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Administrative data

Description of key information

- Skin irritation: not irritating (OECD TG 402)

- Eye irritation: severely irritating (irreversible effects on the eyes) (OECD TG 438)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin corrosion: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because an acute toxicity study by the dermal route does not indicate skin irritation up to the relevant limit dose level (2 000 mg/kg body weight)
Reason / purpose for cross-reference:
data waiving: supporting information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08-JUN-2017 to 20-JUL-2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 438 (Isolated Chicken Eye Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
chicken
Strain:
other: ROSS 308
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: TARAVIS KFT. 9600 Sárvár, Rábasömjéni út 129. Hungary
Heads were removed immediately after sedation of the chickens. The heads were transported to the lab at the earliest convenience for use approximately within 2 hours from collection. The ambient temperature was optimal (19.2ºC to 20.3ºC) during the transport.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent positive control
yes, concurrent negative control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 30 µL
Duration of treatment / exposure:
30, 75, 120, 180 and 240 minutes
Number of animals or in vitro replicates:
3 replicates
Details on study design:
SELECTION AND PREPARATION OF ISOLATED EYES
All eyes used in the assay were from the same groups of eyes collected on one specific day.
After collection, the heads were inspected for appropriate quality and wrapped with paper moistened with saline, then placed in a plastic box that can be closed (4 5 heads/box).
The eyelids were carefully cut away. The fluorescein-treated cornea was examined with hand-held slit lamp or slit lamp microscope, with the eye in the head, to ensure that the cornea was not damaged. If the cornea was in good condition, the eyeball was carefully removed from the orbit. The eyes were prepared and kept on the wet papers in a closed box so that the appropriate humidity was maintained.
The prepared eye was placed in a steel clamp and transferred to a chamber of the superfusion apparatus. The door of the chamber was closed except for manipulations and examinations, to maintain temperature and humidity.

EQUILIBRATION AND BASELINE RECORDINGS
If after examination the selected eyes were appropriate for the test, acclimatization started and was conducted for approximately 45 to 60 minutes. The temperature was verified to be in the range of 32 ± 1.5 °C in all chambers during the acclimatization and treatment periods.
At the end of the acclimatization period, a zero reference measurement was recorded for cornea thickness and opacity to serve as a baseline (t=0) for each individual eye. Following the equilibration period, the fluorescein retention was measured.

NUMBER OF REPLICATES : 3

NEGATIVE CONTROL USED : NaCl (9 g/L saline)

POSITIVE CONTROL USED : Acetic acid 10% (v/v) solution

APPLICATION DOSE AND EXPOSURE TIME : 30 µL for 30-240 minutes

OBSERVATION PERIOD : 240 minutes

REMOVAL OF TEST SUBSTANCE
- Volume and washing procedure after exposure period: after an exposure period of 10 seconds from the end of the application the cornea surface was rinsed thoroughly with 20 mL saline solution at ambient temperature

METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: score 0-4 in accordance with the guideline
- Damage to epithelium based on fluorescein retention: determined at baseline (t=0) and 30 minutes after the post-treatment rinse.
- Swelling: CS at time t = [ (CT at time t – CT at t=0) / CT at t=0 ] X 100
- Macroscopic morphological damage to the surface: yes
SCORING SYSTEM:
- Mean corneal swelling (%)
- Mean maximum opacity score
- Mean fluorescein retention score at 30 minutes post-treatment

DECISION CRITERIA: as indicated in the TG.
Irritation parameter:
percent corneal swelling
Remarks:
at up to 75 min
Value:
8
Negative controls validity:
valid
Positive controls validity:
valid
Irritation parameter:
percent corneal swelling
Remarks:
at up to 240 min
Value:
11
Negative controls validity:
valid
Positive controls validity:
valid
Irritation parameter:
cornea opacity score
Remarks:
mean maximum value
Value:
4
Negative controls validity:
valid
Positive controls validity:
valid
Irritation parameter:
fluorescein retention score
Remarks:
mean
Value:
2.3
Negative controls validity:
valid
Positive controls validity:
valid
Other effects / acceptance of results:
OTHER EFFECTS:
In this ICET, 2,5-Dimethoxytetrahydrofuran caused ocular corrosion or severe irritation in the enucleated chicken eyes. The overall ICE class was 1xII, 1xIII, 1xIV. Furthermore, Corneal opacity score 4 was observed in three eyes at 180 minutes after the post-treatment rinse.

DEMONSTRATION OF TECHNICAL PROFICIENCY:

ACCEPTANCE OF RESULTS:
The positive control Acetic acid 10% (v/v) solution was classed as corrosive/severely irritating, UN GHS Classification: Category 1.
The negative control NaCl (9 g/L saline) had no significant effects on the chicken eye in this study.
Positive and negative control values were within the corresponding historical control data ranges.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
In this ICET, 2,5-Dimethoxytetrahydrofuran caused ocular corrosion or severe irritation in the enucleated chicken eyes.
Executive summary:

The purpose of this Isolated Chicken Eye Test (ICET) was to evaluate the potential ocular corrosivity and irritancy of the test item 2,5-Dimethoxytetrahydrofuran by its ability to induce toxicity in enucleated chicken eyes. The test compound was applied in a single dose (30 µL/eye) onto the cornea of isolated chicken eyes and evaluated pre-treatment and at approximately 30, 75, 120, 180, and 240 minutes after the post-treatment rinse. The endpoints evaluated were corneal opacity, swelling, fluorescein retention, and morphological effects.

In this ICET, 2,5-Dimethoxytetrahydrofuran caused ocular corrosion or severe irritation in the enucleated chicken eyes. The overall ICE class was 1xII, 1xIII, 1xIV. Furthermore, Corneal opacity score 4 was observed in three eyes at 180 minutes after the post-treatment rinse.

Positive and negative controls showed the expected results. The experiment was considered to be valid.

According to the guideline OECD 438, 2,5-Dimethoxytetrahydrofuran is categorized as “Category 1”.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

In an acute toxicity study by the dermal route performed according to OECD TG 402, no indication of skin irritation was observed up the the limit dose of 2000 mg/kg bw.

Eye irritation:

In an Isolated Chicken Eye Test (ICET) performed according to OECD TG 438, 2,5-Dimethoxytetrahydrofuran was applied in a single dose (30 µL/eye) onto the cornea of isolated chicken eyes and evaluated pre-treatment and at approximately 30, 75, 120, 180, and 240 minutes after the post-treatment rinse. The endpoints evaluated were corneal opacity, swelling, fluorescein retention, and morphological effects.

In this ICET, 2,5-Dimethoxytetrahydrofuran caused ocular corrosion or severe irritation in the enucleated chicken eyes. The overall ICE class was 1xII, 1xIII, 1xIV. Furthermore, Corneal opacity score 4 was observed in three eyes at 180 minutes after the post-treatment rinse.

Positive and negative controls showed the expected results. The experiment was considered to be valid.

According to the guideline OECD 438, 2,5-Dimethoxytetrahydrofuran is categorized as “Category 1”.

Justification for classification or non-classification

Based on the absence of skin irritation in the acute toxicity study by the dermal route in rats, 2,5-Dimethoxytetrahydrofuran is not classified for skin irritation/corrosion according to UN/EU GHS criteria.

For eye irritation, according to the guideline OECD 438, 2,5-Dimethoxytetrahydrofuran is categorized as Category 1 H318 "Irreversible effect to the eyes".

No data are available for respiratory irritation; therefore no conclusion can be made on the classification of this endpoint.