Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

The hazard assessment is based on the data currently available. New studies with the registered substance and/or other member substances of the polyol esters category will be conducted in the future. The finalised studies will be included in the technical dossier as soon as they become available and the hazard assessment will be re-evaluated accordingly.


For further details, please refer to the category concept document attached to the category object (linked under IUCLID section 0.2) showing an overview of the strategy for all substances within the polyol esters category.


 


Oral (OECD 407, GLP, rat): NOAEL ≥ 1000 mg/kg bw/day


Read-across from structural analogue source substances Dipentaerythritol hexaesters with fatty acids, C5 and C9iso (CAS No. 647028-25-9), Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids (CAS No. 68424-31-7), and Fatty acids, C8-10 mixed esters with dipenaterythritol, isooctanoic acid, pentaerythritol and tripentaerythritol (CAS No. 189200-42-8)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
Summary of available data used for the endpoint assessment of the target substance
Adequacy of study:
weight of evidence
Justification for type of information:
Please refer to the Analogue Approach Justification provided in Section 13.
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
Key result
Dose descriptor:
NOAEL
Effect level:
>= 1 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: overall effects, NOAEL corresponding to the highest dose tested
Remarks on result:
other: Source: CAS No. 146289-36-3, Emery, 1998
Key result
Critical effects observed:
no

Additional studies and results taken into account by Weight-of-Evidence:


CAS No. 647028-25-9, Safepharm, 2000: NOAEL (rat, m/f) >= 1000 mg/kg bw/day (highest dose tested)


CAS No. 68424-31-7, Zeneca Central Toxicology, 1993: NOAEL (rat, female, 28d) = 1613 mg/kg bw/day (highest dose tested); NOAEL (rat, male, 28d) = 1450 mg/kg bw/day (highest dose tested)


CAS No. 189200-42-8, Exxon, 1995d: NOAEL (rat, m/f, 28d) NOAEL (rat, m/f, 28d) ≥ 1000 mg/kg bw/day (highest dose tested)

Conclusions:
Oral exposure of male and female rats to the test substances either in the diet or by gavage for 28 days did not yield any adverse effects and hence resulted in NOAEL values of ≥ 1000 mg/kg bw/day, corresponding to the highest doses tested.
Executive summary:

The oral repeated dose toxicity of the target substance is estimated based on adequate and reliable short-term (28-day) oral toxicity studies of structural analogue source substances. Oral exposure of male and female rats to the test substances either in the diet or by gavage for 28 days did not yield any adverse effects and hence resulted in NOAEL values of ≥ 1000 mg/kg bw/day, corresponding to the highest doses tested. Based on these findings, a NOAEL for repeated dose toxicity after oral exposure of ≥ 1000 mg/kg bw/day is also identified for the target substance. As explained in the analogue justification, the differences in molecular structure between the target and the source substances are unlikely to lead to differences in oral repeated dose toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
The available information comprise adequate and reliable (Klimisch score 1 and 2) studies from various source substances with similar structures and intrinsic properties. Read-across is justified based on common precursors and hydrolysis products and consistent trends in environmental fate, ecotoxicological and toxicological profile. The selected studies are thus sufficient to fulfil the standard information requirements set out in Annexes VIII - X, 8.6, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The hazard assessment is based on the data currently available. New studies with the registered substance and/or other member substances of the polyol esters category will be conducted in the future. The finalised studies will be included in the technical dossier as soon as they become available and the hazard assessment will be re-evaluated accordingly.


For further details, please refer to the category concept document attached to the category object (linked under IUCLID section 0.2) showing an overview of the strategy for all substances within the polyol esters category.


 


Oral repeated dose toxicity


There are several short-term repeated dose toxicity studies available for structural analogue source substances investigating the toxicity after oral exposure. All studies are accounted for by means of a Weight-of-Evidence approach.


