Soybean oil, maleated, ester with triethanolamine

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Remarks:

Expert statement

Type of information:

other: Expert statement

Adequacy of study:

key study

Study period:

N/A

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Expert statement

Data source

Reference

Reference Type:

other: Expert statement

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Objective of study:

other: The toxicokinetic profile of the substance was predicted using the physical chemical properties of the substance, the data obtained from acute and repeated-dose toxicity studies, as well as information gained from genotoxicity assays.

Test guideline

Qualifier:

no guideline required

Version / remarks:

The toxicokinetic profile of the substance was predicted using the physical chemical properties of the substance, the data obtained from acute and repeated-dose toxicity studies, as well as information gained from genotoxicity assays.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Soybean oil, maleated, ester with triethanolamine

EC Number:

285-107-2

EC Name:

Soybean oil, maleated, ester with triethanolamine

Cas Number:

85029-82-9

Molecular formula:

C63H113NO12 to C67H123NO12

IUPAC Name:

Soybean oil, maleated, ester with triethanolamine

Test material form:

other: Clear amber viscous liquid

Details on test material:

100% product
Physical state/Appearance: Clear amber viscous liquid
Expiry Date: 24 June 2018
Storage Conditions: Room temperature in the dark

Specific details on test material used for the study:

The toxicokinetic profile of the substance was predicted using the physical chemical properties of the substance, the data obtained from acute and repeated-dose toxicity studies, as well as information gained from genotoxicity assays.

Radiolabelling:

no

Test animals

Species:

other: N/A

Strain:

other: N/A

Details on species / strain selection:

N/A

Sex:

not specified

Details on test animals or test system and environmental conditions:

N/A

Administration / exposure

Route of administration:

other: N/A

Vehicle:

other: N/A

Results and discussion

Any other information on results incl. tables

Absorption

 

Oral Route

The physical chemical properties described above indicate that the substance has a nominal molecular size within the range (<500) that may be expected to be absorbed within the mammalian gastrointestinal tract, should that material be ingested. However, being extremely lipophilic the substance may be expected not to easily cross gastrointestinal epithelial barriers. It may participate in micellar transport into the hepatic portal system along with other lipophilic substances (e.g., dietary fats). An acute oral gavage toxicity study identified no evidence of toxicity (LD50 >2000 mg/kg bw). The repeat dose and reproductive screening toxicology study using the oral route gave a NOAEL of 1000 mg/kg bw/day. The absence of adverse findings following oral dosing may be due to non-absorbance via the GI tract or to a low index of inherent toxicity for the substance and/or its metabolite(s).

 

 

Dermal Route

Regarding the dermal absorption of the substance, its rate of uptake into the stratum corneum and its rate of transfer between the stratum corneum and the epidermis are likely to be slow considering both the log Pow, and its water solubility. These assumptions were supported by the absence of observed systemic effects following dermal application of the substance in the acute dermal toxicity study at up to 2000 mg/kg bw. Furthermore, the substance caused no irritant effects after dermal exposure and so there would be no facilitation of absorption through the skin after prolonged exposure.

 

Inhalation Route

The potential for inhalation toxicity was not studied directly in a toxicology study using the inhalation route. However, the physical nature of the substance (viscous liquid) and low vapour pressure of the substance indicate a very low propensity to enter atmospheric air in a respirable form. Thus, respiratory absorption under normal use and based on the life-cycle information of this substance, is expected to be inconsequential.

 

Distribution

 

Systemic distribution of the substance can be predicted from the physical chemical properties of this substance. The very high LogPow and modest water solubility of the substance, suggests that this substance, upon systemic absorption, may be transported through the circulatory system both in association with a carrier molecule such as a lipoprotein or other macromolecules. The major proportion of the substance will not readily traverse cellular barriers or distribute into fatty tissues. There is no evidence of systemic toxicity and/or histopathological changes or increasing severity of clinical observations from repeated dose studies, nor of cumulative toxicity, as would be manifested by an accumulation of the substance or its’ metabolites in body tissues.

