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Administrative data

Description of key information

In a primary in vivo skin irritation study New Zealand White rabbits were exposed to 0.5 mL with the source substance n-butyl glycidyl ether for 24 h and irritation scores were recorded at 24 h and 72 h. The average skin irritation score was found to be 2.8. N-butyl glycidyl ether is used as a read-across partner to the target substance t-Butyl glycidyl ether.

This result is supported by data from an in vivo skin irritation study in rabbit with the target substance (Norris, 1971). In this study, one female rabbit was dermally exposed to the target substance t-Butyl glycidyl ether ten times within eleven days. All skin irritating symptoms were fully reversible 10 days after the last application and within 21 days after the start of the application. Based on an evaluation of the available in a weight-of evidence approach, classification as Skin Irrit. 2, H315 is justified in accordance to CLP Regulation 1272/2008.

The eye irritancy potential of the target substance was investigated in the bovine corneal opacity and permeability assay (OECD 437). All three corneas treated with the target substance showed strong opacity of the tissue. The mean in vitro irritation score in the first and second experiment were 56.3 and 59 respectively. Thus, classification as Eye Dam. 1, H318 is warranted.

The result of the BCOP assay is supported by an in vivo eye irritation study by Rampy (1972). In this study, 2 drops of the target substance were applied to the right eye ball of one male rabbit after staining with fluorescein. Immediate response (pain), conjunctival response, corneal response (before and after staining), internal effects were examined using a scoring system. Severe pain, slight conjunctival inflammation, slight iritis very slight to slight corneal injury, which were not fully reversible within 6 days.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1971-04-19 to 1971-08-02
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: Evaluation of skin irritation properties
- Short description of test conditions: The test item will be applied under a 1 inch by 1 inch cotton pad and held in place by a cloth bandage taped to the hair. Ten applications are made over a period of 11 days. Further, the test material will applied to the ear. Ten applications are made over a period of 11 days. Reactions and observations are recorded daily during the application period and at varous intervals thereafter. Applications are usually discontinued upon production of a substantial skin burn.
- Parameters analysed / observed: Hyperemia, edema, necrosis, exfoliation, hair loss, scab, scar
GLP compliance:
not specified
Specific details on test material used for the study:
- Name: 1-tert-Butoxy-2,3-epoxypropane
- Appearance: colourless liquid
- Boiling point: 152 °C at 760 mmHg
- Solubility: Acetone, Benzene (> 25%)

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 01146-170-026, Source: A. Sexton
- Purity: > 99%
Species:
rabbit
Strain:
not specified
Remarks:
White laboratory rabbits
Details on test animals and environmental conditions:
female rabbit, body weight: 2.5 kg at the beginning of the study
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): no data
- Concentration (if solution): 100% (unchanged)

Duration of treatment / exposure:
On intact abdomen: 11 days (10 applications)
Observation period:
21 days (including 11 days application)
Number of animals:
one female
Details on study design:
White laboratory rabbits are prepared by shaving the hair from the entire abdomen with a straight razor and barber soap. The animal then rested for several days to allow any abrasions to heal completely and to be sure skin is suitable for use. The test item will be applied und er a 1 inch by 1 inch cotton pad and held in place by a cloth bandage taped to the hair. Ten applications are made over a period of 11 days. Further, the test material will applied to the ear. Ten applications are made over a period of 11 days. Reactions and observations are recorded daily during the application period and at varous intervals thereafter. Applications are usually discontinued upon production of a substantial skin burn.

