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Administrative data

Description of key information

Acute toxicity: Oral LD50 (rat, m/f): > 2000 mg/kg bw (OECD 401, 423, and 425, GLP, analogue approach)
Acute toxicity: Dermal LD50 (rat, m/f): > 2000 mg/kg bw (OECD 402, GLP, analogue approach)
Acute toxicity: Inhalation LC50 (rat, m/f): > 4.06, 5.1 and 5.5 mg/mL (OECD 403, GLP, analogue approach)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2) 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).
Taken together, the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006. Therefore, the available information as a whole is sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2) 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).
Taken together, the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006. Therefore, the available information as a whole is sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP-guideline study with acceptable restrictions. (Lack of data on test material.)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted in 1987
Deviations:
yes
Remarks:
(no data on test substance purity)
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
adopted in1992
Deviations:
yes
Remarks:
(no data on test substance purity)
Qualifier:
equivalent or similar to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
adopted in 1998
Deviations:
yes
Remarks:
(no data on test substance purity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan
- Age at study initiation: 9 - 10 weeks
- Weight at study initiation: 247 - 253 g (males), 217 - 239 g (females)
- Housing: animals were group housed by sex upon receipt and individually housed upon assignment to study in compliance with the National Research Council " Guide for the Care and Use of Laboratory Animals".
- Diet: Harlan Teklad Rodent Diet, ad libitum
- Water: Tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 22
- Humidity (%): 23 - 59
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
From: 9 Jan 2006
To: 23 Jan 2006
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: clipped skin of the dorsal area of the trunk
- Type of wrap if used: the treated skin site was covered with a gauze patch/dental dam, wrapped with an elastic bandage and secured with non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test substance was removed with water
- Time after start of exposure: 24 h
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were recorded immediately after dosing and at approximately 1, 2.5 and 4 h after dosing and daily thereafter through Day 15. Animals were weighed prior to dosing on Day 1 and on Days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: Mortality/morbidity (twice daily)
Statistics:
Body weights were summarized using descriptive statistics (mean and standard deviation).
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
No clinical signs of toxicity were observed up to the end of the 14-day observation period.
Body weight:
Body weight gains of all animals were withinthe normal ranges during the whole study period.
Gross pathology:
Necropsy revealed no substance-related findings.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
EU: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, a reliable (Klimisch score 2) study 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).
Taken together, the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006. Therefore, the available information as a whole is sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Additional information

Justification for grouping of substances and read-across

There are no data available for the acute toxicity of 2,2-bis[[(1-oxoheptyl)oxy]methyl]propane-1,3-diyl bisheptanoate (CAS 25811-35-2). In order to fulfil the standard information requirements set out in Annex VIII, 8.5 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 put 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 substance listed below are selected as reference substances for hazard assessment.

Overview of acute toxicity

CAS

Acute toxicity oral

Acute toxicity inhalation

Acute toxicity dermal

25811-35-2

Target substance

RA: CAS 67762-53-2

RA: CAS 71010-76-9

RA: CAS 68424-31-7

RA: CAS 68424-31-7

RA: CAS 67762-53-2

RA: CAS 71010-76-9

 

71010-76-9

LD 50 > 2000 mg/kg bw

--

LD50 > 2000 mg/kg bw

 68424-31-7

LD50 > 2000 mg/kg bw

LC50 > 5.1 mg/L (analytical concentration, highest testable concentration)

--

67762-53-2

LD50 > 2000 mg/kg bw

LC50 > 5.5 mg/L

--

 

The above mentioned substances are considered to be similar on the basis of structural similarity resulting in similar properties and/or activities. The available endpoint information is used to predict the same endpoints for of 2,2-bis[[(1-oxoheptyl)oxy]methyl]propane-1,3-diyl bisheptanoate (CAS 25811-35-2). A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Acute toxicity: oral

CAS 67762-53-2

The acute toxicity via the oral route of Fatty acids, C5-9 tetraesters with pentaerythritol has been investigated in two studies with rats (CAS 67762-53-2).

An acute oral toxicity study (limit test) was performed according to OECD Guideline 420 (fixed dose procedure) (Zolyniene, 1999). Groups of 5 males and females fasted CD Sprague-Dawley rats received single oral gavage doses of 2000 mg/kg bw. The animals were observed for 14 days following administration. No mortalities occurred. One animal showed alopecia extremities on snout which was not considered treatment related. No further clinical signs of toxicity were reported. No effect on body weight was noted. Finally necropsy revealed no substance-related findings. Thus, the acute oral LD50 was found to be greater than 2000 mg/kg bw.

Another acute oral toxicity study (limit test) was performed comparable to OECD Guideline 401 (D’Aleo, 1984). The test substance was administered by gavage at a concentration of 15000 mg/kg bw to groups of 5 male and female Sprague-Dawley rats. The animals were observed for 14 days following administration. No mortalities occurred. All animals exhibited clear, oily perineal staining on the 1st, 2nd, and 3rd day following treatment. This condition normally regarded as an adverse effect, was considered to be a consequence of the high dose level administered and not considered a toxic sign. No further clinical signs of toxicity were reported. The acute oral LD50 was found to be greater than 15000 mg/kg bw.