 


A 90-day oral toxicity study with Pentaerythritol ester of pentanoic acids and isononanoic acid (CAS 146289-36-3) was performed according to OECD Guideline 408 and under GLP conditions (Emery, 1998). Groups of 10 male and 10 female Wistar rats were exposed to the substance at 100, 300 and 1000 mg/kg bw/day by gavage daily, 7 days/week for 90 days. Satellite control and high dose groups containing 10 male and female animals each were observed for additional 28 days. Control animals (10 per sex and dose) received the concurrent vehicle, distilled water containing 1% Tween 80. Observations and examinations of the animals included clinical signs, body weight, food consumption, haematology, clinical chemistry, organ weights, neurobehaviour, gross necropsy and histopathology. The daily oral administration of the test substance was tolerated without any adverse effects up to 1000 mg/kg bw/day. No mortality was observed except for two animals that died shortly after administration due to incorrect gavage. Absolute and relative kidney weights were increased in all male animals in the high dose group which was still present after the recovery period. However, histopathology revealed no adverse effects in the kidney. Absolute and relative liver weights were increased in both sexes but this was no longer apparent after the recovery period in females. Other significant differences seem to be incidental. The activity of alkaline phosphatase of the serum significantly increased in the high dose group, males and females. This indicates damage to liver cells and/or an increased function rate. This finding was no longer apparent at the end of the treatment-free period. Except for the increased kidney weights and liver weight in the males, all changes (e.g. clinical chemical changes) were no longer apparent at the end of the treatment-free period. 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. A 90-day oral NOAEL of 1000 mg/kg bw/day was found for Pentaerythritol ester of pentanoic acids and isononanoic acid in male and female rats.


 


The short-term (28-day) repeated dose toxicity of Dipentaerythritol hexaesters with fatty acids, C5 and C9iso (CAS No. 647028-25-9) was assessed in a study performed according to OECD Guideline 407 and in compliance with GLP provisions (WoE, RA-A, 647028-25-9, 2000a). Groups of 5 male and 5 female Crl:CD BR rats were dosed once daily, 7 day/week, with 150, 500 and 1000 mg/kg bw/day of the test substance by oral gavage for 28 consecutive days. The animals of a control group received only the vehicle arachis oil. No mortality occurred during the study period and no clinical signs of toxicity were observed in test or control animals throughout the study. Minor effects observed, e.g. fur loss in one female of the highest dose group, were considered incidental. No adverse effect on body weight was noted. Nevertheless, a statistically significant reduction in body weight gain was apparent for 1000 and 500 mg/kg/day males during week 1 of the study. The dose relationship was not credible and the intergroup differences were considered to be a result of slightly higher than usual control group body weights gains. No treatment-related changes in the hematological parameters were measured. No treatment-related effect on organ weights was noted. Males treated with 500 mg/kg/day showed a statistically significant reduction in absolute epididymides weight when compared with control animals but, in the absence of a convincing dose-response relationship, the intergroup difference was considered to be incidental and of no toxicological importance. Necropsy revealed no substance-related findings. Three males treated with 1000 mg/kg/day demonstrated globular accumulations of eosinophilic material in the proximal tubular epithelium which could be regarded as a possible effect of treatment. The authors considered this finding consistent with the appearance of hydrocarbon nephropathy, which results from the excessive accumulation of α2-microglobulin in renal proximal tubular epithelium of adult male rats, which does not represent a hazard to human health. Taken all observations in consideration, the oral NOAEL value was therefore determined to be ≥ 1000 mg/kg bw/day, corresponding to the highest dose tested.


