Poly[oxy(methyl-1,2-ethanediyl)], α-hydro-ω-hydroxy-, ether with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol (3:1), 2-propenoate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation)

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From June 08, 2016 to June 23, 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Source: Velaz Prague, Czech Republic
Age at first dose: 8-12 weeks
Acclimation: 5 days prior to the start of treatment
Room temperature: 22 ± 2° C, relative humidity: 55 ± 10%
The light regimen was set to a 12-hour light /12-hour dark cycle
Diet: laboratory food Altromin (Altromin Spezialfutter GmbH, Germany), water: tap water

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

The required amount of the test substance (according to the body weight and dose) was mixed with vehicle (olive oil) shortly before administration. The test substance was administered in a single dose by gavage using a metal stomach tube. Animals were fasted prior to dosing (food but not water were withheld over-night). Following the period of fasting, the animals were weighted and the test substance administered. After the test substance had been administered, food was withheld for further 3-4 hours.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

no

Key result

Sex:

female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All 6/6 females survived the limit dose of 2000 mg/kg

Clinical signs:

other: Animals lived through observation period without signs of intoxication. Neither change of health nor negative reactions were registered

Gross pathology:

All animals were necropsied. During necropsy, no macroscopic changes were noticed

Interpretation of results:

GHS criteria not met

Conclusions:

Under the study conditions, the LD50 of the test substance was > 2000 mg/kg bw after single oral administration to rats.

Executive summary:

A study was conducted to determine the acute oral toxicity of the test substance according to OECD Guideline 423 (acute toxic class method), in compliance with GLP. The substance was administered by oral gavage to six female Wistar rats at 2000 mg/kg bw. Treated animals were observed for mortality, clinical signs and body weight changes for 14 d and were then subjected to gross pathological examination. No mortality was observed during the study. Animals lived through the observation period without signs of intoxication. Neither changes of health nor negative reactions were recorded. No body weight losses were observed in the first and second week after administration. In 2 animals, stagnation of body weight was observed. All animals were necropsied and no macroscopic changes in the organs were observed. Under the study conditions, the LD50 of the test substance was > 2000 mg/kg bw after single oral administration to rats (Hozova, 2016).

Cross-reference 2

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From June 27, 2016 to July 01, 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test system:

human skin model

Source species:

human

Cell type:

non-transformed keratinocytes

Details on animal used as source of test system:

Commercially available EpiDermTM-Kit (from MatTek In Vitro Life Science Laboratories, Bratislava). T he EpiDermTM tissue consists of human-derived epidermal keratinocytes which have been cultured to f orm a multi-layered, highly differentiated model of the human epidermis. It consists of organized basal, spinous and granular layers, and a multi-layered stratum corneum containing intercellular lamellar lipid layers arranged in patterns analogous to those found in vivo. The EpiDermTM tissues are cultured on specially prepared cell cultures inserts.

Vehicle:

unchanged (no vehicle)

Details on test system:

The test consists of a topical exposure of the neat test substance to a human reconstructed epidermis model followed by a cell viability test. Cell viability is measured by dehydrogenase conversion of MTT 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide, present in cell mitochondria, into a blue formazan salt that is quantitatively measured after extraction from tissues. The percentage reduction of cell viability in comparison of untreated negative controls is used to predict skin irritation potential.

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

30 μL of undissolved test substance

Duration of treatment / exposure:

60 min

Duration of post-treatment incubation (if applicable):

ca. 42 h 30 min. Following this post-incubation period, the MTT test was performed

Number of replicates:

3

Controls:

yes, concurrent no treatment

Irritation / corrosion parameter:

% tissue viability

Remarks:

% formazan production

Run / experiment:

MMT test (relative absorbance value)

Value:

96.5

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Other effects / acceptance of results:

After treatment with the negative control, the absorbance values were within the required acceptability criterion of 0.8 ≤ mean OD ≤ 2.8, OD was 1.9. The positive control showed clear irritating effects. Relative absorbance was reduced to 3.5 % (required: < 20%). Variation within the tissue replicates was acceptable (required: ≤ 18%).
After the treatment with the test substance, the relative absorbance values were reduced to 96.5 %. This value is above the threshold for skin irritation potential (50%). Therefore, the est substance was considered as non-irritant to skin in the Human Skin Model Test.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the study conditions, the test substance was considered not to be iirritating to skin in the Human Skin Model Test.

Executive summary:

A study was conducted to determine the in vitro skin irritation potential of the test substance according to OECD Guideline 439 and EU Method B.46 (Reconstructed Human Epidermis Test Method), in compliance with GLP. Three tissues were exposed for 60 min to 30 µL of undissolved test substance. After a post-incubation period of 42.5 h, the MTT test was performed. Cell viability was measured by dehydrogenase conversion of MTT, present in cell mitochondria, into a blue formazan salt that is quantitatively measured after extraction from tissues. The percentage reduction of cell viability in comparison of untreated negative controls was used to predict skin irritation potential. After treatment with the negative control (DPBS-buffer), the absorbance values were within the required acceptability criterion of 0.8 ≤ mean OD ≤ 2.8, OD was 1.9. The positive control (sodium dodecyl sulphate) showed clear irritating effects. Relative absorbance was reduced to 3.5% (requirement: ≤ 20%). After the treatment with the test substance, the relative absorbance values were reduced to 96.5%. This value is well above the threshold for irritation potential (50%). Based on the results obtained, the experiment was considered valid. Under the study conditions, the test substance was considered not to be irritating to skin (Andres, 2016).