Reaction product of n-nonanoic acid (C9), n-heptanoic acid (C7), n-pentanoic acid (C5), mixed tetraesters with pentaerythritol, and 3,5,5-trimethylhexanoic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 June 2003 to 10 July 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study performed in accordance with OECD, EU & US EPA test guidelines in compliance with GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

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:

yes

Test material

Test material information

Constituent 1

Reference substance name:

144971-11-9

Cas Number:

144971-11-9

IUPAC Name:

144971-11-9

Constituent 2

Reference substance name:

Hatcol 3331

IUPAC Name:

Hatcol 3331

Test material form:

other: Clear colourless liquid

Details on test material:

Identification: Hatcol 3331
CAS Number: 144911-11-9
Description: Clear colourless liquid
Batch: D21287
Purity: 97.3%
Test substance storage: At room temperature in the dark
Stability under storage conditions: Not indicated
Expiry date: 01 September 2003
Specific Gravity: 0.969-0.976

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

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 Animals. Each dose group consisted of 3 animals of one sex (females were nulliparous and non-pregnant).
Age and body weight: Young adult animals (approx. 8 weeks old) were selected. Bodyweight variation did not exceed +1- 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: 17.2-23.2°C), a relative humidity of 30-70% (actual range: 48 - 83%) and 12 hours artificial fluorescent light and 12 hours darkness per day. Cleaning procedures in the room might have caused the temporary fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity.
Accommodation: Group housing of 3 animals per sex per cage in labelled Macrolon cages (type IV; height 18 cm.) containing purified sawdust as bedding material (SAWI, Jelu Werk, Rosenberg, Germany).
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).
Water: Free access to tap-water.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The toxicity of the test substance was assessed by stepwise treatment of groups of 3 animals.
The first group was treated at a dose level of 2000 mg/kg body weight. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups.

Doses:

2000 mg/kg (2.062 ml/kg) body weight.
Dose volume calculated as dose level: specific gravity.

No. of animals per sex per dose:

3 males and 3 females all receiving 2000 mg/kg

Control animals:

no

Details on study design:

TREATMENT
A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health.
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 (2.062 ml/kg) body weight. Dose volume calculated as dose level: specific gravity.

OBSERVATIONS
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:
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:

No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortaliy occurred.

Clinical signs:

other: Hunched posiure and piloerection were observed among all females on day 1. Males were without clinical signs.

Gross pathology:

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

Other findings:

No further findings detailed in the study report.

Any other information on results incl. tables

TABLE 1: CLINICAL SIGNS

TEST DAY		1	1	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15
HOURS AFTER TREATMENT	MAX	0	2	4
	GRADE
FEMALES 2000 MG/KG
ANIMAL 1
POSTURE
Hunched posture	(1)	1	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-
SKIN/FUR/PLUMAGE
Piloerection	(1)	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
ANIMAL 2
POSTURE
Hunched posture	(1)	1	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-
SKIN/FUR/PLUMAGE
Piloerection	(1)	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
ANIMAL 3
POSTURE
Hunched posture	(1)	1	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-
SKIN/FUR/PLUMAGE
Piloerection	(1)	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
MALES 2000 MG/KG
ANIMAL 4
NO CLINICAL SIGNS NOTED		-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
ANIMAL 5
NO CLINICAL SIGNS NOTED		-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
ANIMAL 6
NO CLINICAL SIGNS NOTED		-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-

- = SIGN NOT OBSERVED; . = OBSERVATION NOT PERFORMED; + = ANIMAL DEAD

 

TABLE 2: BODYWEIGHTS (GRAM)

SEX/DOSE LEVEL	ANIMAL	DAY 1	DAY 8	DAY 15
FEMALES 2000 MG/KG
	1	167	215	232
	2	173	216	247
	3	171	217	237
	MEAN	170	216	239
	ST.DEV.	3	1	8
	N	3	3	3
MALES 2000 MG/KG
	4	254	321	346
	5	254	338	381
	6	263	340	375
	MEAN	257	333	367
	ST.DEV.	5	10	19
	N	3	3	3

 

TABLE 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
MALES 2000 MG/KG
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:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The oral LD50 value of HATCOL 3331 in Wistar rats was established to exceed 2000 mg/kg body weight.

Executive summary:

Assessment of acute oral toxicity with HATCOL 3331 in the rat (Acute Toxic Class Method).

The study was carried out based on the guidelines described in: Environmental Protection Agency (EPA): Health Effects Test Guidelines OPPTS 870.1100. "Acute Oral Toxicity"; EC Commission Directive 96/54/EC, Part B.1 tris "Acute Toxicity-Oral, Acute Toxic Class Method", OECD No.423, "Acute Oral Toxicity - Acute Toxic Class Method" and JMAFF Japanese test guidelines.

 

HATCOL 3331 was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kg bodyweight. Animals were subjected to daily observations and weekly determination of bodyweight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occurred.

Hunched posture and piloerection were observed among all females on day 1. Males were without clinical signs.

The body weight gain shown by the animals over 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 HA TCOL 3331 in Wistar rats was established to exceed 2000 mg/kg bodyweight.

Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), HATCOL 3331 does not have to be classified and has no obligatory labelling requirement for oral toxicity.