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Description of key information

In an in vivo skin sensitization study conducted similar to OECD 429 with the target substance t-Butyl glycidyl ether in acetone/olive oil (4:1 v/v), four female CBA/Ca mice were tested using the method of the local lymph node assay by measuring the T:C ratio (which is equal to SI value). The T:C ratio of the test item was found to be 1.4, 2.2 and 5.6 for the concentration tested, respectively. Since the ratio was > 3 for one of the concentrations, t-Butyl glycidyl ether is considered to be a skin sensitizer. Griem et al., 2003 cited this study and based on the specific values further calculated the EC3 value with 31%. Based on this study, the target substance is considered to be a skin sensitizer and classification for Skin Sens 1B, H317 is warranted in accordance to CLP Regulation 1272/2008.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Principles of method if other than guideline:
- Principle of test: Measuring proliferation of lymphocytes in the lymph nodes draining the site of the test substance application
- Short description of test conditions: Groups of mice (n= 4) were treated by daily topical application for 3 consecutive days with 25 µL of one of three concentrations of the test chemical on the dorsum of each ear. Control mice were treated with vehicle alone in an identical manner. 5 days after the first topical application, all mice were injected i.v. with 250 µL phosphate buffered saline (PBS) containing 20 µCi of [3H]methyl thymidine (3HTdR). The mice were killed 5 hr later and the draining auricular lymph nodes excised and pooled for each experimental group. The proliferative response of the lymph node cells were measured by p-scintillation counting
- Parameters analysed / observed: T:C ratio (which is equal to SI value)
GLP compliance:
not specified
Type of study:
mouse local lymph node assay (LLNA)
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Aldrich Chemical Co., Gillingham, Dorset, UK
Species:
mouse
Strain:
CBA/Ca
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Females (if applicable) nulliparous and non-pregnant: Not specified
- Age at study initiation: 8 - 12 weeks
Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
10.0%, 25.0%, 50.0%
No. of animals per dose:
4 animals per goup. One animal per dose including a control animal.
Details on study design:
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Local lymph node assay
- Criteria used to consider a positive response: Chemical was regarded as a sensitizer in the LLNA if at least one concentration resulted in a T:C ratio (which is equal to SI value) of 3 or greater and the data were not incompatible with a biological dose response

TREATMENT PREPARATION AND ADMINISTRATION: Mice were treated by daily topical application for 3 consecutive days with 25 µL of one of three concentrations of the test chemical on the dorsum of each ear.
Positive control substance(s):
not specified
Positive control results:
Not specified
Parameter:
SI
Value:
1.4
Test group / Remarks:
Animal 1/ 10% concentration
Parameter:
SI
Value:
2.2
Test group / Remarks:
Animal 2/ 25.0% concentration
Parameter:
SI
Value:
5.6
Test group / Remarks:
Animal 3/ 50.0% concentration
Cellular proliferation data / Observations:
The T:C ratio (which is equal to SI value) of the test item as compared to the vehicle was found to be 1.4/2.2/5.6 for test concentrations of 10.0%, 25.0%,50.0% respectively, which is. Since the ratio was > 3 for one of the concentrations, the test item was considered to be a skin sensitizer.
Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
In this study, the test item is considered to be a skin sensitizer.
Executive summary:

In a an in vivo skin sensitization study conducted similar to OECD 429 with 1-tert-butoxy-2,3-epoxypropane in acetone/olive oil (4:1 v/v), four female CBA/Ca mice were tested using the method of the local lymph node assay by measuring the T:C ratio (which is equal to SI value). The T:C ratio of the test item was found to be 1.4, 2.2 and 5.6 for each concentration respectively. Since the ratio was > 3 for one of the concentrations, 1 -tert-butoxy-2,3-epoxypropane is considered to be a skin sensitizer.

