Hexanedioic acid, polymer with 2,2'-oxybis[ethanol]

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted according to OECD guideline 423 and GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Hexanedioic acid oligomeric reaction products with 2,2'-oxybis[ethanol]

EC Number:

618-460-1

Cas Number:

9010-89-3

Molecular formula:

(C6 H10 O4 . C4 H10 O3)x

IUPAC Name:

Hexanedioic acid oligomeric reaction products with 2,2'-oxybis[ethanol]

Constituent 2

Reference substance name:

Polyesterol 90212

IUPAC Name:

Polyesterol 90212

Test material form:

other: liquid

Details on test material:

Test substance:
colorless clear liquid

Homogeneity: The test item was homogeneous by visual inspection. Additionally homogeneity of the test item was ensured by shaking the test item container.

Storage stability: The stability of the test item under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility.

Storage conditions: Room temperature; avoid temperature < 0°C

Density: 1.072

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Test species/strain:
Wistar /Crl:WI(HAN) SPF

Supplier:
Charles River Wiga GmbH, Germany

Age on day 0:
young adult females (approx. 10 weeks)

Sex:
As suggested by the OECD guideline nulliparous and non-pregnant female animals were used for the test, because there is no indication that male animals are likely to be more sensitive to the acute effects of the test item.

Arrival in the testing facility:
Acclimatization period of at least 5 days before the beginning of the experimental phase; during the acclimatization period, the animals were accustomed to the environmental conditions of the study and to the diet.

Body weight on day 0: Animals of comparable weight (± 20% of the mean weight)

Room temperature/relative humidity:
22+/-3°C, 30-70%

Air changes per hour:
approx. 10

Day/night rhythm: 12/12 h (6 a.m. - 6 p.m./6 p.m.-6 a.m.)

Type of cage:
Makrolon, type II, single housing

Diet:
Feed: VRF1(P) (SDS Special Diets Services, 67122 Altrip, Germany), tap water ad libitum

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

ROUTE OF ADMINISTRATION:
Single oral administration by gavage

ADMINISTRATION VOLUME:
1.87 mg/kg bw

FASTING PERIOD:
Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.

TIME OF DAY OF ADMINISTRATION:
In the morning

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 in first step, another 3 in second step.

Control animals:

no

Details on study design:

SELECTION OF DOSES/CONCENTRATIONS:
By request of the sponsor a starting dose of 2000 mg/kg bw was chosen in the first step with 3 female animals. Because no mortality occurred, 2000 mg/kg bw were administered to another group of 3 female animals in the second step.

OBSERVATION PERIOD:
14 days

BODY WEIGHT DETERMINATION:
Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.

CLINICAL OBSERVATIONS:
Clinical signs for each animal were recorded several times on the day of administration and at least once during each workday thereafter.

MORTALITY:
A check for any dead or moribund animals was made at least once each workday; these records are archived by Bioassay.

PATHOLOGY:
Necropsy with gross-pathology examination was performed on the last day of the observation period after sacrifice by CO2-inhalation in a chamber with gradually increasing concentrations.

HISTOLOGY:
No histological examinations were performed.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality occurred.

Clinical signs:

other: Clinical signs in the first 2000 mg/kg test group revealed impaired general state and piloerection at hour 1 in one animal or from hour 1 until hour 2 in two animals after administration. No clinical signs were observed in the second 2000 mg/kg test group

Gross pathology:

There were no macroscopic pathological findings in the animals sacrificed at the end of the observation period (six females).

Any other information on results incl. tables

Table 1. Individual body weight changes.

Individual body weight changes
Dose (mg/kg bw):	2000					2000
Administration:	1					2
AnimalNo.:	R604	R605	R606	Mean weight	Standard deviation	R632	R633	R634	Mean weight	Standard deviation
Body weight at study day (g):
0	189	187	182	186.0	3.61	191	193	192	192.0	1.00
7	206	207	193	202.0	7.81	202	206	213	207.0	5.57
14	206	207	191	201.3	8.96	208	210	223	213.7	8.14

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study the median lethal dose of Polyesterol 90212 after oral administration was found to be greater than 2000 mg/kg bw in rats.

Executive summary:

In an acute oral toxicity study performed according to the Acute Toxic Class method, 2000 mg/kg of the undiluted test item Polyesterol 90212 were administered by gavage to two test groups of three fasted Wistar rats each (2000 mg/kg bw in 6 females).

The following test substance-related clinical observations were recorded, clinical signs occurred within the first 2 hours after administration:

2000 mg/kg (first test group):

• Impaired general state in all animals
• Piloerection in all animals
• No mortality occurred

2000 mg/kg (second test group):

• No clinical signs
• No mortality occurred

There were no macroscopic pathological findings in all surviving animals sacrificed at the end of the observation period. The mean body weight of two out of six animals increased within the normal range throughout the study period. In three females (two females of the first and one female of the second test group) body weights were within the normal range during the first week, but the animals revealed a stagnation of body weights during the second week. In one female of the first test group the body weight was within the normal range during the first week, but the animal revealed a marginal loss of body weight during the second week. This effect is observed at times in the rat strain used, because in the required age range the female animals have already reached the phase of slow growth. However, the known effect of slow growth cannot be attributed to the single animal, which showed marginal weight reduction, when compared to the weights of the other females. Nevertheless, the observed marginal weight reduction is considered to be unspecific, as the affected animal did not show any symptoms or change in behavior during the second week.

The acute oral LD50 was calculated to be > 2000 mg/kg bw.