Fatty acids, C5-10, esters with pentaerythritol

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

bioaccumulation in aquatic species, other

Type of information:

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

Remarks:

2 substances are available for read across combined with literature data

Adequacy of study:

weight of evidence

Justification for type of information:

see the attached justification in section 13 for details

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Principles of method if other than guideline:

Calculation based on BCFBAF v3.01, Estimation Programs Interface Suite™ for Microsoft® Windows v 4.10. 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: 16.56 (estimated, KOWWIN v.1.68)

Key result

Type:

BAF

Value:

0.893 L/kg

Basis:

whole body w.w.

Remarks on result:

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

Remarks:

3-(decanoyloxy)-2,2-bis[(decanoyloxy)methyl]propyl decanoate (CAS 13784-61-7)

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)

Remarks:

3-(decanoyloxy)-2,2-bis[(decanoyloxy)methyl]propyl decanoate (CAS 13784-61-7)

Key result

Type:

BAF

Value:

6.323 L/kg

Basis:

whole body w.w.

Remarks on result:

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

Remarks:

3-(pentanoyloxy)-2,2-bis[(pentanoyloxy)methyl]propyl valerate (CAS 15834-04-5)

Key result

Type:

BCF

Value:

6.322 L/kg

Basis:

whole body w.w.

Remarks on result:

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

Remarks:

3-(pentanoyloxy)-2,2-bis[(pentanoyloxy)methyl]propyl valerate (CAS 15834-04-5)

Key result

Type:

BCF

Value:

< 17 dimensionless

Basis:

not specified

Remarks on result:

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

Remarks:

methyl2-(4-((3-chloro-5-(trifluoromethyl)-2-pyridinyl)oxy)phenoxy) propanoate

Key result

Type:

BCF

Value:

3.16 L/kg

Basis:

whole body w.w.

Remarks on result:

other: regression-based estimate

Remarks:

3-(decanoyloxy)-2,2-bis[(decanoyloxy)methyl]propyl decanoate (CAS 13784-61-7)

Key result

Type:

BCF

Value:

550 L/kg

Basis:

whole body w.w.

Remarks on result:

other: regression-based estimate

Remarks:

3-(pentanoyloxy)-2,2-bis[(pentanoyloxy)methyl]propyl valerate (CAS 15834-04-5)

Biotransformation Rate Constant:

kM (Rate Constant): 0.3728 /day (10 gram fish)

kM (Rate Constant): 0.2097 /day (100 gram fish)

kM (Rate Constant): 0.1179 /day (1 kg fish)

kM (Rate Constant): 0.0663 /day (10 kg fish)

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) = -0.049 (BAF = 0.893 L/kg wet-wt)

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

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

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

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

Arnot-Gobas BCF & BAF Methods (assuming a biotransformation rate of zero):

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

Validity criteria fulfilled:

not applicable

Remarks:

read across

Conclusions:

The substance, CAS 68424-31-7 ; EC 270-291-9, is analogous to the substances to be
read across to, in terms of basic form, and the degree of substitution of functional groups
is not considered to effect the proposed read across for the endpoint of bioaccumulation. Based on the available information to read across to, the substance is not expected to be bioaccumulative.

Reference 2

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented publication which meets basic scientific principles

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

Key result

Remarks on result:

other: Precise results cannot be given, see explanation in any other information on results incl. tables.

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 3

Endpoint:

bioaccumulation: aquatic / sediment

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data from review article/book chapter.

Qualifier:

no guideline followed

Principles of method if other than guideline:

no data

GLP compliance:

no

Test organisms (species):

other: not applicable

Route of exposure:

other: not applicable

Key result

Remarks on result:

other: Precise results cannot be given, see explanation in any other information on results incl. tables.

Carboxylesterases are a class of enzymes responsible for the ester cleavage of carboxylic esters. Liver B-carboxylesterases are the most prominent group of all “nonspecific” ester-cleaving enzymes. The preferred substrates of B-esterases are aliphatic esters. B-type esterases have been characterized in human muscle, kidney, brain, liver and serum of mammals. The activity of B-esterase from pig and rat liver was shown for several carboxylesters (e.g. methyl octanoate, heptyl acetate).

