Bis(hydroxyethyl) terephthalate

Skin irritation / corrosion

Administrative data

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 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-reference

Cross-reference 1

Reason / purpose for cross-reference:

read-across: supporting information

Cross-reference 2

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Guideline:

other: Not Reported

GLP compliance:

yes

Species:

rabbit

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable because of methodological limitations

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable because of methodological limitations

Irritation parameter:

overall irritation score

Remarks on result:

no indication of irritation

Interpretation of results:

GHS criteria not met

Conclusions:

Terephthalic acid is not irritating to skin.

Cross-reference 3

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1982

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

- Reliability scoring based on 2002 guideline.

Deviations:

yes

Remarks:

- Insufficient details on test substance and study design; no individual data.

GLP compliance:

no

Specific details on test material used for the study:

test concentration: 100%
Reported as: Ethylene glycol

Species:

rabbit

Strain:

not specified

Type of coverage:

occlusive

Preparation of test site:

not specified

Vehicle:

other: undiluted and diluted in water

Controls:

no

Duration of treatment / exposure:

Not reported.

Observation period:

Not reported.

Number of animals:

Not reported.

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable because of methodological limitations

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable because of methodological limitations

Irritation parameter:

other: Primary cutaneous irritation index

Basis:

mean

Remarks:

Undiluted test substance

Time point:

other: Not reported

Score:

0.08

Max. score:

2

Reversibility:

no data

Other effects:

Results for rabbits tested with 10% diluted in water not reported. No further details reported.

Interpretation of results:

other: unable to classify, documentation insufficient for assessment.

Conclusions:

Ethylene glycol is not irritating to skin.

Cross-reference 4

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1982

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Qualifier:

no guideline available

Principles of method if other than guideline:

6-week cumulative irritation test in rabbits.

GLP compliance:

no

Specific details on test material used for the study:

test concentration: 100%
Reported as: Ethylene glycol

Species:

rabbit

Strain:

not specified

Type of coverage:

not specified

Preparation of test site:

not specified

Vehicle:

water

Controls:

no

Duration of treatment / exposure:

6 weeks

Observation period:

Daily readings for 6 weeks of treatment. Study of recovery from cutaneous injuries by stopping application for 7 days and examining the skin after this rest.

Number of animals:

3 rabbits.

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable because of methodological limitations

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable because of methodological limitations

Irritation parameter:

other: MMII

Basis:

mean

Remarks:

-Undiluted test substance

Time point:

other: Addition of the erythema and oedema scores obtained each week (from five daily readings)

Score:

0.47

Reversibility:

no data

Remarks on result:

other: Well tolerated; Maximum score not reported

Irritation parameter:

other: MMII

Basis:

mean

Remarks:

-10% test substance

Time point:

other: Addition of the erythema and oedema scores obtained each week (from five daily readings)

Score:

0

Reversibility:

no data

Remarks on result:

other: Very well tolerated; Maximum score not reported

Other effects:

Cumulative cutaneous irritation index: Concerning the skin response to repeated exposure, the interpretation is more complex because for the series of products tested after several applications, erythema was noted lasting until the final test. This erythema, scarcely visible for the diluted materials, was more serious when the products were tested undiluted. It was also frequently observed that vesicles appeared for spasmodic or prolonged periods, as well as papules, maculae, or patches of erythema. However, if the presence of vesicles is an allergic reaction in the human, it would appear that this is not applicable to the rabbit because in this event 60 to 70% of cosmetics would appear to contain allergy-inducers. It appears that this is due to an occlusive film formed by the remaining material, in spite of all the precautions taken to remove the excess of test substance. The pores in the skin of a rabbit are more dilated than those of human skin and materials tend to accumulate in these cavities. Furthermore, these products, when applied under the same conditions to hairless or normal rats, rarely provoke the appearance of vesicles. 

Interpretation of results:

other: unable to classify, documentation insufficient for assessment.

Conclusions:

Ethylene glycol is not irritating to skin.

Materials and methods

Test material

Test material information

Constituent 1

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

Results

Results 1

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable

Results 2

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable

Results 3

Irritation parameter:

overall irritation score

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Neither the terephthalic acid (202-830-0; 100-21-0) nor ethane-1,2-diol (203-473-3; 107-21-1) metabolites are irritating to the skin. Therefore, it was predicted that bis(2-hydroxyethyl)terephthalate (BHET; 959-26-2; 213-497-6) will not be irritating to the skin.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Neither the terephthalic acid (202-830-0; 100-21-0) nor ethane-1,2-diol (203-473-3; 107-21-1) metabolites are irritating to the skin. Therefore, it was predicted that bis(2-hydroxyethyl)terephthalate (BHET; 959-26-2; 213-497-6) will not be irritating to the skin.

Executive summary:

The in vivo skin irritation of terephthalic acid was assessed in rabbits in a GLP-compliant abbreviated acute dermal irritancy/corrosivity study. No irritancy or corrosivity was observed. Guillot, et al. assessed the in vivo skin irritation of ethylene glycol in a non-GLP-complaint study following the procedure described in the Journal Officiel de la République Française. No irritancy was reported following either single contact or repeated application for 6 weeks. For a substance to produce skin irritation, 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 irritation, it was predicted that BHET will not be irritating to the skin.