Reaction product of n-nonanoic acid (C9), n-heptanoic acid (C7), n-pentanoic acid (C5), mixed tetraesters with pentaerythritol, and 3,5,5-trimethylhexanoic acid

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not specified

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study produced using data from results undertaken following OECD and EU test guidelines performed by a GLP accredited laboratory.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

Summary based upon experimental results of the test substance.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Isononanoic Acid, Mixed Esters with Heptanoic Acid and Pentaerythritol

Cas Number:

118685-29-3

Molecular formula:

C33H60O8 to C41H76O8 (in C2H4 unit increments).

IUPAC Name:

Isononanoic Acid, Mixed Esters with Heptanoic Acid and Pentaerythritol

Test material form:

other: liquid

Details on test material:

Not specified in the summary report

Radiolabelling:

no

Test animals

Species:

other: various

Details on test animals or test system and environmental conditions:

Various test animals used in the studies which have provided the results for the assessment.

Administration / exposure

Route of administration:

other: various

Details on exposure:

Various different exposures routes have been detailed in the assessment based on experiments performed using the test substance

Duration and frequency of treatment / exposure:

Various durations and frequency's have been used in the studies which have provided the results for the assessment.

Doses / concentrations

Remarks:

Doses / Concentrations:
Various doses/concentrations have been used in the studies which have provided the results for the assessment.

No. of animals per sex per dose / concentration:

Various numbers animals used in the studies which have provided the results for the assessment.

Details on study design:

Various different studies used which have provided the results for the assessment.

Details on dosing and sampling:

Various dosing and sampling methods used in the studies which have provided the results for the assessment.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): low bioaccumulation potential based on study results

Executive summary:

The pentaeryhritol family consists of 13 substances, which are all pentaeryhritol esters with linear and branched carboxylic acids C5-C10. All substances are clear colourless to light yellow liquids.

 

The acute oral and dermal toxicity tests with the different members of pentaeryhritol family showed the LD50 being high in all cases. For oral administration the LD50 ranged from > 01940 to >5000 mg/kg/day and for dermal administration the LD50 was higher than 2000 mg/kg body weight. The subacute toxicity test for 28 -days revealed a NOAEL ranging from 150 to 1000 mg/g/day. Therefore, an extensive toxicokinetic assessment is considered of limited value. Below, a summary of the anticipated toxicokinetic behaviour of the pentaeryhritol family is given.

 

The water solubility of the pentaeryhritol family is low (< 01 - < 0.5 mg/l), caused by the presence of the strongly apolar aliphatic chains. Since in general a compound needs to be dissolved before it can be taken up from the gastro-intestinal tract, it is unlikely that the pentaeryhrilol family wil show a high systemic exposure after oral administration. However, in the presence of food and bile salts, the solubility will probably be increased and thus the systemic exposure might be higher. For compounds with a high partition coeffcient like the pentaeryhritol family also direct uptake via the lymph is sometimes observed. It is to be expected that the oral bioavailability, and thus the systemic exposure, of the pentaeryhritol family will be relatively low.

In the case absorption of the pentaeryhritol family occurs, extensive cleavage of the ester bonds is anticipated. The aliphatic chains will probably undergo extensive hydroxylation, followed by rapid sulfation or glucuronidation. The resulting metabolites will be extensively excreted via bile and/or urine.

The pentaeryhritol familywill show a high volume of distribution, because of the high lipophilcity of the compounds. They will be extensively distributed into peripheral tissue,especially fatty tissues. Accumulation in fatty tissues is therefore anticipated. The plasmaprotein binding is expected to be high.

Uptake via inhalation is unlikely because of the relatively large particles.

Since it is generally accepted that substances with log Po/w ranging from 0.1 to 6 penetrate the skin easily, it is to be expected that the pentaeryhritol family in general hardly penetrates theskin.

Based on the expected kinetic behaviour in the body, as described above, the members of the pentaeryhrilol family will hardly be absorbed after oral administration, mainly because of their low solubility. If absorption occurs, these compounds will be extensively metabolised in the liver or plasma and rapidly excreted via bile and/or urine. Therefore, accumulation in the body during prolonged exposure will be very low, although some retention in fatty tissues may occur.

Since the chemical structures of the members of the pentaeryhritol family are strongly comparable, and the physical, chemical, and toxicological data are in a narrow range, it is to be expected that the toxicokinetic behaviour of the different compounds will follow the same pattern.