In summary, the oral LD50 of Fatty acids, C5-9 tetraesters with pentaerythritol is greater than 2000 mg/kg bw.

 

CAS 68424-31-7

The study conducted with Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids (CAS 68424-31-7) (Robinson, 1991) with limitations (reduced animal number), revealed no mortality and no other toxic effects, but an initial weight loss after treatment of rats with 2000 mg/kg bw. However this effect was completely reversible and the animals showed subsequently normal body weight gain.

 

CAS 71010-76-9

An acute oral toxicity study with Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid (CAS 71010-76-9) was performed according to OECD Guideline 425 (up and down procedure, limit test) and GLP (Mallory, 2006). Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid was administered by gavage to one female Sprague-Dawley rat at the starting dose of 2000 mg/kg bw. Since no mortality and no other toxic effects could be detected during the 14 day study period, 4 further female animals were equally dosed with 2000 mg/kg bw. No clinical signs of toxicity were observed up to the end of the 14-day observation period. No effect on body weight was noted. Finally, necropsy revealed non substance-related findings. The oral LD50 value in female rats was found to exceed 2000 mg/kg bw.

Acute toxicity: inhalation

CAS 68424-31-7

An acute inhalation toxicity study was performed with Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids (CAS 68424-31-7) comparable to OECD Guideline 403. 5 male and female Alpk:APfSD rats were exposed for 4 hours to 5.1 mg/L test substance aerosol by nose only inhalation (Parr-Dobrzanski, 1994). The test substance caused no mortality, body weight changes or abnormalities in necropsy during the 15 day study period. Some clinical signs were noticed, which consisted of hunched position, chromodacryorrhea, piloerection, staining around nose and wet fur. These signs however occurred during or just after exposure and were clearly consistent with the use of restraint for exposure. The LC50 was therefore found to be greater than 5.1 mg/L.

 

CAS 67762-53-2

The acute toxicity via the inhalation route of Fatty acids, C5-9 tetraesters with pentaerythritol has been investigated in rats in two studies (CAS 67762-53-2).

The first study was conducted comparable to OECD Guideline 403 and according to GLP. 10 male and female Sprague-Dawley rats were exposed for 4 hours to 0.48 or 4.06 mg/L test substance aerosol by whole body inhalation exposure (Mekitarin, 1990). No mortality, clinical signs, body weight changes or abnormalities in necropsy were observed during the 15 day study period in any group. The LC50 was therefore found to be greater than 4.06 mg/L.

In the second study 10 male and 5 female CD Sprague-Dawley rats were exposed for 4 hours to 5.5 mg/L test substance aerosol by nose/head only inhalation (Hoffman, 1999). No mortalities occurred during the study period. Nasal discharge was noted as the only sign of clinical toxicity. The test group females lost weight during the first week after the test material exposure, but gained weight during the second week after exposure. In all other animals no effect on body weight was noted. Necropsy examination revealed no substance-related findings. The LC50 was therefore found to be greater than 5.5 mg/L.

In summary, the LC50 of Fatty acids, C5-9 tetraesters with pentaerythritol is greater than 5.5 mg/L.

Acute toxicity: dermal

CAS 71010-76-9

An acute dermal toxicity study (limit test) was performed on Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid (CAS 71010-76-9) comparable to OECD Guideline 402 and GLP (Mallory, 2006). 5 male and female Sprague-Dawley rats were exposed to 2000 mg test substance /kg bodyweight for 24 hours on the back skin under semiocclusive conditions. The observation period was 14 days. No clinical signs of systemic toxicity were noted in any animal during the study period. Body weight gain and necropsy at study termination revealed no abnormalities. Thus, the acute dermal LD50 in rats for Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid was found to exceed 2000 mg/kg bw.

Conclusion for acute toxicity

In summary, for acute oral toxicity studies from Fatty acids, C5-9 tetraesters with pentaerythritol has been investigated in two studies with rats (CAS No. 67762-53-2), Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids (CAS 68424-31-7) and, Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid (CAS 71010-76-9) are available and resulted in oral LD50 values > 2000 mg/kg bw.

For acute inhalation toxicity, studies with Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids (CAS 68424-31-7), and Fatty acids, C5-9 tetraesters with pentaerythritol has been investigated in rats in two studies (CAS 67762-53-2) resulted in no mortality and some clinical signs including hunched position, chromodacryorrhoea, piloerection, staining around nose and wet fur when tested with highest testable concentration (5.10 and 5.5 mg/mL respectively).

Acute dermal toxicity studies conducted with Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid (CAS 71010-76-9) showed no treatment related effects at the limit dose of the current valid guideline. Therefore, the dermal LD50 is considered to be greater than 2000 mg/kg bw.

Thus, the available data indicate a very low level of acute toxicity for the target and source substances and thus no hazard for acute oral, inhalative and dermal toxicity was identified.


Justification for selection of acute toxicity – oral 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 selection of acute toxicity – inhalation 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 selection of acute toxicity – dermal endpoint
Hazard assessment is conducted by means of read-across from structural analogue. The available study is 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 the information received for read-across from structurally similar substances, the available data on acute oral, inhalation and dermal toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.