Fatty acids, C6-12, mixed tetraesters with heptanoic acid, pentaerythritol, 3,5,5-trimethylhexanoic acid and valeric acid

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Type of information:

other: Written assessment based on the available information

Adequacy of study:

key study

Study period:

November 2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: non-GLP assessment report

Materials and methods

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

451-190-0

EC Name:

-

Cas Number:

156558-98-4

Molecular formula:

C25H44O8 to C43H80O8

IUPAC Name:

3-(heptanoyloxy)-2-[(heptanoyloxy)methyl]-2-[(pentanoyloxy)methyl]propyl octanoate

Results and discussion

Any other information on results incl. tables

 Summary and discussion of toxicokinetics

 

This assessment of the toxicokinetic properties of Reaction product of pentanoic acid, C6-C12 mixed fatty acids, pentaerythritol, heptanoic acid and 3,5,5-trimethylhexanoic acid is based on the results obtained with the test substance and read-across substances for the toxicological end‑points listed below and with reference to relevant physico-chemical data:

 

·       acute oral toxicity

·       acute dermal toxicity

·       skin irritation

·       skin sensitisation

·       subacute (28 day) repeated dose toxicity studies

·       reproductive toxicity study

·      developmental study

·       bacterial reverse mutation test

·       in vitro chromosome aberration test

·       in vitro mammalian gene mutation test

 

Reaction product of pentanoic acid, C6-C12 mixed fatty acids, pentaerythritol, heptanoic acid and 3,5,5-trimethylhexanoic acid is a UVCB substance. The most abundant species present in the substance have molecular weights between 472.61 - 725.09 g/mol. The substance has an estimated water solubility of 8.5E^-4mg/L at 20 °C, vapour pressure of 0.003 Pa and a log Kow of 9.18.

 

Four acute oral toxicity studies from read-across substances are detailed below:

·              Decanoic acid, mixed esters with octanoic acid, pentaerythritol and valeric acid (CAS 70693-33-3) was administered to rats via oral gavage to three Wistar rats of each sex at 2000 mg/kg bodyweight. Animals were subjected to daily observations and weekly determination of bodyweight. Macroscopic examination was performed after terminal sacrifice (day 15). Hunched posture was noted in all animals on day 1, but no other effects were observed. No mortality occurred, body weights were within normal range and no abnormalities were found at a macroscopic level. The oral LD50 value in Wistar rats was established to exceed 2000 mg/kg bw.

·              Isooctanoic acid, mixed tetraesters with pentaerythritol, 3,5,5-trimethylhexanoic acid and valeric acid (CAS 144911-11-9) was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kg bodyweight. Animals were subjected to daily observations and weekly determination of bodyweight. Macroscopic examination was performed after terminal sacrifice (day 15). Hunched posture and piloerection were observed among all females on day 1. Males were without clinical signs. but no other effects were observed. No mortality occurred, body weights were within normal range and no abnormalities were found at a macroscopic level. The oral LD50 value in Wistar rats was established to exceed 2000 mg/kg bw.

·              Pentaerythritol mixed tetraesters with 2-ethylhexanoic acid, nananoic acid, and pentanoic acid (CAS 156559-00-1) administered by oral gavage to three Wistar rats of each sex at 2000 mg/kgbodyweight. Animals were subjected to daily observations and weekly determination of bodyweight. Macroscopic examination was performed after terminal sacrifice (day 15). Hunched posture and piloerection were shown by all males on day 1 and by all females between days 1 and 3. In addition, all males showed lethargy on day 1, but no other effects were observed. No mortality occurred, body weights were within normal range and no abnormalities were found at a macroscopic level. The oral LD50 value in Wistar rats was established to exceed 2000 mg/kg bw.

·              Reaction product of pentaerythritol and trimethylolpropane with n-pentanoic acid, 2-methylbutyric acid, n-heptanoic acid, 3,5,5-trimethylhexanoic acid, n-octanoic acid and n-decanoic acid was administered to Sprague-Dawley CD rats via oral gavage at 5000 mg/kg bw. Under the conditions of the study no mortality, clinical signs, effect on body weight or abnormalities at a macroscopic level were observed. The oral LD50 value in Wistar rats was established to exceed 5000 mg/kg bw.

