Hexanedioic acid, 2,2,4(or 2,4,4)-trimethyl-, dimethyl ester

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2004-06-05 - 2004-07-21

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: 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)

Version / remarks:

(adopted December 17; 2001)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(Dir. 96/54 EEC)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

EPA 712-C-02-189; December 2002

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1,6-dimethyl (2R)-2,4,4-trimethylhexanedioate; 1,6-dimethyl (2S)-2,4,4-trimethylhexanedioate; 1,6-dimethyl (4R)-2,2,4-trimethylhexanedioate; 1,6-dimethyl (4S)-2,2,4-trimethylhexanedioate

EC Number:

700-087-1

Cas Number:

201872-72-2

Molecular formula:

C11H20O4

IUPAC Name:

1,6-dimethyl (2R)-2,4,4-trimethylhexanedioate; 1,6-dimethyl (2S)-2,4,4-trimethylhexanedioate; 1,6-dimethyl (4R)-2,2,4-trimethylhexanedioate; 1,6-dimethyl (4S)-2,2,4-trimethylhexanedioate

Details on test material:

Test substance: 2,2,4-(2,4,4)-trimethylhexanedioic acid dimethyl ester of Degussa AG.
Batch No.: Campaign 5 of 25 May 2004.
Approximately 40 % 2,2,4-isomer and 60 % 2,4,4-isomer
Stability: stable
Storage: at room temperature
Colour: light yellowish, clear
Physical state at room temperature: liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Test Animals:
- Strain: HsdBrlHan : WIST (SPF)
- Source: Harlan-Winkelmann GmbH, D-33178 Borchen (Germany)
- Weight at study initiation: 3 females 153-164 g (step 1); 3 females  152-153 g (step 2)
- Controls: no

Animal Husbandry:
- the animals were barrier maintained in an air conditioned room (22 +/- 3 °C; 55 +/- 10% rel. humidity; photoperiod: 12h ligh / 12h dark; air change 10 x / hour)
- Feeding ad libitum, Altromin 1324 maintenance diet for rats and mice, totally-pathogen-free (TPF)
- Free access to tap water (drinking water, municipal residue control, microbiol. controlled periodically)
- animals were kept in Macrolon cages on Altromin saw fiber bedding
- Adequate acclimatisation period

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Cottonseed oil

Details on oral exposure:

The animals were clinically observed prior to the administration. Prior to administration of the test item animals were fasted by withholding food overnight. Following the period of fasting the animals were weighted and the test item was administered. Then the food was withheld for a further 3-4 hours.
The test item was administered in a single dose by gavage using an intubation cannula according to body weight at a volume of 10 mL/kg bw.

Doses:

Starting dose (step 1 and 2): 2000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

Clinical examination:
Animals were observed for 14 days after dosing and were weighed prior to the administration and once a week thereafter. A clinical examination was made several times on the day of dosing. Part of this were at least three observations within the first four hours post-dose. Animals were observed once a day thereafter. Observations included changes in the skin and fur, eyes and mucous membranes.
Further observations: respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern . Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma

Pathology:
At the end of the observation period the animals were euthanised by an overdosage of pentobarbital and were subject to gross necropsy. All gross pathological changes were recorded.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

The dosage of 2000 mg/kg bw caused no compound-related mortality in any animals of step1 and 2 within the 14 days post-dose period.

Clinical signs:

other: No clinical signs of toxicity were observed during the study

Gross pathology:

No findings

Other findings:

No other treatment related effects were observed within this study

Any other information on results incl. tables

Absolute Body Weights in g
Animal No. / Sex	Day 0	Day 7	Day 14
Step 1 (2000 mg/kg bw)
1 / female	164	190	210
2 / female	158	188	213
3 / female	153	178	205
Step 2 (2000 mg/kg bw)
1 / female	153	164	198
2 / female	152	159	194
3 / female	153	177	190

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: EU GHS (EC Regulation 1272/2008) and EC Directive 67/548/EEC

Conclusions:

No treatment related mortality or any other sublethal symptoms were observed within the 14 day post-dosing period at step 1 and 2. According to the acute toxic class method regime, no further testing was required. Under the conditions of this acute oral toxicity test the test item showed no acute oral toxic characteristics.

Executive summary:

The acute oral toxicity to rats was evaluated by acute toxic class method. The test item was administerd to six female rats in a single dose by gavage at a dose fo 2000 mg/kg body weight. The animals were observed for mortality and any sub-lethal effects for 14 days after dosing.

No treatment related mortality or any other sublethal symptoms were observed within the 14 day post-dosing period at step 1 and 2. According to the acute toxic class method regime, no further testing was required. Under the conditions of this acute oral toxicity test the test item showed no acute oral toxic characteristics.