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

Endpoint summary

Description of key information

Acute toxicity: oral

LD50 is greater than 2000 mg/kg body weight after single oral administration to Wistar rats.

Acute toxicity: dermal

The substance, CAS 68130-51-8; EC  268-594-6, is analogous to the substances to be read across to, in terms of basic form, and the degree of substitution of functional groups is not considered to effect the proposed read across for the endpoint of acute dermal toxicity. The substance is not considered to be acutely toxic via the dermal  route on the basis of read across.

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:

27 September 2017 to 12 October 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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

Specific details on test material used for the study:

No further details specified in the study report.

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.

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

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

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

 

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

K1

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Remarks:

1 substance available for read-across

Adequacy of study:

weight of evidence

Justification for type of information:

See the full attached justification in section 13 for details.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Hatcol 1570

Interpretation of results:

GHS criteria not met

Conclusions:

The substance, CAS 68130-51-8; EC 268-594-6, is analogous to the substances to be read across to, in terms of basic form, and the degree of substitution of functional groups is not considered to effect the proposed read across for the endpoint of acute dermal toxicity. The substance is not considered to be acutely toxic via the dermal route on the basis of read across.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 June 2010 To 08 July 2010

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000; including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Wistar strain, Crl:WI (Han)

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 11 weeks old)
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean.
- Housing: Individually housed in labeled Macrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material (Woody-Clean type 3/4, Tecnilab-BMI BV, Someren, The Netherlands) and paper as cage-enrichment (Enviro-dri, Tecnilab-BMI BV, Someren, The Netherlands).
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: The acclimatization period was at least 5 days before the start of treatment under laboratory conditions.
- Health inspection: A health inspection was performed prior to treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from any abnormality.

Results of analysis for diet (nutrients and contaminants), sawdust, paper and water were assessed and did not reveal any findings that were considered to have affected the study integrity. All certificates and results of analysis are retained in the NOTOX archives.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.9 – 21.5ºC
- Humidity (%): 41 - 78%
Temporary deviations from the maximum level of relative humidity occurred. Laboratory historical data do not indicate an effect of the deviations.
- Air changes (per hr): approximately 15 air changes per hour- Photoperiod (hrs dark / hrs light): 12 hours artificialfluorescent light and 12 hours darkness per day.

IN-LIFE DATES: From: 24 June 2010 To 08 July 2010

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.

The test substance was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D)*, successively covered with aluminum foil and Coban elastic bandage*. A piece of Micropore tape* was additionally used for fixation of the bandages in females only.
*. Manufacturers: Laboratoires Stella s.a., Liege, Belgium (surgical gauze) and 3M, St. Paul, Minnesota, U.S.A. (Coban & Micropore).

Frequency: Single dosage, on Day 1.

Washing: Following application, dressings were removed and the skin cleaned of residual test substance using tap water.

Duration of exposure:

24 hours.

Doses:

2000 mg/kg (2.105 mL/kg) body weight.
Dose volume calculated as dose level (g/kg) / specific gravity

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Dose level (volume): 2000 mg/kg (2.105 mL/kg) body weight.
Dose volume calculated as dose level (g/kg) / specific gravity.

DOSAGE PREPARATION: The test substance was dosed undiluted as delivered by the sponsor.

Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded.
- Necropsy of survivors performed: yes
- Other examinations performed: none.

Statistics:

None.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Chromodacryorrhoea (snout) was noted for two males and two females on Day 1. One of these females also showed lethargy and ptosis on Day 1. No further clinical signs were observed.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 value of Decanoic acid, mixed esters with heptanoic acid, octanoic acid and trimethylolpropane in Wistar rats was established to exceed 2000 mg/kg body weight.

Based on these results, Decanoic acid, mixed esters with heptanoic acid, octanoic acid and trimethylolpropane does not have to be classified and has no obligatory labeling requirement for acute dermal toxicity according to the:
- Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations (2007),
- Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

K1

Additional information

Acute toxicity: oral

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.

Acute toxicity: dermal.

The dermal LD50 value of Decanoic acid, mixed esters with heptanoic acid, octanoic acid and trimethylolpropane in Wistar rats was established to exceed 2000 mg/kg body weight.

Justification for classification or non-classification

Based on the above mentioned results, classification according to the CLP Regulation (EC)1272/2008 is not necessary.

A report justifying the read-across approach is included in IUCLID Chapter 13.