 

Four acute dermal toxicity studies from read-across substances are detailed below:

·              Decanoic acid, mixed esters with octanoic acid, pentaerythritol and valeric acid (CAS 70693-33-3) was applied to five Wistar rats of each sex by dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15). Chromodacryorrhoea (nose), hunched posture and lethargy were noted among the animals. The animals had recovered from the symptoms by day 3. Erythema was were seen in the treated skin-area of one animal on day 3. No mortality occurred, body weights were within normal range and no abnormalities were found at a macroscopic level. The dermal LD50 value in Wistar rats was established to exceed 2000 mg/kg bw.

·              Isooctanoic acid, mixed tetraesters with pentaerythritol, 3,5,5-trimethylhexanoic acid and valeric acid (CAS 144911-11-9) was applied to the skin of to five Wistar rats of each sex by dermal application at 2000 mg/kg bodyweight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15). Hunched posture and/or chromodacryorrhoea were noted among all animals on day 2. In addition, maculate erythema or scales were seen on the treated skin site of one male and female between days 3 and 7. No mortality occurred, body weights were within normal range and no abnormalities were found at a macroscopic level. The dermal LD50 value in Wistar rats was established to exceed 2000 mg/kg bw.

·              Pentaerythritol mixed tetraesters with 2-ethylhexanoic acid, nananoic acid, and pentanoic acid (CAS 156559-00-1) was applied to the skin to five Wistar rats of each sex by dermal application at 2000mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of bodyweight. Macroscopic examination was performed after terminal sacrifice (day 15). All females and some males showed scales, scabs and/or general maculate erythema on the treated skin site during the observation period from day 3 onwards. In addition, chromodacryorrhoea was noted among some animals on days 1 and/or 2, with diarrhoea in one male between days 2 and 4. No mortality occurred, body weights were within normal range and no abnormalities were found at a macroscopic level. The oral LD50 value in Wistar rats was established to exceed 2000 mg/kg bw.

·              Reaction product of pentaerythritol and trimethylolpropane with n-pentanoic acid, 2-methylbutyric acid, n-heptanoic acid, 3,5,5-trimethylhexanoic acid, n-octanoic acid and n-decanoic acid, 2000 mg/kg bw was applied to the skin of Sprague-Dawley CD rats (male/female) and observed daily for 14 days. No mortality occurred, clinical signs were not present, no effect on body weight, no treatment related effects at macroscopic level. The oral LD50 value in Wistar rats was established to exceed 2000 mg/kg bw.

 

Four in vivo skin irritation studies have been conducted with read-across substances as detailed below:

·              Three rabbits were treated by dermal application of 0.5 ml of the Decanoic acid, mixed esters with octanoic acid, pentaerythritol and valeric acid (CAS 70693-33-3) for four hours using a semi-occlusive dressing, observations were then made at 1, 24, 48 and 72 hours after exposure. Very slight erythema in the treated skin-areas of all animals was noted, however this resolved within 1 day post exposure.

·              Isooctanoic acid, mixed tetraesters with pentaerythritol, 3,5,5-trimethylhexanoic acid and valeric acid (CAS 144911-11-9) was applied to three rabbits for four hours using a semi-occlusive dressing, observations were then made at 1, 24, 48 and 72 hours after exposure. Very slight erythema and/or very slight oedema in the treated skin-areas of the three rabbits. The skin Irritation had resolved within 24 hours in two animals and within 48 hours in the other animal.

·              Pentaerythritol mixed tetraesters with 2-ethylhexanoic acid, nananoic acid, and pentanoic acid (CAS 156559-00-1) were applied to the skin of three rabbits and observed at 1, 24, 48 and 72 hours after exposure. Four hours exposure to 0.5 ml of the test substance resulted in very slight erythema in the treated skin-areas of the three rabbits. The skin irritation had resolved within 24 hours after exposure in all animals.

·              Reaction product of pentaerythritol and trimethylolpropane with n-pentanoic acid, 2-methylbutyric acid, n-heptanoic acid, 3,5,5-trimethylhexanoic acid, n-octanoic acid and n-decanoic acid were applied to the skin of three rabbits, observations were made at 1, 24, 48 and 72 hours after exposure. 0.5mL resulted in very slight erythema was observed at two treated skin sites at 1h observation time. Very slight to well-defined erythema was noted at all treated skin sites at the 24 h observation time. Very slight erythema was noted at one treated skin site at 48 and 72 h observation time. Very slight oedema was noted at one treated skin site at the 1 and 24 h observation time. All treated skin sites appeared normal (effects on skin were completely reversible) at the 7-day observation.

