Bis(hydroxyethyl) terephthalate

Carcinogenicity

Description of key information

As the effects noted for terephthalic acid (202-830-0; 100-21-0) are non-genotoxic and a threshold mode of action of limited relevance to the human risk assessment and ethane-1,2-diol (203-473-3; 107-21-1) is not oncogenic, BHET (959-26-2; 213-497-6) is predicted to be non-carcinogenic.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: oral

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.

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

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.

Species:

rat

Dose descriptor:

NOAEL

Effect level:

217 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: most conservative value

Dose descriptor:

NOAEL

Effect level:

0.8 other: mmol/kg bw/day

Based on:

test mat.

Sex:

female

Basis for effect level:

other: most conservative value

Conclusions:

As the effects noted for terephthalic acid (202-830-0; 100-21-0) are non-genotoxic and a threshold mode of action of limited relevance to the human risk assessment and ethane-1,2-diol (203-473-3; 107-21-1) is not oncogenic, BHET (959-26-2; 213-497-6) is predicted to be non-carcinogenic.

Executive summary:

Fischer-344 rats were exposed to 20, 142, or 1 000 mg/kg bw/day terephthalic acid in their diet for 24 months. This two-year feeding study showed increase incidence of calculi, bladder hyperplasia and tumors in rats. These effects were seen at doses of 2% and higher terephthalic acid in the diet. The induction of bladder tumors is believed to be a result of injury to the bladder epithelium from calculi formation. Transitional cell tumours were increased in high dose females and findings were associated with a chronic proliferative response to urolithiasis and therefore represent a non-genotoxic threshold mode of action of limited relevance to the human risk assessment. The oncogenicity of ethylene glycol was assessed in a study that pre-dates GLP by exposing Fischer-344 rats to 40, 200, or 1 000 mg/kg bw/day ethylene glycol in their diet for 24 months. In general, inclusion of ethylene glycol in the diet of Fischer-344 rats for 2 years resulted in a variety of marked toxic effects at the high dose level, the most pronounced of which was renal toxicity. Under the conditions of this study, ethylene glycol was reported as not oncogenic. Information on the source substances is considered to be directly applicable to an equivalent molar amount of the target substance; therefore, as neither source substance is concerned to be carcinogenic, BHET was predicted to be non-carcinogenic.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Justification for classification or non-classification

As the effects noted for terephthalic acid (202-830-0; 100-21-0) are non-genotoxic and a threshold mode of action of limited relevance to the human risk assessment and ethane-1,2-diol (203-473-3; 107-21-1) is not oncogenic, BHET (959-26-2; 213-497-6) is predicted to be non-carcinogenic.

Additional information

Fischer-344 rats were exposed to 20, 142, or 1 000 mg/kg bw/day terephthalic acid in their diet for 24 months. This two-year feeding study showed increase incidence of calculi, bladder hyperplasia and tumors in rats. These effects were seen at doses of 2% and higher terephthalic acid in the diet. The induction of bladder tumors is believed to be a result of injury to the bladder epithelium from calculi formation. Transitional cell tumours were increased in high dose females and findings were associated with a chronic proliferative response to urolithiasis and therefore represent a non-genotoxic threshold mode of action of limited relevance to the human risk assessment. The oncogenicity of ethylene glycol was assessed in a study that pre-dates GLP by exposing Fischer-344 rats to 40, 200, or 1 000 mg/kg bw/day ethylene glycol in their diet for 24 months. In general, inclusion of ethylene glycol in the diet of Fischer-344 rats for 2 years resulted in a variety of marked toxic effects at the high dose level, the most pronounced of which was renal toxicity. Under the conditions of this study, ethylene glycol was reported as not oncogenic. Information on the source substances is considered to be directly applicable to an equivalent molar amount of the target substance; therefore, as neither source substance is concerned to be carcinogenic, BHET was predicted to be non-carcinogenic.