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Diss Factsheets

Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Justification for type of information:
The basis for this read-across approach is that the target substance is expected to undergo transformation into terephthalic acid (202-830-0; 100-21-0) and ethane-1,2-diol (203-473-3; 107-21-1). The toxicity of the metabolites will accurately predict the toxicity of the bis(2-hydroxyethyl)terephthalate (BHET; 959-26-2; 213-497-6). Refer to the JUSTIFICATION FOR READ-ACROSS OF TOXICOLOGICAL INFORMATION in Section 13 of this dossier for further details.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
read-across: supporting information
Reason / purpose for cross-reference:
read-across source
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
A radiotracer study was conducted in rats to determine the rate of absorption, distribution and excretion of the test substance following dermal application.
GLP compliance:
no
Remarks:
pre-dates GLP
Type of study:
other: A radiotracer study was conducted in rats to determine the rate of absorption, distribution and excretion of the test substance following dermal application.
Justification for non-LLNA method:
Study conducted in 1975
Specific details on test material used for the study:
radiolabelled [14C]-terephthalic acid
Species:
other: rat
Strain:
other: Charles River
Sex:
male
Details on test animals and environmental conditions:
The animals were adult male Charles River rats weighing 200-225 g. Animals were housed in metabolism cages during the study, and allowed free access to food and water.
Details on study design:
labeled TA were prepared in 1% solutions of Triton-X-100.
The doses of TA were applied in 0.2 ml of vehicle to the unabraded, depilated backs of rats. The rats received the same dose on alternate days for 10 consecutive days (five doses).
After dosing, the treated area of the back was covered with a gauze patch.
Key result
Group:
test chemical
Remarks on result:
no indication of skin sensitisation
Group:
positive control
Remarks on result:
not determinable because of methodological limitations
Group:
negative control
Remarks on result:
not determinable because of methodological limitations

At the time of final patch removal, there was no evidence of skin irritation at the application site of animals treated with [14C]-TA.

Interpretation of results:
GHS criteria not met
Conclusions:
The OECD SIDS document references this study and reports that terephthalic acid is not sensitizing.
Reason / purpose for cross-reference:
read-across source
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
according to Magnusson and Kligman
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was conducted in 1996 when the GPMT was an international accepted and recommended method to assess skin sensitizing properties.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Housing: individually, in stainless-steel wire-mesh cages

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 2°C
- Humidity (%): 55 ± 5%
Route:
intradermal and epicutaneous
Vehicle:
olive oil
Concentration / amount:
0.2 % (w/w) and 100 %
Route:
epicutaneous, occlusive
Vehicle:
olive oil
Concentration / amount:
100 %
No. of animals per dose:
4
Details on study design:
This test was performed according to the method of Magnusson and Kligman. A total of 19 guinea pigs were used. For sensitization, the solution for injection was prepared by mixing equal volumes of Freund's complete adjuvant and distilled water using two 5-mL glass syringes and stainless-steel syringe connector. The experimental dentin primers were diluted with olive oil and acetone (7: 3 v/v). Based on the findings of one of our previous papers, the 2-HEMA (2-hydroxyethyl methacrylate), HD (1,6-hexanediol) and EG (ethylene glycol) solutions for this test were diluted with olive oil and acetone at concentrations of 0.2% by weight. In the first stage of induction, 50 µL of each experimental dentin primer solution was intradermally injected into the back skin near the neck. One week later, as the second stage of induction, a filter paper patch soaked in 0.2 mL (100%) of experimental dentin primer was placed onto the shaved back of the guinea pigs. Finally, the experimental dentin primers (100 µL and 100% each) were applied to the skin at two sites using an Eppendorf filter paper under a sealed dressing for induction for 24 hours.
Positive control substance(s):
yes
Remarks:
2-hydroxyethyl methacrylate
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Group:
positive control
Dose level:
0.2% by weight
No. with + reactions:
10
Total no. in group:
10
Reading:
1st reading
Group:
negative control
Remarks on result:
not measured/tested
Interpretation of results:
GHS criteria not met
Conclusions:
Ethane-1,2-diol (203-473-3; 107-21-1) is not a skin sensitizer

Data source

Materials and methods

Test material

Constituent 1
Chemical structure
Reference substance name:
Bis(hydroxyethyl) terephthalate
EC Number:
213-497-6
EC Name:
Bis(hydroxyethyl) terephthalate
Cas Number:
959-26-2
Molecular formula:
C12H14O6
IUPAC Name:
bis(hydroxyethyl) terephthalate
Test material form:
solid
Specific details on test material used for the study:
Bis(2-hydroxyethyl) terephthalate value is read-across from supporting terephthalic acid (202-830-0; 100-21-0) and ethane-1,2-diol (203-473-3; 107-21-1) data.

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
other: Not applicable - read-across
Group:
test chemical
Remarks on result:
no indication of skin sensitisation
Reading:
other: not applicable
Group:
negative control
Remarks on result:
not measured/tested
Reading:
other: not applicable
Group:
positive control
Remarks on result:
not measured/tested

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Testing for each source substance, terephthalic acid (202-830-0; 100-21-0) and ethane-1,2-diol (203-473-3; 107-21-1), reported no skin sensitisation; therefore, it was predicted that BHET will not be sensitising to the skin.
Executive summary:

The in vivo skin sensitisation of terephthalic acid was assessed in guinea pigs. Terephthalic acid was reported to be non-sensitising to guinea pigs. Following the guinea pig maximization test methodology of Magnusson and Kligman, ethylene glycol was assessed for its skin sensitisation potential. The study reported that none of the four animals tested had a skin sensitisation reaction. For a substance to produce skin sensitisation, skin penetration to some extent would occur which would expose the target substance to esterases which would metabolize the target substance into the two source substances. As in vivo testing for each source substance reported no skin sensitisation, it was predicted that BHET will not be sensitising to the skin.