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Description of key information

Studies indicate that isophthalic acid is of very low toxicity by the oral, inhalation and dermal routes.  Acute oral LD50 values of >5000, 10900 and 13000 mg/kg bw are reported.  An inhalation LC50 of greater than 11.37 mg/L is reported. A dermal LD50 of >2000 mg/kg bw is also reported.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
10 900 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50
Value:
11 370 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Acute oral toxicity

The acute oral toxicity of isophthalic acid has been investigated in three studies in the rat; the results of the studies are consistent in demonstrating very low toxicity. In a study conducted in 1990 (IIT, 1990), 10 Sprague Dawley rats (5/sex) were exposed to a 33% (w/v) aqueous suspension of isophthalic acid via oral gavage at a dosing volume of 15 mL/kg bw (equivalent to a dose of 5000 mg/kg bw). Based on the results of this study, the LD50 was estimated to be greater than 5 g/kg bw in male and female rats. In two studies by Harrison & Mastri (1975a,b), the LD50 for isophthalic acid was determined to be 13000 and 10900 mg/kg bw.

Acute inhalation toxicity

IPA study

The acute inhalation toxicity of isophthalic acid was investigated in 5 male and 5 female Sprague-Dawley rats (Kay, 1958). The rats were exposed to 11370 mg/m3 isophthalic acid dust (particle size 1 to 5 microns) for four hours. There were no mortalities and no signs of toxicity during the exposure period or the 14 day post-exposure observation period. The results of this study indicate that the LC50 is greater than 11370 mg/m3.

TPA studies

In a study investigating toxicity from pyrotechnic dissemination Thomson et al (1988), male F344 rats were exposed to pyrotechnically disseminated terephthalic acid in nose-only exposure chambers for 30 minutes. Nominal terephthalic acid concentrations were 100, 200 and 400 mg/m³. Two control groups were exposed to either air alone, or the fuse/fuel mix alone. Rats underwent pulmonary function tests and bronchoalveolar lavage immediately prior to sacrifice, at 24 hours or 14 days post exposure. There were no compound-related mortalities. There were no adverse changes in pulmonary function, lavage or histopathology. The only adverse reaction observed was a dose-related rhinorrhea that disappeared within 1 hour post exposure. There was no toxic effects of the combustion byproducts (CO, CO2, NO2and SO2), which remained below the threshold limit value. Under the conditions of this study, the acute LC50 of TPA was greater than 235 mg/m3 (analytical concentration).

In a further study (Leach et al, 1987), purified terephthalic acid was administered as a particulate aerosol by inhalation to a group of 5 male and 5 female Sprague-Dawley rats. The rats were exposed to an aerosol concentration of 2.02 mg/L. No rats died during the study. Therefore, the 2 hour acute inhalation LC50 of purified terephthalic acid was estimated to be greater than 2.02 mg/L. Gross necropsy revealed 1 male rat with dark lungs, and 1 male and 1 female rat with enlarged mandibular lymph nodes. No other abnormalities were detected. The 2 -hour LC50 was therefore >2.02 mg/L; a time-adjusted 4 -hour LC50 of >1 mg/L can therefore be derived.

A further study (ICI, 1987) is available only as a secondary source but reports no treatment-related effects in groups of 10 male rats exposed to terephthalic acid at target concentrations of 30, 100 or 1000 mg/m3; these findings are consistent with the results of the other studies.

Acute dermal toxicity study

Johnson et al (1990) applied the test substance isophthalic acid to the shaved back of 10 New Zealand albino rabbits (5/sex) at a dose level of 2 g/kg bw and was left in contact with the skin for 24 hours before being removed. No deaths occurred. Based on the results of this study, the dermal LD50 for isophthalic acid was determined to be greater than 2 g/kg bw.

Justification for classification or non-classification

Based on the results of the available studies, the substance is not classified for acute oral or dermal toxicity according to CLP Regulation EC No. 1272/2008. No data are available for acute inhalation toxicity, however low toxicity by this exposure route can also be predicted.