2-ethylhexanoic acid, monoester with propane-1,2-diol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

3 July to 25 July 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study carried out according to OECD Guideline 401 (1987); performed according to GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-hydroxypropyl 2-ethylhexanoate

EC Number:

261-499-0

EC Name:

2-hydroxypropyl 2-ethylhexanoate

Cas Number:

58921-10-1

Molecular formula:

C11H22O3

IUPAC Name:

2-hydroxypropyl 2-ethylhexanoate

Constituent 2

Reference substance name:

1-hydroxypropan-2-yl 2-ethylhexanoate

Molecular formula:

C11H22O3

IUPAC Name:

1-hydroxypropan-2-yl 2-ethylhexanoate

impurity 1

Reference substance name:

Monoesters of 2-ethylhexanoic acid and dipropyleneglycol

IUPAC Name:

Monoesters of 2-ethylhexanoic acid and dipropyleneglycol

impurity 2

Reference substance name:

1-methylethylene 2-ethylhexanoate

EC Number:

301-185-3

EC Name:

1-methylethylene 2-ethylhexanoate

Cas Number:

93981-97-6

Molecular formula:

C19H36O4

IUPAC Name:

propane-1,2-diyl bis(2-ethylhexanoate)

impurity 3

Reference substance name:

2-ethylhexanoic acid

EC Number:

205-743-6

EC Name:

2-ethylhexanoic acid

Cas Number:

149-57-5

Molecular formula:

C8H16O2

IUPAC Name:

2-ethylhexanoic acid

impurity 4

Reference substance name:

Propane-1,2-diol, propoxylated

EC Number:

500-039-8

EC Name:

Propane-1,2-diol, propoxylated

Cas Number:

25322-69-4

IUPAC Name:

Propane-1,2-diol, propoxylated

impurity 5

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

Water

Test material form:

liquid: viscous

Specific details on test material used for the study:

Name of test material (as cited in study report): SER-AD FX 511
- Physical state: liquid
- Analytical purity: no data; identity, purity and stability of the test material were the responsibility of the sponsor
- Storage condition of test material: room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Ltd., Margate, Kent, UK
- Age at study initiation: 5 -8 w
- Weight at study initiation: 145-155 g (males), 135-147 g (females)
- Fasting period before study: overnight before dosing
- Housing: groups of up to five animals of the same sex in solid-floor polypropylene cages furnished with woodflakes
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-24
- Humidity (%): 47-66
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE: no vehicle was used; dose volume applied: 2.15 ml/kg
- Rationale for the selection of the starting dose: a range-finding test was conducted initially so as to determine the appropriate dose for the main study. Two animals ( one male, one female) were treated orally by gavage with a dose of 2000 mg/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5/sex/dose group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the animals were observed for mortality and clinical signs of toxicity 0.5, 1, 2 and 4 h post-treatment, and once per day for the whole observation period. Body weights were recorded on day 0, 4, and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: gross pathological examination

Statistics:

Not used, not necessary for such a type of study.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Range-finding study: no death of animals occured. Hunched posture and lethargy were observed, which returned to normal 1 day post-treatment. Hence, the dose of 2000 mg/kg bw was chosen for the main study.
Main study: no animal died during after administration of the test substance

Clinical signs:

other: Hunched posture, lethargy and ataxia were observed post-treatment. The animals appeared normal 1 day after dosing. Decreased reaspiratory rate was recorded in one male 2-4 hours after administration of the test material, which was reversible and was not o

Gross pathology:

No treatment-related abnormalities were detected in any of the animals tested in the post-moterm examinations.

Other findings:

- Organ weights: not recorded
- Histopathology: not performed due to no detected abnormalities in the gross pathological examination

Any other information on results incl. tables

Table 1: Individual body weights and weekly body weigh changes in the main study

Dose level (mg/kg bw)	Animal No	Body weight (g) at day			Body weight gaing (g) during week
		0	7	14	1	2
2000	Males
	1	146	195	233	49	38
	2	145	196	244	51	48
	3	155	221	280	66	59
	4	155	216	270	61	54
	5	155	219	281	64	62
	Females
	1	135	175	206	40	31
	2	142	172	200	30	28
	3	145	181	209	36	28
	4	147	186	207	39	21
	5	141	174	198	33	24

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material is of a low order of toxicity following a single oral exposure of rats. The LD50 is >2000mg/kg bw.

Executive summary:

In an acute oral toxicity study, groups of overnight fasted, young adult Sprague-Dawley CD rats 5/sex/dose, were given a single oral dose (by gavage) of 2000 mg/kg bw SER-AD FX 511 (unchanged) and were observed for 14 days. The dose was decided based on a prior-range finding study. The test material was found to be of a low order of acute toxicity following exposure of rats. No mortality was observed. The LD50 for both male and female rats is higher than 2000 mg/kg bw. Clinical signs on the day of dosing included hunched posture, ataxia and lethargy. One animal showed decreased respiratory rate. All clinical symptomps disappeared on day 1 after treatement. All animals except had gained weight 7 and 14 days following dosing. The post-moterm examination revealed no signs of adverse effects. On the basis of this study, SER- AD FX 511 does not warrant classification as being harmful or toxic.