 

Four in skin sensitisations studies have been conducted with read-across substances as detailed below:

·              The skin sensitisation potential of Decanoic acid, mixed esters with octanoic acid, pentaerythritol and valeric acid (CAS 70693-33-3); Isooctanoic acid, mixed tetraesters with pentaerythritol, 3,5,5-trimethylhexanoic acid and valeric acid (CAS 144911-11-9); Pentaerythritol mixed tetraesters with 2-ethylhexanoic acid, nananoic acid, and pentanoic acid (CAS 156559-00-1) was assessed using the mouse local lymph node assay (LLNA). Five experimental animals were epidermally exposed to a 5%, 50% and 100% concentration respectively on three consecutive days. The SI/DPM values indicated that the substances were not skin sensitisers.  

·              Guinea pig maximisation test was conducted on 20 guinea pigs with Reaction product of pentaerythritol and trimethylolpropane with n-pentanoic acid, 2-methylbutyric acid, n-heptanoic acid, 3,5,5-trimethylhexanoic acid, n-octanoic acid and n-decanoic acid to assess its skin sensitisation potential, with 10 guinea pigs serving as a control. Following Intradermal induction, very slight or well-defined erythema was noted at the intradermal induction sites of all test group animals at the 24 h observation and in nineteen test group animals at the 48 h observation. Very slight erythema was noted at the intradermal induction sites of all control group animals at the 24 and 48 h observations. Topical induction induced very slight or well-defined erythema and incidents of very slight oedema were noted at the induction sites of all test group animals at the 1 h observation with very slight erythema in ten test group animals at the 24 h observation. Bleeding from the intradermal induction sites of four test group animals was noted at the 1 h observation. Isolated incidents of small superficial scattered scabs or hardened dark brown/black-coloured scab were noted at the 24 h observation. Bleeding from the intradermal induction sites was noted in one control group animal at the 1 h observation. No signs of erythema or oedema were noted at the treatment sites of control group animals at the 1 and 24 h observations. No skin reactions were observed in any animal following topical challenge.

 

Four in repeated dose toxicity studies have been conducted with read-across substances as detailed below:

·              Decanoic acid, mixed esters with octanoic acid, pentaerythritol and valeric acid (CAS 70693-33-3). Based on the results of a 5-day range finding study, the dose levels for the 28-day toxicity study were selected to be 0, 50, 150 and 1000 mg/kg/day. The test substance was administered daily for 28 days by oral gavage to SPF-bred Wistar rats. One control group and three treated groups were tested, each consisting of 5 males and 5 females. There were no treatment-related effects noted at 50, 150 mg/kg/day. At1000 mg/kg/day, higher red blood cell count (female), lower cholesterol values (male) was noted, males were also seen to have enlarged livers at this dose. The effects however were not supported by other changes in the blood parameters or histopathological legions and as such were deemed not to be toxicologically relevant. It was concluded that the No Observed Adverse Effect Level (NOAEL) for the test substance was 150 mg/kg/day, based on the absence of functional or morphological disturbances supporting higher red blood cell count and lower cholesterol values in the high dose females and males respectively.

 

·              Pentaerythritol mixed tetraesters with 2-ethylhexanoic acid, nananoic acid, and pentanoic acid (CAS 156559-00-1)

Based on the results of a 5-day range finding study, the dose levels for the 28-day toxicity study were selected to be 0, 50, 150 and 1000 mg/kg/day. The test substance was administered daily for 28 days by oral gavage to SPF-bred Wistar rats. There were no treatment related effects noted and as such a NOAEL of 1000 mg/kg/day was established.

·              Isooctanoic acid, mixed tetraesters with pentaerythritol, 3,5,5-trimethylhexanoic acid and valeric acid (CAS 144971-11-9) Based on the results of a 5-day range finding study, the dose levels for the 28-day toxicity study were selected to be 0, 50, 150 and 1000 mg/kg/day. The test substance was administered daily for 28 days by oral gavage to SPF-bred Wistar rats. Treatment-related findings observed were as follows:

50 mg/kg/day:- Renal hyaline droplets (2/5 males), degeneration and/or necrosis of the tubular epithelium of the renal cortex (1/5 males).

