Decanoic acid, mixed esters with heptanoic acid, isovaleric acid, octanoic acid and pentaerythritol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27 September 2017 to 12 October 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Acute Oral Toxicity-Acute Toxic Class Method, OECD Guideline for Testing of Chemicals No
423, Adopted: 17th December 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Decanoic acid, mixed esters with heptanoic acid, isovaleric acid, octanoic acid and pentaerythritol

EC Number:

268-594-6

EC Name:

Decanoic acid, mixed esters with heptanoic acid, isovaleric acid, octanoic acid and pentaerythritol

Cas Number:

68130-51-8

Molecular formula:

C25H44O8 to C45H84O8 (in CH2 unit increments)

IUPAC Name:

3-(heptanoyloxy)-2-[(octanoyloxy)methyl]-2-[(pentanoyloxy)methyl]propyl decanoate; 3-(heptanoyloxy)-2-{[(2-methylbutanoyl)oxy]methyl}-2-[(octanoyloxy)methyl]propyl decanoate

Test material form:

liquid

Details on test material:

Name Hatcol 1570
Batch no. B29855
Appearance slight yellow, clear liquid
CAS No. 68130-51-8
EINECS-No. 268-594-6
Molecular formula C10-H20-O2.C8-H16-O2.C7-H14-O2.C5-H12-O4.C5-H10-O2
Molecular weight not stated
Purity 99.7 %
Homogeneity homogeneous
Vapour pressure not stated
Stability H2O: not stated; EtOH: not stated; acetone: not stated; CH3CN: not stated; DMSO: not stated
Solubility H2O: not stated; EtOH: not stated; acetone: not stated; CH3CN: not stated; DMSO: not stated
Production date 14. Jun. 2017
Expiry date 14. Jun. 2019
Storage Room Temperature (20 ± 5°C)

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: Wistar rats
Source: Dobrá Voda, Slovak Republic
Number and Sex of Animals: 6 females
Age at First Dose: 8-12 weeks; female animals were non-pregnant and nulliparous
Animal Health: Health condition of animals was examined by a veterinarian before initiation of the study.
Acclimation: The animals were acclimated under the conditions identical to the conditions during the experiment 5 days prior to the start of treatment. The acclimation was according to the standard operation procedure.
Housing Condition: The animals were housed in plastic cages suspended on stainless steel racks, up to 3 animals per cage in a room equipped with central airconditioning. The average room temperature was maintained within the range of 23.4 ± 0.2° C, relative humidity within 54.4 ± 1.9 %. The light regimen was set to a 12-hour light /12-hour dark cycle. Sanitation was performed according to the standard operation procedures.
Diet: The laboratory food ssniff (Spezialdiäten GmbH, Germany) was offered at recommended doses each day approximately at the same time.
Water: The animals received tap water for human consumption. Drinking water was supplied ad libitum.
Bedding: Lignocel S3/4, Lufa - ITL GmbH, Germany
Animals Identification: The animals in the cage were marked by a line (I-III) on the tail with a waterproof marker. Each cage was marked with the study code, ID of animals and date of administration of the test item.
Justification for the Choice of Species: Normally females are used for testing OECD TG 423 because females are typically the more sensitive gender.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

The required amount of the test item (according to the body weight and dose) was mixed with vehicle (olive oil) shortly before administration.

Doses:

The starting dose could be selected from the fixed dose levels of 5, 50, 300, and 2000 mg/kg body weight. Available information indicated that the test item is likely to be non-toxic with regard to acute toxicity. A limit dose of 2000 mg/kg body weight was therefore used as a starting dose.

No. of animals per sex per dose:

One group of 3 females was dosed. Test item-related mortality was not observed during 24 hours and therefore in a second step another 3 females were treated at the same dose level.

Control animals:

no

Details on study design:

Dose Administration
The test item was administered in a single dose by gavage using a metal stomach tube. Animals were fasted prior to dosing (food but not water were withheld over-night). Following a period of fasting, animals were weighed and the test item administered. After test item administration, food was withheld for further 3-4 hours.