SCORING SYSTEM:
- Method of calculation: Scoring system are provided in Table 1 in box "Any other information on materials and methods incl. tables".
Remarks on result:
not determinable because of methodological limitations
Irritant / corrosive response data:
Exposure to the test item material lead to redness, moderate swelling and a slight chemical burn as well as exfoliation. All symptoms were fully reversible max.10 days after the last application.
For individual results see table 2 and 3 in box "Any other information on results incl. tables"

Table 2: Irritation score on ear

Days on exposure 0 1 2 3 4 7 8 9 10 11 14 21
Application no. 1 2 3 4 5 6 7 8 9 10
Hyperemia 1 2 2 2 1 2 3 2+ 2 1 1
Edema 1 2 2 2 1 1 1 1 1 1 1
Necrosis 1 1 1 1 1 1 1 1 1 1 1
Exfoliation

1

1

1

3

2

1

2

2

3

1

1

Hair loss

1

1

1

1

1

1

1

1

1

1

1

Scab

1

1

1

1

1

1

1

1

1

1

1

Scar

1

1

1

1

1

1

1

1

1

1

1

Table 3: Irritation score on intact abdomen

Days on exposure

0

1

2

3

4

7

8

9

10

11

14

21

Application no.

1

2

3

4

5

6

7 8 9 10
Hyperemia 3+ 3+ 3 3 2 3 3- 3- 2+ 1 1
Edema 4+ 4+ 4 3 2 3 2 2 2 1 1
Necrosis 3 3+ 3 3 2

1

1

1

1

1

1

Exfoliation

1

3

3+

3+

4

4

4

4

4

3 +

1

Scab

1

1

1

1

1

2

3

2

1

1

1

Scar

1

1

1

1

1

1

1

1

1

1

1

Interpretation of results:
study cannot be used for classification
Conclusions:
In this study, 1-tert-Butoxy-2-,3-expoxypropane caused irritation on rabbit skin, which was fully reversible within 21 days.
Executive summary:

In an in vivo skin irritation study, one female white laboratory rabbit was dermally exposed to 1-tert-Butoxy-2-,3-expoxypropane (100% solution). Ten applications were made on the ear and the shaved intact abdomen within the first11 days. The animal was observed for a total 21 days. Irritation was scored according to a defined method. The following parameters were assessed: hyperemia, edema, necrosis, exfoliation, hair loss, scab and scar. All symptoms were fully reversible within 21 days. Due to the methodological deficiencies (multiple application, only one animal tested), this study cannot be used for classification. But, this study showed, that the effects observed were reversible within 21 days.

Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
The source compound n-butyl glycidyl ether (EC 219-376-4, CAS 2426-08-6) is considered a suitable read across partner for the target substance tert-butyl glycidyl ether (EC 231-640-0, CAS 7665-72-7). This read-across is based on the hypothesis that source and target substances have similar toxicological properties because:
- structural similarity of the target and the source substances (the presence or absence of additional functional groups or substituents that could influence the behaviour of a chemical),
- similarity in physico-chemical profile of the source and target substances (water solubility, partitioning behaviour (log Kow value))
Both substances are structural isomers regarding the alkyl chain structure with identical molecular weight. Both ethers have similar physico-chemical properties. Both are highly water soluble (20 g/L vs 90 g/L), exhibit similar log Kow values (0.63 vs 0.97), have similar boiling points (169 °C vs 152 °C) and vapour pressure (3.5 hPA vs 6.26 hPa).
Reason / purpose:
read-across source
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24/72 h
Score:
2.8
Max. score:
4
Reversibility:
not specified
Remarks on result:
other:
Remarks:
Irritation scores were only recorded at 24 and 72 hours
Irritant / corrosive response data:
The maximum injury score for erythema (4) was obtained in some rabbits.
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
In this study, under the given conditions, the test item showed mild irritant effects.
Executive summary:

In a primary dermal irritation study, New Zealand White rabbits were exposed to 0.5 mL of undiluted n-butyl glycidyl ether (BGE) for 24 h under occlusive conditions.Scoring of skin irriation was done according to Draize at 24 hours and 72 hours after application of the test material. An average skin irritation score of 2.8 was identified in the publication by Hine et al., 1956.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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:
2017-11-30 to
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)
Version / remarks:
adopted October 2017
Deviations:
no
Qualifier:
according to
Guideline:
EU method B.47 (Bovine corneal opacity and permeability test method for identifying ocular corrosives and severe irritants)
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
- Name in the test report: tert-Butyl glycidyl ether
- Homogeneity: homogeneous
- Appearance: clear, colourless liquid