150 mg/kg/day:- Renal hyaline droplets (all males), increased incidence and severity of tubular basophilia in the kidneys (2/5 males), degeneration and/or necrosis of the tubular epithelium of the renal cortex (4/5 males).

1000 mg/kg/day:- Slightly lower weight gain on day 8 (males). -increased absolute and relative food intake in weeks 1/2 (males). -Slightly increased red blood cell count and haematocrit levels (females). -increased liver weights and liver to bodyweight ratios (females). -Renal hyaline droplets: (all males), increased incidence and severity of tubular basophilia in the kidneys (3/5 males), degeneration and/or necrosis of the tubular epithelium of the renal cortex (all males).

No Observed Adverse Effect Level (NOAEL) could not be determined for males, but was established to be 150 mg/kg/day for females. However, since the male kidney findings are a species and sex specific response which is not observed in humans, a NOAEL of 150 mg/kg/day may be considered for both sexes.

 

·              Pentaerythritol ester of pentanoic acids and isononanoic acid

The 90-day study with pentaerythritol ester of pentanoic acids and isononanoic acid (CAS 146289-36-3) show the following effects: deposition of intracellular fat and fatty degeneration of the hepatocytes, the increased weights of the liver, both in female only, and the increased activity of alkaline phosphatase correlate with each other and identify the liver as the target organ. However these effects can be seen as adaptive response.

Except for the increased kidney weights in the males, all changes were no longer apparent at the end of the treatment-free period. The increased kidney weights were statistically significant only in the animals of the high dose group. The increase in kidney weights in all male animals could be correlated to the formation of hyaline droplets a phenomenon widely accepted to be specific to the male rat and as such considered to have no relevance to man. The results indicate that the NOAEL was 300 mg/kg bw day.

·              Reaction product of pentaerythritol and trimethylolpropane with n-pentanoic acid, 2-methylbutyric acid, n-heptanoic acid, 3,5,5-trimethylhexanoic acid, n-octanoic acid and n-decanoic acid.

One 28- day study conducted with the test substance showed no signs of overt toxicity except for treatment-related kidney changes. Globular accumulations of eosinophilic material were observed in the renal proximal tubular epithelium of males treated at 1000, 500 or 150 mg/kg bw/day. The presence of globular accumulations of eosinophilic material in the tubular epithelium is consistent with the appearance of hydrocarbon nephropathy which results from the excessive accumulation of alpha2-microglobulin in renal proximal tubular epithelial cells. Alpha2-microglobulin is found only in the proximal tubular epithelium of adult male rats, this condition does not, therefore, represent a hazard to human health. All remaining morphological changes were those commonly observed in laboratory maintained rats of the age and strain employed, and there were no differences in incidence or severity between control and treatment groups that were considered to be of toxicological significance. For females, treatment related effects were observed at 1000 mg/kg bw/day. A clear NOAEL for males was not obtained, while the NOAEL for females was considered to be 500 mg/kg bw/day. 

 

Under the conditions of an Ames test, the following substances were not mutagenic with and without metabolic activation. Decanoic acid, mixed esters with octanoic acid, pentaerythritol and valeric acid (CAS 70693-33-3), Pentaerythritol mixed tetraesters with 2-ethylhexanoic acid, nananoic acid, and pentanoic acid (CAS 156559-00-1), Isooctanoic acid, mixed tetraesters with pentaerythritol, 3,5,5-trimethylhexanoic acid and valeric acid (CAS 144971-11-9), Pentaerythritol tetraesters of n-C5, n-C7, n-C8, i-C9 and n-C10 fatty acids and Reaction product of pentaerythritol and trimethololpropane with n-pentanoic acid, 2-methylbutyric acid, n-heptanoic acid, 3,5,5-trimethylhexanoic acid, n-octanoic acid and n-decanoic acid.

An in vitro mammalian chromosome aberration using human lyphocytes with test substances Pentaerythritol mixed tetraesters with 2-ethylhexanoic acid, nananoic acid, and pentanoic acid (CAS 156559-00-1), Isooctanoic acid, mixed tetraesters with pentaerythritol, 3,5,5-trimethylhexanoic acid and valeric acid (CAS 144971-11-9) and Decanoic acid, mixed esters with octanoic acid, pentaerythritol and valeric acid (CAS 70693-33-3) were negative, with and without metabolic activation.