Clinical Observation
Animals were observed individually immediately after administration of the test item and 0.5, 1, 2, and 4 hours later. Each animal was inspected daily for the next 14 days.
Observations included: changes in skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity, and behavioural pattern. Particular attention was given to potential neurologic endpoints such as tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Body Weight
Individual weights of animals were measured immediately prior to test item administration and weekly thereafter. Weight differences after first and second weeks after administration were calculated and recorded.

Necropsy
All test animals were subjected to gross necropsy and the results were recorded for each animal.

Statistics:

Not specified

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All (6/6 females) animals survived the limit dose of 2000 mg/kg body weight.

Clinical signs:

other: During the follow up period, no animals displayed signs of intoxication, change of health, nor any other adverse reactions.

Gross pathology:

All animals were necropsied. During necropsy, no macroscopic findings were observed.

Other findings:

Not specified

Any other information on results incl. tables

Administration Results

Sex	Dose	ID	Results	Sex	Dose	ID	Results
Female	2000 mg/kg	1	Alive	Female	2000 mg/kg	4	Alive
		2	Alive			5	Alive
		3	Alive			6	Alive

 

Clinical Observation

Observation	Time After Administration
	Hour					Day
	Immediately	0.5	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
Skin and Hair	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Eyes	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Mucosa	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Respiratory System	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Respiratory System	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
CNS	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Somatomotoric Activity	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Tremor	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Spasms	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Salivation	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Diarrhoea	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Lethargy	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Sleep	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Coma	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Death	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-

- No observed signs

 

Body Weight

Sex	Dose	ID	Body Weight (g)			Body Weight Difference (g)
			Initial	Week 1	Week 2	Week 1 – Initial	Week 2 – Initial	Week 2 – Week 1
Female	2000 mg/kg	1	180	185	195	5	15	10
		2	180	180	185	0	5	5
		3	185	200	200	15	15	0
		4	180	180	190	0	10	10
		5	180	180	190	0	10	10
		6	180	190	200	10	20	10

 

Necropsy Results

Sex	Dose	ID	Results	Sex	Dose	ID	Results
Female	2000 mg/kg	1	No findings	Female	2000 mg/kg	4	No findings
		2	No findings			5	No findings
		3	No findings			6	No findings

 

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LD50 of the test item Hatcol 1570 is greater than 2000 mg/kg body weight after single oral administration to Wistar rats.

Based on Annex 2d Test Procedure with a Starting Dose of 2000 mg/kg body weight of OECD Guideline 423 it can be concluded that the test item Hatcol 1570 is classified in GHS Category 5/Unclassified with a LD50 cut off value equal to or greater than 5000 mg/kg body weight, after single oral administration to Wistar rats.

Executive summary:

The purpose of the study was to evaluate the potential toxic effect of the test item Hatcol 1570 when administered as a single oral dose to Wistar rats.

 

The procedure according to OECD Guideline 423 Acute Toxic Class (ATC) method was used.

 

Available information indicated that the test item is likely to be non-toxic; therefore, a limit dose of 2000 mg/kg body weight was used as a starting dose. One group of 3 females was dosed. Test item related mortality was not observed during 24 hours and therefore in a next step 3 females were treated with the same dose. All 6 females survived the limit dose. The limit dose of 2000 mg/kg body weight did not cause death or evident signs of toxicity. The body weights of 5 animals mildly increased during the study. Stagnation of body weight in one animal between the first and second week was observed. During necropsy, no macroscopic findings were observed.

 

The LD50 of the test item Hatcol 1570 is greater than 2000 mg/kg body weight after single oral administration to Wistar rats.

 

Based on Annex 2d Test Procedure with a Starting Dose of 2000 mg/kg body weight of OECD Guideline 423 it can be concluded that the test item Hatcol 1570 is classified in GHS Category 5/Unclassified with a LD50 cut off value equal to or greater than 5000 mg/kg body weight, after single oral administration to Wistar rats.