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Bactch no. ZMG-195668
- Expiration date of the lot/batch: 2019-09-28

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Fridge (2 - 8 °C), keep container tightly closed in a dry, cool and well-ventilated place, keep cool and protect from sunlight
Species:
cattle
Strain:
other: Bos primigenius Taurus
Details on test animals or tissues and environmental conditions:
SOURCE OF COLLECTED EYES
- Source: Müller Fleisch GmbH, Enzstr. 2-4, 75217 Birkenfeld, Germany
- Age: 12 - 60 months
- Transport conditions of ocular tissue (e.g. transport time, transport media and temperature, and other conditions): Transport media: The exes were transported in Hank's balanced salt solution with 1 % Penicillin-Streptomycin solution (Penicillin 100 U/mL, Streptomycin 100 µg/mL) in a suitable cooled container.
- Time interval prior to initiating testing: 1 h incubation at 32 + / - 1 °C
- indication of any existing defects or lesions in ocular tissue samples: No
- Indication of any antibiotics used: Not specified
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent positive control
other: negative control: Hank’s Balanced Salt Solution
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 750 µL
- Concentration (if solution): undiluted
Duration of treatment / exposure:
10 min
Duration of post- treatment incubation (in vitro):
2 h
Number of animals or in vitro replicates:
3 per test group. 3 test groups
Details on study design:
SELECTION AND PREPARATION OF CORNEAS : After having carefully cleaned and sterilised the cornea holders, corneas were kept in the incubation chamber at 32 + / - 1 °C. On the day of the assay, the MEM without phenol red was supplemented with sodium bicarbonate, L-glutamine and 1% fetal calf serum (= complete MEM) and stored in a water bath at 32 + / - 1 °C. The same was performed with the MEM with phenol red, but without addition of sodium bicarbonate. After the arrival of the corneas, they were examined and only corneas which were free from damages were used. The corneas were excised with a scalpel and cut from the globe with a 2-3 mm ring of sclera around the outside. Each cornea was transferred to a cornea holder in which pre-warmed cMEM (32 + / - 1 °C) without phenol red was filled. The holders were then incubated for 1 hour in the incubation chamber at 32 + / - 1 °C.

NUMBER OF REPLICATES : 3

NEGATIVE CONTROL USED : Hank’s Balanced Salt Solution (HBSS) 10-fold concentrated, diluted in de-min. water (1:10)

POSITIVE CONTROL USED : Dimethylformamide (DMF)

EXPOSURE TIME : 10 min

TREATMENT METHOD: [closed chamber / open chamber] : Closed chamber

POST-INCUBATION PERIOD: yes/no. : Yes, 2 h

REMOVAL OF TEST SUBSTANCE
- Number of washing steps after exposure period: 2
- POST-EXPOSURE INCUBATION: 2 h

METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: change of opacity value of each treated cornea was calculated
- Corneal permeability: measured as optical density of the liquid with a microtiter plate photometer at 492 nm.

SCORING SYSTEM: In Vitro Irritancy Score (IVIS)

DECISION CRITERIA:
- IVIS ≤ 3: UN GHS No Category
- IVIS > 3 to ≤ 55: No prediction can be made
- IVIS > 55: UN GHS Category 1
Irritation parameter:
in vitro irritation score
Run / experiment:
Mean of three replicates: First experiment
Value:
56.3
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: equivocal, because two of the three replicates gave discordant predictions from the mean value
Irritation parameter:
in vitro irritation score
Run / experiment:
Mean of three replicates: Second experiment
Value:
59
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
positive indication of irritation
Other effects / acceptance of results:
OTHER EFFECTS:
- Visible damage on test system: No

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: Yes
- Acceptance criteria met for positive control: Yes

For individual results see Tables 1 &2 in box 'Any other information on results incl. tables'.

