Decanoic acid, mixed esters with dipentaerythritol, octanoic acid and valeric acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

08 Feb 2021 to 02 Mar 2021

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Report date:

2021

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

OECD Guideline 423. Acute Oral Toxicity - Acute Toxic Class Method, December 2001.

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

EPA Health Effects Test Guideline OPPTS 870.1100. Acute Oral Toxicity in Rodents, December 2002.

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

EC No 440/2008 Part B. Acute Oral Toxicity, Acute Toxic Class Method, May 2008.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Decanoic acid, mixed esters with dipentaerythritol, octanoic acid and valeric acid

EC Number:

270-470-1

EC Name:

Decanoic acid, mixed esters with dipentaerythritol, octanoic acid and valeric acid

Cas Number:

68441-66-7

Molecular formula:

not available due to complexity of the substance

IUPAC Name:

Decanoic acid, mixed esters with dipentaerythritol, octanoic acid and valeric acid

Test material form:

liquid

Details on test material:

Identification: Decanoic acid, mixed esters with dipentaerythritol, octanoic acid and valeric acid
Batch (Lot) Number: 2019194336
Expiry date: 03 June 2022
Physical Description: Clear light yellow liquid
Purity/Composition: UVCB
Storage Conditions: At room temperature

Additional information
Test Facility test item number: 212207/A
Purity/Composition correction factor: No correction factor required
Test item handling: No specific handling conditions required

Information about the purity and composition of the test item is not available since the test item is an UVCB (Substance of Unknown or Variable composition, Complex Reaction Products or Biological Materials). Since a sample relevant for the purpose of this study was tested, it was concluded that the study integrity was not affected by the omission of this
information.

Specific details on test material used for the study:

No further details specified in the study report.

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Species: Rat
Strain: Crl: WI(Han)
Condition: Outbred, SPF-Quality
Source: Charles River Deutschland, Sulzfeld, Germany
Number of Animals: 6 Females (nulliparous and non-pregnant). Each dose group consisted of 3 animals.
Age at the Initiation of Dosing: Young adult animals (approximately 8-9 weeks old) were selected.
Weight at the Initiation of Dosing: 145 to 173 g.

Animal Identification
At study assignment, each animal was identified using a subcutaneously implanted electronic identification chip.

Environmental Acclimation
The animals were allowed to acclimate to the Test Facility toxicology accommodation for at least 5 days before the commencement of dosing.

Selection, Assignment, Replacement, and Disposition of Animals
Animals were assigned to the study at the discretion of the coordinating biotechnician, with all animals within ± 20% of the sex mean body weights. Animals in poor health or at extremes of body weight range were not assigned to the study.
Before the initiation of dosing, a health inspection was performed and any assigned animal considered unsuitable for use in the study were replaced by alternate animals obtained from the same shipment and maintained under the same environmental conditions.
The disposition of all animals was documented in the study records.

Husbandry
Housing
On arrival and following assignment to the study, animals were group housed (up to 3 animals of the same sex and same dosing group together) in polycarbonate cages (Makrolon MIV type; height 18 cm.) containing sterilized wooden fibers as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) equipped with water bottles. The rooms in which the animals were kept were documented in the study records.
Animals were separated during designated procedures/activities. Each cage was clearly labeled.

Environmental Conditions
Target temperatures of 18 to 24°C with a relative target humidity of 40 to 70% were maintained. The actual daily mean temperature during the study period was 19 to 21°C with an actual daily mean relative humidity of 39 to 59%. The value that was outside the targeted range occurred for one day and was without a noticeable effect on the clinical condition of the animals or on the outcome of the study. A 12 hour light/12 hour dark cycle was maintained. Ten or greater air changes per hour with 100% fresh air (no air recirculation) were maintained in the animal rooms.

Food
Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) was provided ad libitum throughout the study, except during designated procedures.
The feed was analyzed by the supplier for nutritional components and environmental contaminants. Results of the analysis were provided by the supplier and are on file at the Test Facility.
It is considered that there were no known contaminants in the feed that would interfere with the objectives of the study.

Water
Municipal tap-water was freely available to each animal via water bottles.
Periodic analysis of the water was performed, and results of these analyses are on file at the Test Facility.
It is considered that there were no known contaminants in the water that would interfere with the objectives of the study.

Animal Enrichment
For psychological/environmental enrichment, animals were provided with paper (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom), except when interrupted by study procedures/activities.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

A single dose of test item was administered to the appropriate animals by oral gavage on Day 1, using a syringe with a plastic gavage cannula attached.
The dose volume for each animal was based on the body weight measurement prior to dosing. Dose volume (mL/kg body weight) was calculated as follows: Dose level (g/kg) / spec.gravity or density (g/mL) * purity correction factor.
The dosing formulations were stirred continuously during dose administration.
Animals were deprived of food overnight (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of the test item. Water was available.

The dose levels were based on the OECD test guidelines and were selected from the series 5 (lowest dose level), 50, 300 and 2000 (highest dose level) mg/kg body weight. The starting dose level should be the one that is likely to produce mortality in at least some of the animals and was selected based on available toxicity data of the test item. Since read-across studies showed that the oral LD50 of this class of substances is greater than 2000 mg/kg, a limit dose of 2000 mg/kg was used.

Doses:

Single dose

No. of animals per sex per dose:

3 animals/group

Control animals:

no

Details on study design:

In - Life Procedures, Observations, and Measurements
Mortality/Moribundity Checks
Throughout the study, animals were observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day. Animals were not removed from cage during observation, unless necessary for identification or confirmation of possible findings.

