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Administrative data

Description of key information

Repeated dose toxicity: Oral NOAEL (rat, m/f): >= 1000 mg/kg bw/day (OECD 407, GLP, analogue approach)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2, due to read across) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common origin, common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to endpoint discussion for further details). The selected studies are thus sufficient to fulfil the standard information requirements set out in Annex VIII, 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

Mode of Action Analysis / Human Relevance Framework

Additional information

Justification for grouping of substances and read-across

There are no data available for repeated dose toxicity of 1,3-Propanediol, 2,2-dimethyl-, C5-9 carboxylates (CAS 85711-80-4). In order to fulfil the standard information requirements set out in Annex VIII, 8.6, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006 whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity, the substances Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids (CAS 68424-31-7), Fatty acids, C7-8, triesters with trimethylolpropane (CAS 189120-64-7) and 3,5,5-trimethylhexanoic acid mixed tetraesters with pentaerythritol and valeric acid (CAS 131459-39-7) are selected as source substances for hazard assessment. 

Repeated dose toxicity: oral

Since no studies investigating the repeated dose toxicity of 1,3-Propanediol, 2,2-dimethyl-, C5-9 carboxylates (CAS 85711-80-4) are available, in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5, read-across from the structurally related analogue substances Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids (CAS 68424-31-7), Fatty acids, C7-8, triesters with trimethylolpropane (CAS 189120-64-7) and 3,5,5-trimethylhexanoic acid mixed tetraesters with pentaerythritol and valeric acid (CAS 131459-39-7) was conducted.

CAS 131459-39-7

A repeated dose toxicity study was conducted according similar to OECD Guideline 407 and GLP with 3,5,5-trimethylhexanoic acid mixed tetraesters with PE and valeric acid, CAS 131459-39-7 (Jones, 1999). The test substance was administered to 5 animals per sex in arachis oil by gavage in concentrations of 15, 150 and 1000 mg/kg bw/day for 28 consecutive days.

No mortalities were observed. An incidence of increased salivation was detected around the time and up to five hours after dosing in high-dose animals from Day 14 onwards. Sporadic incidents of diuresis, red/brown staining of the ano-genital region and wet fur were also detected at this dose level.

No adverse effects on body weight development and dietary intake were detected. However, a slight increase in water consumption for animals of either sex treated with 1000 mg/kg bw/day was detected during the latest week of the study. With regard to organ weight, males treated with 1000 mg/kg bw/day showed a statistically significant increase in relative kidney weight whereas females from this treatment group showed increased in relative liver weights when compared with controls. No treatment-related adverse effects were detected among animals of either sex treated with 150 or 15 mg/kg bw/day. All males treated with 1000 mg/kg bw/day showed speckled kidneys at terminal kill whilst one female from this treatment group showed pallor of the liver with accentuated lobular pattern. No treatment-related macroscopic abnormalities were observed in the other groups.

The liver changes identified during the study are generally considered to be adaptive in nature whilst the kidney changes are consistent with well documented changes that are peculiar to the male rat in response to treatment with some hydrocarbons. Therefore, these effects are not considered as adverse and hence, a NOAEL ≥ 1000 mg/kg bw/day was defined for both sexes.

CAS 68424-31-7

A 28 day study was conducted according to OECD Guideline 407 with Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids (CAS 68424-31-7) (Brammer, 1993). The test substance was administered in concentrations of 1000 ppm, 5000 ppm, 12500 ppm resembling 112, 562 and 1450 mg/kg bw/day for male and 119, 586 and 1613 mg/kg bw/day for female rats, respectively to 5 animals per sex and dose for 28 consecutive days.

There were no toxicologically significant effects on body weight, food consumption and clinical condition up to and including the highest dose level. Changes in some 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. There were no clinical signs indicative of neurological changes in the brains of the 12500 ppm group. A minimal hepatocyte hypertrophy, present in males in the 12500 ppm group, is 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/day could be identified for male and female rats, respectively.

CAS 189120-64-7

A 28-day oral feeding toxicity study with Fatty acids, C7-8, triesters with trimethylolpropane (CAS 189120-64-7) was performed according to OECD Guideline 407 and under GLP conditions (Trimmer, 2000). Groups of 5 male and 5 female Cr:CD BR rats were exposed to the substance at 100, 300 and 1000 mg/kg bw/day by gavage, 7 days/week for 28 days. Control animals (5 per sex and dose) received the concurrent vehicle, peanut oil. Observations and examinations of the animals included clinical signs, body weight, food consumption, haematology, clinical chemistry, organ weights, neurobehaviour, gross necropsy and histopathology. Female animals tolerated the daily oral administration of the test substance without any adverse effects (included mortality) up to the high dose of 1000 mg/kg bw/day. In male animals no adverse effects were observed for all investigated parameters except for histopathology. An increased amount of hyaline droplets (the main constituent of which is alpha-2µ-globulin) in the proximal cortical tubular epithelium was confirmed microscopically in the cytoplasm of the renal cortical tubular epithelial cells in male rats treated with 300 and 1000 mg/kg bw/day, respectively. As this phenomenon is widely accepted to be specific to the male rat and as such is considered to have no relevance to man, the 28-day oral NOAEL, for Fatty acids, C7-8, triesters with trimethylolpropane was found 1000 mg/kg bw/day for male and female rats

Conclusion for Repeated Dose Toxicity – Oral

Following a weight-of-evidence approach based on data available for structural analogue substances, the target substance 1,3-Propanediol, 2,2-dimethyl-, C5-9 carboxylates (CAS 85711-80-4) is not considered as hazardous after repeated expsoures.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Hazard assessment is conducted by means of read-across from structural analogues. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Justification for classification or non-classification

Based on read-across from structurally similar substances, the available data on repeated dose toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.