In vitro gene mutation study in mammalian cells mouse lymphoma L5178Y cells using Reaction product of pentanoic acid, C6-C12 mixed fatty acids, pentaerythritol, heptanoic acid and 3,5,5-trimethylhexanoic acid (CAS 156558-98-4) did not induce mutations with and without metabolic activation.

 

Oral gavage administration of Reaction product of pentanoic acid, C6-C12 mixed fatty acids, pentaerythritol, heptanoic acid and 3,5,5-trimethylhexanoic acid (CAS 156558-98-4) at 100, 300 and 1000 mg/kg was administered to rats from implantation through the end of gestation. Parental toxicity was noted at 300 and 1000 mg/kg. Pale discoloured kidneys recorded at necropsy for one male at 300 mg/kg and five males at 1000 mg/kg showed slight-moderate hyaline droplet accumulation, which was the microscopic correlate to this finding. These hyaline droplets were considered to represent alpha2μglobulin, a normal protein in male rats which undergoes re-absorption in the proximal cortical tubules. A range of chemicals are known to increase hyaline droplet formation leading ultimately to proximal cortical tubule cell injury, the formation of granular casts and increased cell turnover as manifest by tubular basophilia. This protein is not present in female rats nor in higher mammals, including man. Therefore, these findings are not predictive for man and their occurrence has no relevance in human safety assessment. No reproduction and developmental toxicity was observed up to the highest dose level tested (1000 mg/kg).

2,2-bis[(octanoyloxy)methyl]butyl decanoate (CAS 11138-60-6) was tested in a prenatal developmental toxicity study. The test substance was percutaneously applied to Sprague-Dawley rats for 6 h/day under occlusive conditions. 25 animals per sex per dose were treated with 200, 600 or 2000 mg/kg bw/day in corn oil on Days 6-15 of gestation. Control animals (25 per sex per dose) received the vehicle. The middle and the high dose levels caused some local irritation at the site of application, but no decreases in maternal weight gain or food consumption. There were no differences from control in any of the developmental parameters measured, including embryo/fetal viability, fetal weight, malformations, or variations. Therefore, a NOAEL >=2000 mg/kg bw/day was derived for prenatal development and for systemic maternal toxicity. Due to the irritation effects on skin, the local maternal NOAEL was found to be 200 mg/kg bw/day.

 

Toxicokinetic parameters

Absorption

Oral

The acute oral toxicity studies that were conducted on the read across structural analogues did not reveal any signification effects, with animals showing signs of hunched posture and piloerection, effects however were see to be reversible within 24-72 hours. Repeated dose studies provided evidence that the polyol esters induce treatment related effects associated with hydrocarbon neuropathy; which is not toxicologically relevant to humans. This suggests that the bioavailability of the substances might be relatively high.

The test substance is seen to have a low waters solubility based on the read-across substances with a mean value of 8.5E^-4mg/L at 20 °C and a log Kow of 9.18. The absorption of highly lipophilic substances (log Kow ≥ 4) may be limited by the inability of such substances to dissolve in gastrointestinal fluids and therefore make contact with the mucosal surface. However, the absorption of such substances will be increased if they undergo micellular solubilisation by bile salts. As a worst case, for risk assessment purposes the oral absorption of the test substance is set at 100%.

 

Dermal

The results from dermal studies including the acute/repeated dose dermal toxicity study, in vivo skin irritation studies and the GPMT study do not provide much evidence to support significant skin absorption. Very slight erythema/oedema being the most notable effect induce by the read-across substances, however these effects were seen to be reversible within 24 to 48 hours. The log Kow value of the test substance is assumed to be > 69.8 therefore the dermal absorption of the substance is expected to be limited based on the high log Kow value. At log Kow values above 6, the rate of transfer between the stratum corneum and the epidermis will be slow and will limit absorption across the skin and uptake into the stratum corneum itself may be slow. Maximum dermal absorption is often associated with values of log Kow between +1 and +2 (ECETOC (European Centre for Ecotoxicology and Toxicology of Chemicals). Monograph No, 20; Percutaneous absorption. August 1993). In addition, the substance must be sufficiently soluble in water to partition from the stratum corneum into the epidermis. The test substance has an estimated water solubility of 8.5E^-4mg/L at 20 °C therefore dermal uptake is likely to be low. In conclusion, dermal absorption of the test substance is expected to be low. However, as a worst case, for risk assessment purposes the dermal absorption of the test substance is set at 100%.