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Qualifier:
no guideline followed
Principles of method if other than guideline:
The paper proposes a quantitative risk assessment methodology for skin sensitisation aiming at the derivation of safe exposure levels for sensitizing chemicals using EC3 values from the LLNA test in mice. For the test substance t-butylglycidyl ether (CAS 7665-72-7) the data presented in this review paper were first published by Basketter et al., 1994.
GLP compliance:
no
Type of study:
mouse local lymph node assay (LLNA)
Specific details on test material used for the study:
Not specified
Species:
mouse
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
n.a.
Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
n.a.
No. of animals per dose:
n.a.
Details on study design:
For details on study design please refer to Basketter et al., 1994 (see IUCLID section 7.4.1).
Positive control substance(s):
not specified
Statistics:
n.a.
Positive control results:
n.a.
Key result
Parameter:
EC3
Value:
31
Cellular proliferation data / Observations:
n.a.

The data presented in the review paper by Griem et al., 2003 is based on the LLNA data published by Basketter et al., 1994.

Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
In this review paper by Griem et al., 2003 the results from the LLNA published by Basketter et al., 1994 (see IUCLID section 7.4.1) were used to calculate the EC3 value. The EC3 value was calculated to be 31%. Thus, subcategorization as Skin Sens 1B, H317 is justified in accordance with CLP Regulation 1272/2008.
Executive summary:

In this review paper by Griem et al., 2003 the results from the LLNA published by Basketter et al., 1994 (see IUCLID section 7.4.1) were used to calculate the EC3 value. The EC3 value was calculated to be 31%. Thus, subcategorization as Skin Sens 1B, H317 is justified in accordance with CLP Regulation 1272/2008.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

In an in vivo skin sensitization study conducted similar to OECD 429 with the target substance t-Butyl glycidyl ether in acetone/olive oil (4:1 v/v), four female CBA/Ca mice were tested using the method of the local lymph node assay by measuring the T:C ratio (which is equal to SI value). The T:C ratio of the test item was found to be 1.4, 2.2 and 5.6 for the concentration tested, respectively. Since the ratio was > 3 for one of the concentrations, t-Butyl glycidyl ether is considered to be a skin sensitizer. Griem et al., 2003 cited this study and based on the specific values further calculated the EC3 value with 31%. Based on this study, the target substance is considered to be a skin sensitizer and classification for Skin Sens 1B, H317 is warranted in accordance to CLP Regulation 1272/2008.

Further data is available for the target substance.

In a repeated human insult patch test, 0.8% 1 -tert-butoxy-2,3 -epoxypropane in perchloroethylene was applied to the upper arms of 56 human panelists (males and females, 18 to over 60 years of age). The reactions were observed after a two-week incubation period. Two panelists exhibited positive reactions to 1-tert-butoxy-2,3-epoxypropane. One reaction was mild with redness and swelling confined to the test site. The other reaction was quite strong and spread beyond the test site. Based on these results, a skin sensitization potential of t-Butyl glycidyl ether might be possible.

There is one study from Rao, 1981 which indicated, that the target substance is a non-sensitizer. In a dermal sensitization study with 1-tert-butoxy-2,3-epoxy propane, 10 guinea pigs were tested using the method derived from the “split-adjuvant" technique, adopted from the Maguire method. After a preliminary test of applying the test substance as received, an aliquot of the substance was topically applied to the clipped and depilated backs of 10 guinea pigs four times in 10 days. At the time of the 3rd application, 0.2 mL of Freund's adjuvant was injected intradermally at one point adjacent to the insult site. After a 2-week rest period, the guinea pigs were challenged on the clipped flanks with the test material on one flank and a solvent (if used) on the other flank. The challenge site was evaluated for erythema and edema at 24 and 48 hours. The test substance 1 -tert-butoxy-2,3-epoxy propane did not produce a sensitization reaction in any of the 10 guinea pigs tested. Therefore, in this study, the test item is considered to be a non-sensitizer. Negative results were also reported in further in vivo skin sensitization test in guinea pigs.

In conclusion, based on the available data, the target substance is classified as Skin Sens 1B, H317.

Justification for classification or non-classification

Based on the available data, the target substance does warrant classification as Skin Sens 1B, H317 in accordance to CLP Regulation 1272/2008.