 2001).

 

Lipids and their key constituent fatty acids are, along with protein, the major organic constitute of fish and they play a major role as sources of metabolic energy in fish for growth, reproduction and movement, including migration (Tocher, 2003). In fishes, the fatty acids metabolism in cell covers the two processes anabolism and catabolism. The anabolism of fatty acids occurs in the cytosol, where fatty acids esterified into cellular lipids that is the most important storage form of fatty acids. The catabolism of fatty acids occurs in the cellular organelles, mitochondria and peroxisomes via a completely different set of enzymes. The process is termed ß-oxidation and involves the sequential cleavage of two-carbon units, released as acetyl-CoA through a cyclic series of reaction catalyzed by several distinct enzyme activities rather than a multienzyme complex (Tocher, 2003).

As fatty acids are naturally stored in fat tissue and re-mobilized for energy production is can be concluded that even if they bioaccumulate, bioaccumulation will not pose a risk to living organisms. Fatty acids (typically C14 to C24 chain lengths) are also a major component of biological membranes as part of the phospholipid bilayer and therefore part of an essential biological component for the integrity of cells in every living organism (Stryer, 1994).

 

Data from QSAR calculation

Additional information about this endpoint could be gathered through BCF/BAF calculation using BCFBAF v3.01 (Werth, 2014). The estimated BCF value indicates a BCF of 641.5 L/kg wet-wt from regression based method.

Conclusion

The estimated BCF value indicates a BCF of 641.5 L/kg wet-wt from regression based method. Nevertheles, Aliphatic esters are biotransformed to fatty acids and the corresponding alcohol component by the ubiquitous carboxylesterase enzymes in aquatic species. Based on the rapid metabolism it can be concluded that the high log Kow, which indicates a potential for bioaccumulation, overestimates the bioaccumulation potential of the glycol esters.

For a detailed reference list please refer to the CSR or IUCLID section 13.