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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

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 402 and GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

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:

male/female

Details on test animals or test system and environmental conditions:

Test species/strain:
Wistar rats/Crl:WI(Han) SPF

Age on day 0:
young adult animals (males approx. 8-10 weeks, females approx. 12-14 weeks)

Female animals were nulliparous and non-pregnant.

Supplier:
Chalres River Wiga GmbH, Germany

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

Type of cage:
Makrolon cage, type III, single housing

Feeding:
VRF1(P) (SDS Special Diets Services, 67122 Altrip, Germany)

Drinking water:
Tap water ad libitum

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Fur was clipped about 24 hours before administration.

Application area:
About 40 cm² (corresponds to at least 10% of the body surface)

Route of application:
Single application to the clipped epidermis (dorsal and dorsolaterale parts of the trunk); covering of the application site with a semi- occlusive dressing (4 layers of absorbent gauze and stretch bandage) for 24 hours. Afterwards removal of the semi- occlusive dressing, rinsing of the application site with warm water.

Observation period:
14 days

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw (1.87 mL/kg bw)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration:
14 days

- Frequency of observations and weighing:
Individual body weights were determined shortly before test item administration, weekly thereafter and on the last day of observation. Clinical observations were recorded several times on the day of administration and at least once during each workday thereafter. Skin findings were scored individually 30-60 minutes after removal of the semi-occlusive dressing (day 1), several times and on the last day of observation. A check for any dead or moribund animals was made at least once each workday.

- 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.

- Assessment of skin reactions:
The evaluation of skin reactions was performed according to Draize, J. H. "Dermal toxicity." Appraisal of the safety of chemicals in foods, drugs and cosmetics (1959): 46-59. Appraisal of the safety of chemicals in foods, drugs and cosmetics. The association of food and drug officials of the United States Austin, Texas:
Erythema and eschar formation:
0 No erythema
1 Very slight erythema (barely perceptible)
2 Well- defined erythema
3 Moderate to severe erythema
4 Severe erythema (beet redness) to eschar formation preventing grading of erythema
Edema formation:
0 No edema
1 Very slight edema (barely perceptible)
2 Slight edema (edges of area well- defined by definite raising)
3 Moderate edema (raised approx. 1 mm)
4 Severe edema (raised more than 1 mm and extending beyond area of exposure)
Descriptions of any dermal findings not covered by this scale were recorded.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality occured.

Clinical signs:

other: No systemic clinical signs were observed during clinical examination. Two male animals revealed very slight erythema on day 1 or from day 1 until day 2, respectively.

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.

Any other information on results incl. tables

Table 1.: Body weights:

Individual body weight changes
Dose (mg/kg bw):	2000
Sex:	male
Administration:	1
Animal No.:	R	R	R	R	R	Mean weight	Standard deviation
	607	608	609	610	611
Body weight at study day (g):
0	241	244	244	234	224	237.4	8.53
7	273	272	290	264	254	270.6	13.26
14	300	305	331	295	277	301.6	19.54
Individual body weight changes
Dose (mg/kg bw):	2000
Sex:	female
Administration:	1
Animal No.:	R	R	R	R	R	Mean weight	Standard deviation
	612	613	614	615	616
Body weight at study day (g):
0	206	202	214	205	209	207.2	4.55
7	215	211	218	209	211	212.8	3.63
14	225	218	221	213	216	218.6	4.62

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 (LD50) of Polyesterol 90212 after dermal application was found to be greater than 2000 mg/kg bw in male and female rats.

Executive summary:

In an acute dermal toxicity study (Limit Test), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of Polyesterol 90212 (undiluted) to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days.

No signs of systemic toxicity or mortality were observed in the animals.

The following test item-related local effects were recorded during the course of the study, local effects occurred within the first two days after administration:

• Very slight erythema (grade 1) in two male animals
• No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study.

The mean body weight of the all animals increased within the normal range throughout the study period with three exceptions in the female group. Two females revealed a stagnation of body weight during the whole observation period. One female animal showed stagnation of body weight during the first week, but the body weight was within the normal range 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. Due to the fact that stagnation of body weight is commonly known for females dermally applied, this stagnation is considered to be unspecific.

No mortality occurred. Accordingly, the acute dermal median lethal dose (LD50) was determined to be LD50, dermal, rat > 2000 mg/kg bw