 

Metabolism

 

The substance is a UVCB and like most xenobiotics, it may be expected to undergo phase I oxidation/reduction, esterase-catalyzed hydrolysis and subsequent Phase II conjugation. Acute and repeated-dose toxicity testing provided no evidence that the substance was metabolized into toxic metabolites. Data from bacterial mutagenicity and mammalian cell mutagenicity tests in mammalian cells, in which the substance was subjected to rat hepatic microsomal enzyme systems, did not show any evidence of genotoxic activity from the substance or its metabolites. Furthermore, the substance was not toxic in vitro either in the presence or absence of metabolic enzymes.

 

Excretion

 

The structural characteristics of the substance suggest that this molecule may undergo phase I and phase II metabolic transformation. The resulting metabolic by-products are expected to undergo routine renal and or biliary excretion.

Applicant's summary and conclusion

Executive summary:

Absorption

 

Oral Route

The physical chemical properties described above indicate that the substance has a nominal molecular size within the range (<500) that may be expected to be absorbed within the mammalian gastrointestinal tract, should that material be ingested. However, being extremely lipophilic the substance may be expected not to easily cross gastrointestinal epithelial barriers. It may participate in micellar transport into the hepatic portal system along with other lipophilic substances (e.g., dietary fats). An acute oral gavage toxicity study identified no evidence of toxicity (LD50 >2000 mg/kg bw). The repeat dose and reproductive screening toxicology study using the oral route gave a NOAEL of 1000 mg/kg bw/day. The absence of adverse findings following oral dosing may be due to non-absorbance via the GI tract or to a low index of inherent toxicity for the substance and/or its metabolite(s).

 

 

Dermal Route

Regarding the dermal absorption of the substance, its rate of uptake into the stratum corneum and its rate of transfer between the stratum corneum and the epidermis are likely to be slow considering both the log Pow, and its water solubility. These assumptions were supported by the absence of observed systemic effects following dermal application of the substance in the acute dermal toxicity study at up to 2000 mg/kg bw. Furthermore, the substance caused no irritant effects after dermal exposure and so there would be no facilitation of absorption through the skin after prolonged exposure.

 

Inhalation Route

The potential for inhalation toxicity was not studied directly in a toxicology study using the inhalation route. However, the physical nature of the substance (viscous liquid) and low vapour pressure of the substance indicate a very low propensity to enter atmospheric air in a respirable form. Thus, respiratory absorption under normal use and based on the life-cycle information of this substance, is expected to be inconsequential.

 

Distribution

 

Systemic distribution of the substance can be predicted from the physical chemical properties of this substance. The very high LogPow and modest water solubility of the substance, suggests that this substance, upon systemic absorption, may be transported through the circulatory system both in association with a carrier molecule such as a lipoprotein or other macromolecules. The major proportion of the substance will not readily traverse cellular barriers or distribute into fatty tissues. There is no evidence of systemic toxicity and/or histopathological changes or increasing severity of clinical observations from repeated dose studies, nor of cumulative toxicity, as would be manifested by an accumulation of the substance or its’ metabolites in body tissues.

 

Metabolism

 

The substance is a UVCB and like most xenobiotics, it may be expected to undergo phase I oxidation/reduction, esterase-catalyzed hydrolysis and subsequent Phase II conjugation. Acute and repeated-dose toxicity testing provided no evidence that the substance was metabolized into toxic metabolites. Data from bacterial mutagenicity and mammalian cell mutagenicity tests in mammalian cells, in which the substance was subjected to rat hepatic microsomal enzyme systems, did not show any evidence of genotoxic activity from the substance or its metabolites. Furthermore, the substance was not toxic in vitro either in the presence or absence of metabolic enzymes.

 

Excretion

 

The structural characteristics of the substance suggest that this molecule may undergo phase I and phase II metabolic transformation. The resulting metabolic by-products are expected to undergo routine renal and or biliary excretion.