Reference 4

Endpoint:

bioaccumulation: aquatic / sediment

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data from review article.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Review article, describing biotransformation reactions and their effect on toxicity and bioaccumulation of certain chemicals in fish.

GLP compliance:

no

Test organisms (species):

other: not applicable

Route of exposure:

other: not applicable

Test type:

other: not applicable

Remarks on result:

other: Precise results cannot be given, see explanation in any other information on results incl. tables.

The catalytic activity of the carboxylesterase family leads to a rapid biotransformation/metabolism of xenobiotics which reduces the bioaccumulation or bioconcentration potential. Several in-vivo and in-vitro experiments showed the biotransformation of xenobiotics in fish. The biotransformation reactions have been shown to occur in fish at rates which have siginificant effects on toxicity and residue dynamics of selected chemicals. Inhibition of these reactions can lead to increased toxicity and bioaccumulation factors. Thus, it was shown that the carboxylesterase activity has an influence on the bioaccumulation of xenobiotics.

Reference 5

Endpoint:

bioaccumulation: aquatic / sediment

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Qualifier:

no guideline followed

Principles of method if other than guideline:

The study was conducted to examine the effects and fate of a number of chemicals, including hydrocarbons and chlorinated hydrocarbons. The interactions between these chemicals in fish were studied using several approaches: examination of the uptake, metabolism and elimination of selected chemicals by fish; assessment of the effects of selected inducing agents on hepatic xenobiotic metabolizing enzymes (assayed in vitro); and studies of the effects of inducing agents on the metabolism and disposition of other chemicals in vitro.

GLP compliance:

no

Test organisms (species):

other: Salmo gairdneri, Lepomis macrochirus, Cyprinus carpio and Archosargus probatocephalus

Route of exposure:

other: intraperitoneal injection

Key result

Remarks on result:

other: Precise results cannot be given, see explanation in any other information on results incl. tables.

Esters do not readily bioaccumulate in fish. This might be caused by the wide carboxyesterase distribution, high tissue content, rapid substrate turnover and limited substrate specificity.

Reference 6

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented publication which meets basic scientific principles.

Qualifier:

no guideline followed

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.

Key result

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 7

Endpoint:

bioaccumulation in aquatic species, other

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Validated QSAR model. Calculation for main component of Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids, 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: 16.56). 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: migrated from IUCLID 5.6

Principles of method if other than guideline:

Calculation based on BCFBAF v3.01, Estimation Programs Interface Suite™ for Microsoft® Windows v 4.10. 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: 16.56 (estimated, KOWWIN v.1.68)

Key result

Type:

BAF

Value:

0.893 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)

Biotransformation Rate Constant:

kM (Rate Constant): 0.3728 /day (10 gram fish)

kM (Rate Constant): 0.2097 /day (100 gram fish)

kM (Rate Constant): 0.1179 /day (1 kg fish)

kM (Rate Constant): 0.0663 /day (10 kg fish)

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) = -0.049 (BAF = 0.893 L/kg wet-wt)

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

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

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

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

Arnot-Gobas BCF & BAF Methods (assuming a biotransformation rate of zero):

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

Reference 8

Endpoint:

bioaccumulation in aquatic species, other

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Validated QSAR model. Calculation for main component of Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids, however the component is outside of the domain of the training set (log Kow of the training set: 1 - 11.26; log Kow of the component: 16.56). 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: migrated from IUCLID 5.6

Principles of method if other than guideline:

Calculation based on BCFBAF v3.01, Estimation Programs Interface Suite™ for Microsoft® Windows v 4.10. 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: 16.56 (estimated, KOWWIN v.1.68)

Key result

Type:

BCF

Value:

3.16 L/kg

Basis:

whole body w.w.

