Registration Dossier

Administrative data

Description of key information

Acute toxicity:
Oral (OECD 420), rat: LD50 > 2000 mg/kg bw
Inhalation (OECD 403), rat: LC50 > 2.916 mg/L air
Dermal (OECD 402), rat: LD50 > 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
01 Apr - 16 Apr 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP - Guideline study
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
GROUPE INTERMINISTERIEL DES PRODUITS CHIMIQUES
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
other: Sprague Dawley (SPF Caw)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elevage JANVIER Labs, Le Genest St Isle, France
- Age at study initiation: 8 weeks
- Weight at study initiation: 182 - 201 g
- Fasting period before study: animals were fasted 1 day prior to substance administration until 4 hrs after substance administration (diet only).
- Housing: 3 animals per cage in solid-bottomed clear polycarbonate cages with stainless steel mesh lids
- Diet: A04, SAFE, Augy, France
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12 / 12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.19 mL/kg bw

Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 (including 1 animal from the sighting study and 4 additional animals in the main study)
Control animals:
other: 4 animals received 10 mL distilled water/kg bw via gavage in an additional study performed from 07 Jan - 21 Jan 2014.
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed 0.5, 1, 3 and 4 h after substance administration and daily thereafter; individual body weights were determined on Day 0 (prior to substance administration), 2, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: systematic examinations to identify any behavioural or toxic effects, macroscopical examination of oesophagus, stomach, duodenum, jejunum, ileon, caecum, colon, rectum, spleen, liver, thymus, trachea, lungs, heart, kidneys, urinary bladder, ovaries, uterus, adrenals and pancreas
Preliminary study:
No mortality or clinical signs related to toxicity were observed in the female exposed in the sighting study. Therefore, 4 additional animals were exposed to the test substance in a second step.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study.
Clinical signs:
No clinical signs related to toxicity were observed during the study.
Body weight:
Body weight gain appeared normal until the end of the observation period.
Gross pathology:
No macroscopic changes were observed after treatment with the test substance.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, 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 the 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 VII, 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:
key study
Study period:
09 Jun-25 Jun 1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP-Guideline study, tested with the source substance Octanoic acid ester with 1,2-propanediol, mono- and di- (CAS No. 31565-12-5). According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Bor: WISW (SPF Cpb)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Weight at study initiation: 247 - 259 g (males) and 231 - 252 g (females)
- Housing: Animals were housed individually in Makrolon III cages.
- Diet: Ssniff R 10 (Alleindiät für Ratten, Ssniff, Spezialfutter GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
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
- % coverage: 10
- Type of wrap if used: The test material was held in contact with the skin with an acrylastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test material was removed with warm water.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.06 cm³/kg bw
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: Animals were observed 30 min, 1, 2, 3, 4, 5 and 6 h post application and subsequently once daily. Individual body weights were determined on the day of application (Day 0) and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
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:
48 h after application 2 male and 1 female animal showed scaling. Scales were not apparent at the 72 h observation time point.
Body weight:
Body weight gains were within the normal ranges in males and females during the whole study period.
Gross pathology:
Necropsy revealed no substance-related findings. One male animal showed a slight swelling of the spleen possibly due to the termination of the study.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
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 the 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 VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Additional information

Acute Toxicity

Oral Route

A GLP-guideline study according to the fixed dose procedure (OECD 420) was determined to evaluate the acute toxicity of Fatty acids, vegetable-oil, esters with dipropylene glycol (Richeux, 2014). 5 female Sprague Dawley rats were exposed to 2000 mg test substance/kg bw via gavage. Up to the end of the observation period, no mortality or clinical signs of toxicity were observed and body weight gain appeared normal. No macroscopic changes were observed after treatment with the test substance. Thus, a LD50 > 2000 mg/kg bw was derived for Fatty acids, vegetable-oil, esters with dipropylene glycol.

 

Inhalation

There are no data available on acute toxicity following inhalation of Fatty acids, vegetable-oil, esters with dipropylene glycol. In accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5 read-across from an appropriate substance is conducted to fulfill the standard information requirements set out in Regulation (EC) No 1907/2006, Annex VIII, 8.5.

