Registration Dossier

Acute oral LD50 ~ 3420 mg/kg bw

Acute inhalation 2h LC50 > 3.09 mg/L

Acute dermal LD50 > 3,061 mg/kg bw

Reference

Endpoint:

acute toxicity: 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

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 3 420 mg/kg bw

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 26.9 other: mmol/kg bw

Other findings:

The LD50 for terephthalic acid (202-830-0; 100-21-0) is reported as > 5000 mg/kg bw (> 30.1 mmol/kg bw)

The approximate lethal human dose for ethane-1,2-diol (203-473-3; 107-21-1) is reported as approximately 1670 mg/kg bw (~ 26.9 mmol/kg bw)

Based on a conservative prediction, the LD50 of BHET (959-26-2; 213-497-6) is predicted to be ~ 3420 mg/kg bw (~ 26.9 mmol/kg bw).

Interpretation of results:

GHS criteria not met

Conclusions:

Information on the source substances is considered to be directly applicable to an equivalent molar amount of the target substance; therefore, the LD50 of the target substance was predicted to be approximately 26.9 mmol/kg bw or approximately 3420 mg/kg bw.

Executive summary:

Information on the source substances is considered to be directly applicable to an equivalent molar amount of the target substance.

The acute oral toxicity of terephthalic acid was assessed in rats in a GLP-compliant acute oral toxicity study. Male and female Sprague-Dawley rats were exposure to a single dose of 5 000 mg/kg bw terephthalic acid and were observed for 14 days. No mortalities were reported, and no alterations were noted during gross necropsy. The acute oral LD₅₀ was reported as > 5 000 mg/kg bw or > 30.1 mmol/kg bw. Albion Wistar rats were used to assess the acute oral toxicity of ethylene glycol in a study that predates GLP. The acute oral LD₅₀ of ethylene glycol was reported as 8 450 mg/kg bw or 136.1 mmol/kg bw. However, clinical experience has identified ethylene glycol as more acutely toxic for humans than for laboratory animals following ingestion. The approximate lethal oral dose of 95% ethylene glycol is 1.5 ml/kg (1 670 mg/kg bw; 26.9 mmol/kg bw); therefore, the LD₅₀ of the target substance was predicted to be approximately 26.9 mmol/kg bw or approximately 3 420 mg/kg bw.

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

ca. 3 420 mg/kg bw

Reference

Endpoint:

acute toxicity: inhalation

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.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 3.09 mg/L air

Exp. duration:

2 h

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 0.012 other: mmol/L

Exp. duration:

2 h

Other findings:

The 2h LC50 for terephthalic acid (202-830-0; 100-21-0) is reported as > 2.02 mg/L (> 0.012 mmol/L)

The 6h LC50 for ethane-1,2-diol (203-473-3; 107-21-1) is reported as > 2.5 mg/L (> 0.040 mmol/L)

Based on a conservative prediction, the 2h LC50 of BHET (959-26-2; 213-497-6) is predicted to be > 3.09 mg/L (> 0.012 mmol/L).

Interpretation of results:

GHS criteria not met

Conclusions:

Information on the source substances is considered to be directly applicable to an equivalent molar amount of the target substance; therefore, the 2h LC50 of the target substance was predicted to be greater than 0.012 mmol/L or greater than 3.09 mg/L.

Executive summary:

Information on the source substances is considered to be directly applicable to an equivalent molar amount of the target substance.

The acute inhalation toxicity of terephthalic acid was assessed in rats in a GLP-compliant acute inhalation toxicity study. Male and female Sprague-Dawley rats were exposure for 2 hours to a single dose of 2.02 mg/L terephthalic acid and were observed for 14 days. No mortalities were reported. The acute 2h LC₅₀ was reported as > 2.02 mg/L or > 0.012 mmol/L. CD-1 female mice were used to assess the reproductive effects of repeated exposure to ethylene glycol by inhalation. The 6h LC₅₀ of ethylene glycol was > 2.5 mg/L or 0.040 mmol/L. The conservative 2h LC₅₀ of BHET was predicted to be greater than 0.012 mmol/L or greater than 3.09 mg/L.

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

> 3.09 mg/L air

Physical form:

inhalation: aerosol

Reference

Endpoint:

acute toxicity: dermal

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:

data waiving: 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

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3 061 mg/kg bw

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 12 other: mmol/kg bw

Other findings:

The dermal LD50 for terephthalic acid (202-830-0; 100-21-0) is reported as > 2000 mg/kg bw (> 12.0 mmol/kg bw)

The dermal LD50 for ethane-1,2-diol (203-473-3; 107-21-1) is reported as > 3549 mg/kg bw (> 57.2 mmol/kg bw)

Based on a conservative prediction, the dermal LD50 of BHET (959-26-2; 213-497-6) is predicted to be > 3061 mg/kg bw (> 12.0 mmol/kg bw).