Remarks on result:

other: regression-based estimate

Reference 9

Endpoint:

bioaccumulation in aquatic species, other

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Validated QSAR model. Calculation for main component of tetraester component of Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Principles of method if other than guideline:

Calculation based on BCFBAF v3.01, Estimation Programs Interface Suite™ for Microsoft® Windows v 4.10. 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: 6.74 (estimated, KOWWIN v.1.68)

Key result

Type:

BAF

Value:

6.323 L/kg

Basis:

whole body w.w.

Remarks on result:

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

Key result

Type:

BCF

Value:

6.322 L/kg

Basis:

whole body w.w.

Remarks on result:

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

Biotransformation Rate Constant:

kM (Rate Constant): 25 /day (10 gram fish) **

kM (Rate Constant): 14.06 /day (100 gram fish) **

kM (Rate Constant): 7.906 /day (1 kg fish) **

kM (Rate Constant): 4.446 /day (10 kg fish) **

** Predicted value exceeds theoretical whole body maximum value.

kM (Rate Constant) of 25 /day is recommended/applied for 10 g fish

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

Estimated Log BCF (upper trophic) = 0.801 (BCF = 6.322 L/kg wet-wt)

Estimated Log BAF (upper trophic) = 0.801 (BAF = 6.323 L/kg wet-wt)

Estimated Log BCF (mid trophic) = 0.924 (BCF = 8.39 L/kg wet-wt)

Estimated Log BAF (mid trophic) = 0.958 (BAF = 9.073 L/kg wet-wt)

Estimated Log BCF (lower trophic) = 0.962 (BCF = 9.164 L/kg wet-wt)

Estimated Log BAF (lower trophic) = 1.457 (BAF = 28.67 L/kg wet-wt)

Arnot-Gobas BCF & BAF Methods (assuming a biotransformation rate of zero):

Estimated Log BCF (upper trophic) = 4.192 (BCF = 1.555e+004 L/kg wet-wt)

Estimated Log BAF (upper trophic) = 6.982 (BAF = 9.59e+006 L/kg wet-wt)

Reference 10

Endpoint:

bioaccumulation in aquatic species, other

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Validated QSAR model. Calculation for main component of Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids.

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Principles of method if other than guideline:

Calculation based on BCFBAF v3.01, Estimation Programs Interface Suite™ for Microsoft® Windows v 4.10. 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: 6.74 (estimated, KOWWIN v.1.68)

Key result

Type:

BCF

Value:

550 L/kg

Basis:

whole body w.w.

Remarks on result:

other: regression-based estimate

Reference 11

Endpoint:

bioaccumulation: aquatic / sediment

Type of information:

other: review article

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented publication which meets basic scientific principles.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Review article describing the metabolism and functions of lipids and fatty acids in fish. Both play major roles as source of metabolic energy in processes as growth and reproduction.

GLP compliance:

no

Test organisms (species):

other: Fish

Route of exposure:

other: not applicable, review article

Test type:

other: not applicable, review article

Key result

Remarks on result:

other: Precise results cannot be given, see explanation in any other information on results incl. tables.

- Fatty acid catabolism is the predominant source of energy in many species of fish. The catabolism of fatty acids occurs in the cellular organelles, mitochondria (and peroxisomes). The process is termed beta-oxidation and involves the sequential cleavage of two-carbon units, released as acetyl-CoA, through a cyclic series of reactions catalyzed by several distinct enzyme activities. Activated fatty acids are transported to the mitochondrion in the form of fatty acyltransferase, converted back into fatty acyl-CoA derivatives, and then undergo a round of dehydrogenation, hydration, second hydrogenation, and cleavage steps to produce acetyl-CoA and NADH. Then, the acetyl-CoA can be metabolized via the tricarboxylic cycle to produce more NADH. The NADH will eventually lead to the release of ATP through the process of oxidative phosphorilation, available to be used as energy source.

- Fatty acid oxidation is an important source of energy in several tissues in fish (heart, red muscles, etc). Furthermore, fatty acids are the major source of metabolic energy in the development from egg to adult fish and also during reproduction and lipid depletion processes, such as migrations. They are also involved in the maintainance of the structure and function of cellular biomembranes (as part of phosphoglycerides).

