Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Additional information

Oral Toxicity

  

The acute toxicity of di (2-ethylhexyl) terephthalate is well understood. In an acute oral toxicity study conducted according to Good Laboratory Practices (GLPs) and US TSCA FHSA regulations, di (2-ethylhexyl) terephthalate had an acute oral LD50 value of > 5000 mg/kg bw in male and female rats. No mortality was observed in the study, clinical signs were minimal, all animals gained weight during the study, and no treatment-related changes were observed at gross necropsy. Other lesser studies in rats and mice support the acute oral LD50 value. In those studies no deaths, no adverse clinical signs, and no adverse effects on weight gain were observed in animals administered up to 3200 mg/kg bw of di (2-ethylhexyl) terephthalate by the oral route. Based on these data, di (2-ethylhexyl) terephthalate is demonstrated to be a low order of acute toxicity following ingestion.

  

Dermal Toxicity

  

The acute dermal toxicity of di (2-ethylhexyl) terephthalate is well understood. Although an acute dermal toxicity study conducted according to OECD Guideline 402 was not identified, a non-guideline study conducted by a credible testing laboratory according to acceptable scientific methods of the time was available for review. In this study, doses of 5, 10 or 20 mL/kg bw (equivalent to 4920, 9840 or 19,680 mg/kg bw) di (2-ethylhexyl) terephthalate were applied to the depilated abdomens of guinea pigs under occluded contact for 24 hours. There were no deaths observed in this study. No signs of test material absorption or systemic toxicity were noted during the study and all animals gained weight during the observation period. The dermal LD50 is considered to be > 20 mL/kg bw (19,680 mg/kg bw). Based on the results of this study, di (2-ethylhexyl) terephthalate is considered to present a low acute toxicity hazard for skin contact. Although signs of irritation at the application site were observed, these followed 24-hour occluded contact with large volumes of test material, conditions much more stringent than are used in current guideline irritation studies.

  

Inhalation Toxicity

  

The acute inhalation toxicity of di (2-ethylhexyl) terephthalate is well understood. Although a study conducted according to OECD Guideline 403 was not identified, a subacute non-guideline study conducted by a credible testing laboratory according to acceptable scientific methods of the time was available for review. In this study (provided in detail in the Repeat-Exposure section of this submission), a group of 5 male albino rats was exposed to 0 or 0.0718 mg/L of di (2-ethylhexyl) terephthalate by whole body inhalation 5 days/week, 6 hours/day for 10 days over a 14 day period. Three days after the last exposure, animals were sacrificed, a gross necropsy was performed, organs weighed, and microscopic analysis performed. No deaths, clinical signs, or adverse effects on body weight gains were observed. All hematology and clinical chemistry parameters in exposed animals were comparable to controls. There were no treatment-related gross or microscopic lesions. Based on a No-Observed-Effect-Level of 0.0718 mg/L following repeated 6-hr exposures to di (2-ethylhexy) terephthalate, the LC50(6-hr) is considered to be at least 0.0718 mg/L. This exposure level could only be generated by passing an airflow of 6.0 L/min through a gas washing bottle containing undiluted di (2-ethylhexyl) terephthalate that was heated on a water bath at 95°C. Di (2-ethylhexyl) terephthalate is a liquid at room temperature with a low volatility. Exposure to vapors is unlikely because the vapor pressure is estimated to be 2.85 E-5 hPa at 25°C. Based on the physical properties of di (2-ethylhexyl) terephthalate, the potential for significant inhalation exposure is limited. Based on data from repeated exposure studies, di (2-ethylhexyl) terephthalate is considered to present a low acute toxicity hazard by the inhalation route.

Justification for classification or non-classification

Di (2-ethylhexyl) terephthalate was not previously classified under Directive 67/548/EEC, i.e., Annex I of the Dangerous Substances Directive for acute toxicity. Based on a weight-of-the-evidence assessment, di (2-ethylhexyl) terephthalate would not be classified for lethality by the oral, dermal, or inhalation routes according to the UN Globally Harmonized System of Classification and Labeling (GHS) or the EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) no. 1272/2008. Based on a weight–of-the-evidence assessment, di (2-ethylhexyl) terephthalate is also not classified for “Specific Target Organ Effects – Single Exposure”. No significant clinical signs, body weight changes or gross or microscopic observations to indicate systemic toxicity were observed by any route of exposure.