According to 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) “to avoid the need to test every substance for every endpoint”.

 

Fatty acids, vegetable-oil, esters with dipropylene glycol is a UVCB substance comprised of diesters based on 1,2-dipropylene glycol bonded to octanoic and decanoic acid (C8 – C10). Based on structural similarities and common functional groups, read-across to Decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7) is justified. For further details on the read-across approach, please refer to the analogue justification in Section 13 of the technical dossier.

 

The acute inhalation toxicity of Decanoic acid, mixed diesters with octanoic acid and propylene glycol was evaluated in two studies similar to OECD guideline 403 in a limit test (Re, 1978 a,b). A group of 10 male Sprague-Dawley rats and a group of 10 male and female guinea pigs and 3 control animals, respectively, were exposed whole body to 200 ppm (equivalent to 2.916 mg/L air) for 6 h. The animals were observed for a period of 7 days following administration.

No mortality occurred and no clinical signs of toxicity were apparent during the study period in any animal. Necropsy revealed no substance-related findings in both studies.

Therefore, the LC50 for male rats and male and female guinea pigs was greater than 200 ppm (2.916 mg/L).

Dermal route

There are no data available on acute toxicity following the dermal route for Fatty acids, vegetable-oil, esters with dipropylene glycol. In accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5 read-across from an appropriate substance is conducted to fulfill the standard information requirements set out in Regulation (EC) No 1907/2006, Annex VIII, 8.5.

According to 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) “to avoid the need to test every substance for every endpoint”.

 

Fatty acids, vegetable-oil, esters with dipropylene glycol is a UVCB substance comprised of diesters based on 1,2-dipropylene glycol bonded to octanoic and decanoic acid (C8 – C10). Based on structural similarities and common functional groups, read-across to Octanoic acid ester with 1,2-propanediol, mono- and di-( CAS 31565-12-5) is justified. For further details on the read-across approach, please refer to the analogue justification in Section 13 of the technical dossier.

 

CAS 31565-12-5

The acute dermal toxicity of Octanoic acid ester with 1,2-propanediol, mono- and di- was evaluated in rats in accordance with OECD guideline 402 under GLP conditions (Mürmann, 1992).

Groups of 5 rats/sex were treated with the undiluted test substance at the limit dose of 2000 mg/kg bw under semiocclusive conditions for 24 h. The animals were observed for a period of 14 days following administration. During the study period, no mortality and no clinical signs of toxicity occurred in any animal. Furthermore, no effects on body weight were noted.

No substance-related findings during necropsy were observed in any animal. In 3 animals, scaling was observed after 48 h, being no longer apparent at the 72 h observation time point.

Based on the study results, the dermal LD50 is considered to be greater than 2000 mg/kg bw.

 

Conclusion for acute toxicity

In summary, the test substance Fatty acids, vegetable-oil, esters with dipropylene glycol was not toxic after oral exposure resulting in an oral LD50 value > 2000 mg/kg bw. Acute dermal toxicity data from the structural analogue substance Octanoic acid ester with 1,2-propanediol, mono- and di- showed no mortality at the limit dose of 2000 mg/kg bw. Furthermore, no hazard was identified after inhalation of Decanoic acid, mixed diesters with octanoic acid and propylene glycol leading to a LC50 > 2000 mg/kg bw.

Thus, the available data indicate a very low level of acute toxicity for the test and analogue substance and thus no hazard for acute oral, dermal and inhalation toxicity was identified.


Justification for selection of acute toxicity – oral endpoint
There is only one study available.

Justification for selection of acute toxicity – inhalation endpoint
No study was selected as hazard assessment is conducted by a weight-of-evidence approach based on data from structural analogue substances. The available studies are adequate and reliable. The read-across is based on identified similarities in structure and intrinsic properties between the 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 a structural analogue. The selected study is an adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

Justification for classification or non-classification

The available data on acute toxicity (oral, dermal and inhalation) of the test substance and the structural analogue substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 and Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.