Description of key information

If aquatic exposure occurs, polyol esters category members will be mainly taken up by ingestion and digested through common metabolic pathways providing a valuable energy source for the organisms as dietary fats. The category members are not expected to bioaccumulate in aquatic or sediment organisms and secondary poisoning does not pose a risk.

Additional information

Aquatic bioaccumulation

Experimental bioaccumulation data are not available for the members of the polyol ester category. The high log Kow as an intrinsic property of the category members 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 fate

Due to ready biodegradability and high potential of adsorption, the category members 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 polyol esters in organisms is considered predominately by ingestion of particle bounded substance.

 

Metabolism of polyol esters

Should the substance be taken up by fish during the process of digestion and absorption in the intestinal tissue, polyol esters are expected to be initially metabolized via enzymatic hydrolysis in the corresponding free fatty acids and the free alcohols such as neopentylglycol (NPG), trimethylolpropane (TMP), pentaerythritol (PE) and dipentaerythritol (DiPE). 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 & Bend, 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

Neopentylglycol (NPG), trimethylolpropane (TMP), pentaerythritol (PE) and dipentaerythritol (DiPE) are the expected possible corresponding alcohol metabolites from the enzymatic reaction of the polyol ester category members. In general, the hydrolysis rate of fatty acid esters and polyol ester in particular varies depending on the fatty acid chain length, and grade of esterification (Mattson and Volpenhein, 1969; Mattson and Volpenhein, 1972a,b).

In the gastrointestinal GI tract(GIT), metabolism prior to absorption via gut microflora or enzymes in the GI mucosa may occur. In fact, after oral ingestion, fatty acid esters with glycerol (glycerides) are rapidly hydrolized by ubiquitously expressed esterases and almost completely absorbed (Mattson and Volpenhein, 1972a).The result of the pancreatic digestion of one NPG ester shows a degradation of the ester of almost 90% within 4 hours (Oßberger, 2012). In contrast with regard to the Polyol esters it was shown that lower rate of enzymatic hydrolysis in the GIT were showed for compounds with more than 3 ester groups (Mattson and Volpenhein, 1972a,b). In vitro hydrolysis rate of pentaerythritol ester was about 2000 times slower in comparison to glycerol esters (Mattson and Volpenhein, 1972a,b).

When hydrolysis occurs the potential hydrolysis products are absorbed and subsequently enter the bloodstream. Potential cleavage products are stepwise degraded via beta–oxidation in the mitochondria. Even numbered fatty acids are degraded via beta-oxidation to carbon dioxide and acetyl-CoA, with release of biochemical energy. In contrast, the metabolism of the uneven fatty acids results in carbon dioxide and an activated C3-unit, which undergoes a conversion into succinyl-CoA before entering the citric acid cycle (Stryer, 1994). Alternative oxidation pathways (alpha- and omega-oxidation) are available and are relevant for degradation of branched fatty acids.

The other cleavage products Polyols (NPG, TMP and PE) are easily absorbed and can either remain unchanged (PE) or may further be metabolized or conjugated (e.g. glucuronides, sulfates, etc.) to polar products that are excreted in the urine (Gessner et al. 1960, Di Carlo et al., 1964).

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 beta-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. The estimated BCF value indicates a low bioaccumulation in organisms (BCF: 3.16 - 550 L/kg, regression based). When including biotransformation rate constants a BCF of 0.89 – 39.11 and a BAF of 0.89 – 153.3 L/kg resulted (Arnot-Gobas estimate, including biotransformation, upper trophic). Even though the members of the polyol ester category are outside the applicability domain of the model they might be used as supporting indication that the potential of bioaccumulation is low. The model training set is only consisting of substances with log Kow values of 0.31 - 8.70. But it supports the tendency that substances with high log Kow values (> 5) have a lower potential for bioconcentration as summarized in the ECHA Guidance R.11 and they are not expected to meet the B/vB criterion (ECHA, 2012).

 

Conclusion

Polyol 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 polyol ester category members. Taking all these information into account, it can be concluded that the bioaccumulation potential of the polyol ester category members is assumed to be low.

A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within CSR.