Decanoic acid, mixed esters with dipentaerythritol, heptanoic acid and octanoic acid.

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

30 March 2004 to 15 April 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

not specified

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

not specified

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

453-480-2

EC Name:

-

Cas Number:

70851-04-6

Molecular formula:

Not available

IUPAC Name:

Decanoic acid, mixed esters with dipentaerythritol, heptanoic acid and octanoic acid.

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl:(WI) BR (outbred, SPF-Quality).

Sex:

female

Details on test animals or test system and environmental conditions:

Test species:
Species: Rat, Wistar strain Crl:(WI) BR (outbred, SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. OECD, EC).
Source: Charles River Deutschland, Sulzfeld, Germany.
Number of animals: 6 Females (nulliparous and non-pregnant). Each dose group consisted of 3 animals.
Age and body weight: Young adult animals (approx. 8 weeks old) were selected. Body weight variation did not exceed +/- 20% of the sex mean.
Identification: Earmark.

Animal husbandry:
Conditions
Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 +/- 3.0°C (actual range: 17.5 -24.2°C), a relative humidity of 30-70% (actual range: 29 - 67%) and 12 hours artificial fluorescent light and 12 hours darkness per day.

Accommodation
Group housing of 3 animals per sex per cage in labelled Macroton cages (type IV; height 18 cm.) containing purified sawdust as bedding material {Woody Clean bedding (Woody-Clean type 3/4; Tecnilab-BMI BV, Someren, The Netherlands).
Certificates of analysis were examined and then retained in the NOTOX archives. Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.

Diet
Free access to standard pelleted laboratory animal diet (from Altromin (code VRF 1), Lage, Germany). Certificates of analysis were examined and then retained in the NOTOX archives.

Water
Free access to tap-water. Certificates of quarterly ana1ysis were examined and then retained in the NOTOX archives.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Method
Oral gavage, using a stainless steel stomach tube.

Fasting
Food was withheld overnight (for a maximum of 20 hours) prior to dosing until 3-4 hours after administration of the test substance.

Frequency
Single dosage, on day 1.

Dose level (volume)
2000 mg/kg (2.04 ml/kg) body weight.

Dose volume calculated as dose level: specific gravity.

Doses:

Single dose of 2000 mg/kg bw adminstered to animals on day 1

No. of animals per sex per dose:

3 animals per dose group (nulliparous and non-pregnant)

Control animals:

not specified

Details on study design:

Observations
Mortality/Viability: Twice daily.
Body weights: Day 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (day1) 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:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).

Necropsy: at the end of the observation period, all animals were sacrificed by asphyxiation using an oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.

Statistics:

Not applicable to this method.

Results and discussion

Preliminary study:

Not applicable

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:

Hunched posture was noted among the animals of the second group on day 1.

Body weight:

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

Gross pathology:

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

Any other information on results incl. tables

Clinical signs

Test day	Max grade	1	1	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15
Hours after treatment		0	2	4
Females 2000 mg/kg		-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Animal 1 No clinical signs noted		-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Animal 2 No clinical signs noted		-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Animal 3 No clinical signs noted		-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Females 2000 mg/kg
Animal 4 Hunched posture	(1)	1	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Animal 5 Hunched posture	(1)	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Animal 6 Hunched posture	(1)	1	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-

 

 

Body weights (gram)

Sex/Dose level	Animal	Day 1	Day 8	Day 15
Females 2000 mg/kg
	1	182	237	267
	2	164	212	238
	3	164	212	232
	Mean	170	220	246
	ST Dev.	10	14	19
	N	3	3	3
Females 2000 mg/kg
	4	180	217	229
	5	196	234	257
	6	183	215	234
	Mean	186	222	240
	ST Dev.	9	10	15
	N	3	3	3

                               

Macroscopic findings

Animal organ	Finding	Day of death
Females 2000 mg/kg
1	No findings noted	Scheduled necropsy Day 15 after treatment
2	No findings noted	Scheduled necropsy Day 15 after treatment
3	No findings noted	Scheduled necropsy Day 15 after treatment
4	No findings noted	Scheduled necropsy Day 15 after treatment
5	No findings noted	Scheduled necropsy Day 15 after treatment
6	No findings noted	Scheduled necropsy Day 15 after treatment

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 value of Hatcol 5127 in Wistar 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 om these results Hatcol 5127 does not have to be classified and has no obligatory requirement for oral toxicity according to the OECD Harmonized integrated Hazard Classification System for Human Health and Environmental Effects of Chemical Substances (OECD, 1998) and EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC).

Executive summary:

Assessment of acute oral toxicity with Hatcol 5127 in the rat (Acute Toxic Class Method).

The study was carried out based on the guidelines described in: "Acute Toxicity-Oral, Acute Toxic Class Method", OECD No.423 (2001); “Acute Oral Toxicity”; EC Commission Directive 96/54/EC, Part 8.1 tris (1996); Environmental Protection Agency (EPA): Health Effects Test Guidelines OPPTS 870.1100 (2002), "Acute Oral Toxicity- Acute Toxic Class Method" and JMAFF Japanese test guidelines (2000).

 

Hatcol 5127 was administered by oral gavage to two subsequent groups of three female rat Wistar 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.

 

Hunched pasture was noted among the animals of the second group on day 1.

 

The mean body weight gain shown by the animals aver the study period was considered to be normal.

 

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

 

The oral LD50 value of Hatcol 5127 in Wistar 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 Hatcol 5127 does not have to be classified and has no obligatory labelling requirement for oral toxicity according to the OECD Harmonized lntegrated Hazard Classification System for Human Health and Environmental Effects of Chemical Substances (OECD, 1998) and EC criteria for classification and labelling requirements for dangerous substances and preparations {Council Directive 67/54BIEEC).