Interpretation of results:

GHS criteria not met

Conclusions:

Information on the source substances is considered to be directly applicable to an equivalent molar amount of the target substance; therefore, the acute dermal LD50 of the target substance was predicted to be greater than 12.0 mmol/kg bw or greater than 3061 mg/kg bw.

Executive summary:

Information on the source substances is considered to be directly applicable to an equivalent molar amount of the target substance.

The acute dermal toxicity of terephthalic acid was assessed in New Zealand White rabbits in a GLP-compliant acute dermal toxicity study. Male and female rabbits were exposure 2 000 mg/kg bw terephthalic acid under occlusive conditions. The animals were observed for a total of 14 days. No mortality was reported and there were no alterations noted during gross necropsy. The dermal LD₅₀ was reported as > 2 000 mg/kg bw or greater than 12.0 mmol/kg bw. CD-1 female mice were used to assess the reproductive effects following repeated exposure to ethylene glycol by dermal exposure. The mice were repeatedly dermally exposed to various concentrations of ethylene glycol. The ethylene glycol was washed off after 6 hours of exposure. No deaths were reported during this repeated-dose study. Based on the highest concentration tested, the acute dermal LD₅₀ was greater than 3 549 mg/kg bw or greater than 57.2 mmol/kg bw. The conservative acute dermal LD₅₀ of BHET was predicted to be greater than 12.0 mmol/kg bw or greater than 3 061 mg/kg bw.

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 3 061 mg/kg bw

Information on the source substances is considered to be directly applicable to an equivalent molar amount of the target substance.

Acute toxicity: oral (REACH Annex VII 8.5.1)

The acute oral toxicity of terephthalic acid was assessed in rats in a GLP-compliant acute oral toxicity study. Male and female Sprague-Dawley rats were exposure to a single dose of 5 000 mg/kg bw terephthalic acid and were observed for 14 days. No mortalities were reported, and no alterations were noted during gross necropsy. The acute oral LD₅₀ was reported as > 5 000 mg/kg bw or > 30.1 mmol/kg bw. Albion Wistar rats were used to assess the acute oral toxicity of ethylene glycol in a study that predates GLP. The acute oral LD₅₀ of ethylene glycol was reported as 8 450 mg/kg bw or 136.1 mmol/kg bw. However, clinical experience has identified ethylene glycol as more acutely toxic for humans than for laboratory animals following ingestion. The approximate lethal oral dose of 95% ethylene glycol is 1.5 ml/kg (1 670 mg/kg bw; 26.9 mmol/kg bw); therefore, the LD₅₀ of the target substance was predicted to be approximately 26.9 mmol/kg bw or approximately 3 420 mg/kg bw.

Acute toxicity: by inhalation (REACH Annex VIII 8.5.2)

The acute inhalation toxicity of terephthalic acid was assessed in rats in a GLP-compliant acute inhalation toxicity study. Male and female Sprague-Dawley rats were exposure for 2 hours to a single dose of 2.02 mg/L terephthalic acid and were observed for 14 days. No mortalities were reported. The acute 2h LC₅₀ was reported as > 2.02 mg/L or > 0.012 mmol/L. CD-1 female mice were used to assess the reproductive effects of repeated exposure to ethylene glycol by inhalation. The 6h LC₅₀ of ethylene glycol was > 2.5 mg/L or 0.040 mmol/L. The conservative 2h LC₅₀ of BHET was predicted to be greater than 0.012 mmol/L or greater than 3.09 mg/L.

Acute toxicity: dermal (REACH Annex VIII 8.5.3)

The acute dermal toxicity of terephthalic acid was assessed in New Zealand White rabbits in a GLP-compliant acute dermal toxicity study. Male and female rabbits were exposure 2 000 mg/kg bw terephthalic acid under occlusive conditions. The animals were observed for a total of 14 days. No mortality was reported and there were no alterations noted during gross necropsy. The dermal LD₅₀ was reported as > 2 000 mg/kg bw or greater than 12.0 mmol/kg bw. CD-1 female mice were used to assess the reproductive effects following repeated exposure to ethylene glycol by dermal exposure. The mice were repeatedly dermally exposed to various concentrations of ethylene glycol. The ethylene glycol was washed off after 6 hours of exposure. No deaths were reported during this repeated-dose study. Based on the highest concentration tested, the acute dermal LD₅₀ was greater than 3 549 mg/kg bw or greater than 57.2 mmol/kg bw. The conservative acute dermal LD₅₀ of BHET was predicted to be greater than 12.0 mmol/kg bw or greater than 3 061 mg/kg bw.

Acute oral LD50 ~ 3420 mg/kg bw

Acute inhalation 2h LC50 > 3.09 mg/L

Acute dermal LD50 > 3061 mg/kg bw

Based on the Europe CLP (EC 1272/2008 as amended) criteria, the test item does not meet the criteria for classification as acutely toxic.