 

 

Inhalation

Currently there are no studies associated Reaction product of pentanoic acid, C6-C12 mixed fatty acids, pentaerythritol, heptanoic acid and 3,5,5-trimethylhexanoic acid that were conducted via the inhalatory route. The substance has a low vapour pressure (0.003 Pa at 20 °C) therefore a significant inhalation exposure to vapours is not expected. Moderate log Kow values (between -1 and 4) are favourable for absorption directly across the respiratory tract epithelium by passive diffusion. The test substance has a high log Kow value (> 9.18) therefore it may be taken up by micellular solubilisation particularly as the substance is poorly soluble in water (8.5E^-4mg/L at 20 °C). As a worst case, for risk assessment purposes the inhalation absorption of the test substance is set at 100%.

 

Distribution

In the repeated dose toxicity studies and reproductive/developmental studies with read-across substances,minor treatment related effects on the clinical pathology parameters were observed, indicating distribution throughout the body. The test substance based on the information provided by the read-across substances is epis lipophilic therefore it is likely to distribute into cells and the intracellular concentration may be higher than extracellular concentration particularly in fatty tissues. Short chain fatty acids released following hydrolysis of the test substance in the gastrointestinal tract are likely to be widely distributed in the body. Substances with high log Kow values tend to have longer half-lives unless their large volume of distribution is counterbalanced by a high clearance. There is the potential for highly lipophilic substances to accumulate in individuals that are frequently exposed to that substance. Once exposure stops, the concentration within the body will decline at a rate determined by the half-life of the substance. However, as detailed below, the test substance is likely to undergo rapid hydrolysis following absorption so only low and transient exposure to the parent compound is expected.

 

Metabolism and excretion

The ester groups in the test substance are likely to undergo lipase-catalysed hydrolysis in the gastrointestinal tract, releasing fatty acids and pentaerythritolso only low and transient exposure to the parent compound is expected. Following absorption, the fatty acids are transported to the tissues of the body including the liver where they undergo oxidation in the cells to carbon dioxide, acetate and ketones. Fatty acids are transported across the outer mitochondrial membrane by carnitine acyl transferases. Once inside the mitochondrial matrix, the fatty acyl-carnitine reacts with coenzyme A to release the fatty acid and produce acetyl-CoA. Fatty acids then undergo β-oxidation. During this process, two-carbon molecules acetyl-CoA are repeatedly cleaved from the fatty acid. Acetyl-CoA can then enter the citric acid cycle (Krebs cycle), which produces NADH and FADH2. NADH and FADH2 are subsequently used in the electron transport chain to produce ATP, the energy currency of the cell. Pentaerythritol is water soluble therefore it is most probably excreted in the urine unchanged or in conjugated form.

 

By read-across from the mutagenicity assays it appears that the substance would not metabolised toward genotoxic structures.

 

Conclusion

In conclusion, there is no evidence that would suggest that Reaction product of pentanoic acid, C6-C12 mixed fatty acids, pentaerythritol, heptanoic acid and 3,5,5-trimethylhexanoic acid is significantly absorbed via the dermal route and the inhalation route. The results of an oral repeated dose toxicity study indicate that the substance may be absorbed orally in the rat. It is likely that the ester groups of the test substance would undergo lipase-catalysed hydrolysis in the gastrointestinal tract, releasing fatty acids. Following absorption, the fatty acids are transported to the tissues of the body including the liver where they undergo oxidation in the cells. Pentaerythritol is water soluble therefore it is most probably excreted in the urine unchanged or in conjugated form

Consequently, the substance is considered to have low bioaccumulation potential.

 

 

Applicant's summary and conclusion

Conclusions:

In conclusion, there is no evidence that would suggest that Reaction product of pentanoic acid, C6-C12 mixed fatty acids, pentaerythritol, heptanoic acid and 3,5,5-trimethylhexanoic acid is significantly absorbed via the dermal route and the inhalation route. The results of an oral repeated dose toxicity study indicate that the substance may be absorbed orally in the rat. It is likely that the ester groups of the test substance would undergo lipase-catalysed hydrolysis in the gastrointestinal tract, releasing fatty acids. Following absorption, the fatty acids are transported to the tissues of the body including the liver where they undergo oxidation in the cells. Pentaerythritol is water soluble therefore it is most probably excreted in the urine unchanged or in conjugated form
Consequently, the substance is considered to have low bioaccumulation potential.