 


In a short-term (28 day) repeated dose toxicity study Fatty acids, C5-10, esters with pentaerythritol (CAS No. 68424-31-7) was investigated according to OECD Guideline 407 and under GLP conditions (WoE, RA-A, 68424-31-7, 1993). The test substance was administered in the diet in concentrations of 1000 ppm, 5000 ppm and 12500 ppm (corresponding to 112, 562 and 1450 mg/kg bw/day for male and 119, 586 and 1613 mg/kg bw/day for female rats) to 5 Alpk:APfSD rats per sex and dose for 28 consecutive days. Control animals (5 per sex and dose) received the plain diet. There were no toxicologically significant effects on body weight, food consumption and clinical condition and mortality up to and including the highest dose level. Changes in clinical chemistry and red cell-related parameters were observed in male rats at 12500 ppm, but these were minor and considered not to be of toxicological significance. A minimal hepatocyte hypertrophy present in males of the 12500 ppm group was observed and considered to be evidence of an adaptive response. Microscopic examination of the kidneys from male animals from all dose groups revealed an increase in hyaline droplet formation (the main constituent of which is alpha-2µ-globulin) and tubular basophilia. This phenomenon is widely accepted to be specific to the male rat and as such is considered to have no relevance to man. A NOAEL of 1450 and 1613 mg/kg bw/day could be identified for male and female rats, respectively.


 


In another 28-day subacute repeated dose toxicity study performed with Fatty acids, C8-10 mixed esters with dipenaterythritol, isooctanoic acid, pentaerythritol and tripentaerythritol (CAS No. 189200-42-8) equivalent or similar to OECD Guideline 407 under GLP conditions, male and female Crl:CD BR rats were dosed with 100, 500 and 1000 mg/kg bw/day by oral gavage once daily, 7 day/week for a total of 28 days (Exxon, 1995d). 5 animals per dose and sex were used. A control group receiving the vehicle polyethylene glycol (PEG 400) only was also included in the study design. One male animal of the 500 mg/kg bw group died after the first application due to a gavage error. This animal was replaced on day 1 with another animal that received one dose less than the other animals. All animals survived the study period until scheduled termination. No clinical signs occurred that were judged to be treatment-related, no effects on body weights and on food consumption of the treated animals were observed. Moreover, there were no significant differences in the hematology parameters between the negative control and the animals treated. There were also no significant differences in the clinical chemistry parameters which were judged to be test substance related. Neuro-behavioural observations made on day 8 and day 27 were unremarkable. The necropsy revealed no treatment-related findings. Single effects were observed but were considered to be incidental and not treatment-related. No significant differences in mean absolute organ weight and no histopathologic changes were observed in any of the organs or tissues examined between the test substance treated and negative control animals. In the mid dose group, there was a statistically significant increase in the mean relative testes weight. Due to the absence of a dose-response pattern, this effect was judged to be incidental. The oral NOAEL was therefore determined to be ≥ 1000 mg/kg bw/day.


 


Conclusion on repeated dose toxicity


In conclusion, the available studies clearly indicate a very low level of repeated dose toxicity after oral exposure. Since no toxicologically relevant findings were detected in any of the studies and hence all NOAELs determined correspond to the highest doses tested, no hazard with respect to oral repeated dose toxicity is identified for the target substance Octadecanoic acid, 1,1'-[2-[[3-[(1-oxooctadecyl)oxy]-2,2-bis[[(1-oxooctadecyl)oxy]methyl]propoxy]methyl]-2-[[(1-oxooctadecyl)oxy]methyl]-1,3-propanediyl] ester (CAS No. 70967-57-2) and a NOAEL of ≥ 1000 mg/kg bw/day is used for risk assessment and C&L purposes of the target substance.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 information on intrinsic properties of substances may be generated by means other than tests, e.g. using information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the read-across concept is applied to the target substance Octadecanoic acid, 1,1'-[2-[[3-[(1-oxooctadecyl)oxy]-2,2-bis[[(1-oxooctadecyl)oxy]methyl]propoxy]methyl]-2-[[(1-oxooctadecyl)oxy]methyl]-1,3-propanediyl] ester (CAS No. 70967-57-2), data gaps can be filled by interpolation from representative structural analogue source substances to avoid unnecessary animal testing.

The read-across concept is also used to derive the classification of the target substance taking the properties of the source substances into account. Based on the read-across concept, all available data on repeated dose toxicity do not meet the classification criteria according to Regulation (EC) No. 1272/2008 (CLP) and are therefore conclusive but not sufficient for classification.