Table 1: IVIS values of the first experiment

Test group

IVIS

Mean IVIS

Relative standard deviation IVIS

Negative control HBSS

0.09

0.71

132.40 %

1.80

0.25

Test item tert-Butyl glycidyl ether

51.80

56.30

11.78 %

53.18

63.92

Positive control DMF undiluted

92.64

90.87

12.14 %

100.91

79.06

Table 2: IVIS values of the second experiment

Test group

IVIS

Mean IVIS

Relative standard deviation IVIS

Negative control HBSS

1.79

1.83

29.79 %

2.40

1.31

Test item tert-Butyl glycidyl ether

56.73

59.00

7.14 %

63.86

56.41

Positive control DMF undiluted

106.74

84.85

22.43 %

75.55

72.26

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
In conclusion, based on the mean in vitro irritation score of 59 obtained in the bovine corneal opacity and permeability assay (BCOP, OECD 437), the test substance needs to be classified as Eye Dam. 1 (H318) in accordance with Regulation (EC) No 1272/2008 (CLP).
Executive summary:

The eye irritancy potential of the test item was investigated in the bovine corneal opacity and permeability assay (OECD 437). The test item was incubated on the cornea for 10 minutes at 32 + / - 1 °C. After removal of the test item and 2 hours post-incubation, opacity and permeability values were measured. All three corneas treated with the test item showed strong opacity of the tissue. The mean in vitro irritation score in the first and second experiment were 56.3 and 59 respectively. The in vitro irritation score obtained with the positive control fell within the two standard deviations of the current historical mean and therefore this assay is considered to be valid. The negative control responses should result in opacity and permeability values that are less than the established upper limits for background bovine corneas treated with the respective negative control. Based on the results obtained the test substance has to be classified as Eye Dam. 1 (H318) in accordance with Regulation (EC) No 1272/2008 (CLP).

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a primary in vivo skin irritation study New Zealand White rabbits were exposed to 0.5 mL with the source substance n-butyl glycidyl ether for 24 h and irritation scores were recorded at 24 h and 72 h. The average skin irritation score was found to be 2.8. N-butyl glycidyl ether is used as a read-across partner to the target substance t-Butyl glycidyl ether.

This result is supported by data from an in vivo skin irritation study in rabbit with the target substance (Norris, 1971). In this study, one female rabbit was dermally exposed to the target substance t-Butyl glycidyl ether ten times within eleven days. All skin irritating symptoms were fully reversible 10 days after the last application and within 21 days after the start of the application. Based on an evaluation of the available in a weight-of evidence approach, classification as Skin Irrit. 2, H315 is justified in accordance to CLP Regulation 1272/2008.

The eye irritancy potential of the target substance was investigated in the bovine corneal opacity and permeability assay (OECD 437). All three corneas treated with the target substance showed strong opacity of the tissue. The mean in vitro irritation score in the first and second experiment were 56.3 and 59 respectively. Thus, classification as Eye Dam. 1, H318 is warranted.

The result of the BCOP assay is supported by an in vivo eye irritation study by Rampy (1972). In this study, 2 drops of the target substance were applied to the right eye ball of one male rabbit after staining with fluorescein. Immediate response (pain), conjunctival response, corneal response (before and after staining), internal effects were examined using a scoring system. Severe pain, slight conjunctival inflammation, slight iritis very slight to slight corneal injury, which were not fully reversible within 6 days.

Justification for classification or non-classification

Based on the available data, the target substance t-Butyl glycidyl ether is considered to be irritating to the skin and corrosive to the eyes. Thus, in accordance with CLP regulation 1272/2008 classification as Skin Irrit. 2, H315 and Eye Dam. 1, H318 is warranted.