Clinical Observations
Post - Dose Observations
Post-dose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter. The observation period was 14 days.
All the animals were examined for reaction to dosing. The onset, intensity and duration of these signs was recorded (if appropriate), particular attention being paid to the animals for the first hour after dosing.

Body Weights
Animals were weighed individually on Day 1 (pre-dose), 8 and 15. A fasted weight was recorded on the day of dosing.

Terminal Procedures
All animals were sacrificed by oxygen/carbon dioxide procedure at the end of the observation period. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities were recorded.

Statistics:

Not specified in the study report.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: other: Erected fur or hunched posture was observed in the animals on Day 1 only.

Gross pathology:

No abnormalities were found at macroscopic postmortem examination of the animals.

Other findings:

No further findings specified in the study report.

Any other information on results incl. tables

Individual Mortality

Sex: Female Day(s): - Relative to Start Date

2000 mg/kg Group 1
	Day of Death	Removal date	Path Removal Reason
1	15	23-Feb-2021	TERM
2	15	23-Feb-2021	TERM
3	15	23-Feb-2021	TERM

 

2000 mg/kg Group 2
	Day of Death	Removal date	Path Removal Reason
4	15	02-Mar-2021	TERM
5	15	02-Mar-2021	TERM
6	15	02-Mar-2021	TERM

TERM = Terminal Euthanasia

 

Individual Clinical Observations

Group 1 Sex: Female 2000 mg/kg
	Observation Type: All Types	Day(s) Relative to Start Date
		1 0h	1 2h	1 4h	2	3	4	5	6	7	8	9	10	11	12	13	14	15
1	Fur, Erected	-	X	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
2	Fur, Erected	-	X	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
3	Fur, Erected	-	X	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-

 

Group 2 Sex: Female 2000 mg/kg
	Observation Type: All Types	Day(s) Relative to Start Date
		1 0h	1 2h	1 4h	2	3	4	5	6	7	8	9	10	11	12	13	14	15
4	Hunched posture	X	X	X	-	-	-	-	-	-	-	-	-	-	-	-	-	-
5	Hunched posture	X	X	X	-	-	-	-	-	-	-	-	-	-	-	-	-	-
6	Hunched posture	X	X	X	-	-	-	-	-	-	-	-	-	-	-	-	-	-

X = Present

- = Not Present

 

Individual Body Weights

Sex: Female Bodyweight (g)

2000 mg/kg Group 1	Day(s) Relative to Start Date
	1	8	15
1	157	183	200
2	150	185	189
3	145	174	188
Mean	150.7	180.7	192.3
SD	6.0	5.9	6.7
N	3	3	3

 

2000 mg/kg Group 2	Day(s) Relative to Start Date
	1	8	15
4	173	209	218
5	156	181	185
6	151	181	189
Mean	160.0	190.3	197.3
SD	11.5	16.2	18.0
N	3	3	3

 

Individual Macroscopic Pathology

Animal: 1 Group: 1 Sex: Female Dose: 2000 mg/kg Removal Reason: Terminal Euthanasia Study Day (Week) of Death: 15 (3) Gross Status: Complete Gross Pathology Observations: No observations found

Animal: 2 Group: 1 Sex: Female Dose: 2000 mg/kg Removal Reason: Terminal Euthanasia Study Day (Week) of Death: 15 (3) Gross Status: Complete Gross Pathology Observations: No observations found

Animal: 3 Group: 1 Sex: Female Dose: 2000 mg/kg Removal Reason: Terminal Euthanasia Study Day (Week) of Death: 15 (3) Gross Status: Complete Gross Pathology Observations: No observations found

Animal: 4 Group: 2 Sex: Female Dose: 2000 mg/kg Removal Reason: Terminal Euthanasia Study Day (Week) of Death: 15 (3) Gross Status: Complete Gross Pathology Observations: No observations found

Animal: 5 Group: 2 Sex: Female Dose: 2000 mg/kg Removal Reason: Terminal Euthanasia Study Day (Week) of Death: 15 (3) Gross Status: Complete Gross Pathology Observations: No observations found

Animal: 6 Group: 2 Sex: Female Dose: 2000 mg/kg Removal Reason: Terminal Euthanasia Study Day (Week) of Death: 15 (3) Gross Status: Complete Gross Pathology Observations: No observations found

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 value of Decanoic acid, mixed esters with dipentaerythritol, octanoic acid and valeric acid in Wistar Han rats was established to exceed 2000 mg/kg body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.
Based on these results, Decanoic acid, mixed esters with dipentaerythritol, octanoic acid and valeric acid does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

Executive summary:

The objective of this study was to assess the toxicity of the test item when administered in a single dose to female rats at one or more defined dosages. Furthermore, the results of the study allowed the test item to be ranked according to most classification systems, currently in use. This study should provide a rational basis for risk assessment in man.

The study was carried out in compliance with the guidelines described in:

OECD No.423 (2001) "Acute Oral Toxicity, Acute Toxic Class Method".

EC No 440/2008, part B: "Acute Oral Toxicity, Acute Toxic Class Method".

EPA, OPPTS 870.1100 (2002), "Acute Oral Toxicity".

JMAFF Guidelines (2000), including the most recent revisions.

Decanoic acid, mixed esters with dipentaerythritol, octanoic acid and valeric acid was administered by oral gavage to two consecutive groups of three female Wistar Han rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

No mortality occurred.

Erected fur or hunched posture was observed in the animals on Day 1 only.

The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.

No abnormalities were found at macroscopic postmortem examination of the animals.

The oral median lethal dose (LD50) value of Decanoic acid, mixed esters with dipentaerythritol, octanoic acid and valeric acid in Wistar Han rats was established to exceed 2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Based on these results, Decanoic acid, mixed esters with dipentaerythritol, octanoic acid and valeric acid does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).