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Administrative data

Description of key information

The acute oral LD50 of the substance was found to be >15380 mg/kg bw in the rat.  The acute inhalation toxicity is also low, with a 2-hour LC50 of >2.02 mg/L.  Low acute dermal toxicity indicated in a limit test in rabbits.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
15 380 mg/kg bw
Quality of whole database:
One proprietary study is available for acute oral toxicity. The study pre-dates GLP and the OECD guideline, but is comparable to OECD 401 and considered to be sufficiently reliable for the purposes of hazard classification.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
2 020 mg/m³
Quality of whole database:
A guideline-comparable study is supported by less reliable data.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Reliable, guideline-compliant study

Additional information

Acute oral toxicity

A guideline-comparable study (Harrison, 1975) is available, in which terephthalic acid in corn oil was administered orally by gavage to male and female rats at dose levels of 6834, 10250 and 15380 mg/kg bw. Rats were observed for 14 days following administration. The only deaths that occurred were in the mid dose group (10250 mg/kg bw); 1 female died within 22 hours of administration, and 1 male died on day 3. Gross necropsy revealed that these rats had pale discoloured kidneys. Clinical signs observed at all dose levels included hypoactivity, piloerection, diarrhoea, muscular weakness and rhinitis. Minimal transient weight loss was observed in individual animals; however there were no effects on body weight gain over the 14-day study period. Gross necropsy of all animals surviving to the end of the 14-day observation period did not reveal any abnormalities. The acute oral LD50 of terephthalic acid in the rat is therefore shown to be >15380 mg/kg bw under the conditions of this study. Terepthalic acid is therefore of very low acute oral toxicity.

Acute inhalation toxicity

In the key 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 (whole body) to an aerosol concentration of 2.02 mg/L for two hours; the exposure period was terminated due to an accumulation of the test material. 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 >1.01 mg/L can therefore be derived.

In a further 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 disapeared within 1 hour post exposure. There was no toxic effects of the combustion byproducts (CO, CO2, NO2 and 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).

A further study (ICI, 1987) is available only as a secondary source but reports no treatmnet-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.

While the studies of acute inhalation toxicity available for terephthalic acid have some deficiencies, they are consistent in demonstrating low toxicity by this route of exposure.

Acute dermal toxicity

The acute dermal toxicity of the substance in the rabbit was investigated by Lord (1990) in a limit test, with five male and five female New Zealand White rabbits. The test material was placed in contact with the shaved pre-moistened skin of the rabbits, under an occlusive dressing, for 24 hours. The rabbits were observed during this time and for 14 days thereafter. No deaths occurred during the study. Mild dermal irritation (erythema) was observed within the application site of six rabbits immediately following unwrapping. Otherwise, no adverse treatment-related clinical signs were observed in any rabbits during the study. Mean body weights increased during the study. No gross pathological lesions attributable to treatment were evident in any of the rabbits at necropsy. The acute dermal LD50 of terephthalic acid was found to be greater than 2000 mg/kg bw under the conditions of this study.


Justification for selection of acute toxicity – oral endpoint
Only study available for this endpoint

Justification for selection of acute toxicity – inhalation endpoint
Guideline-comparable study

Justification for selection of acute toxicity – dermal endpoint
Only study available for this endpoint

Justification for classification or non-classification

No classification for acute toxicity is proposed on the basis of the acute oral and dermal toxicity studies. The available data also demonstrate low acute inhalation toxicity and indicate that the substance would not be classified for acute inhalation toxicity. Although the available inhalation toxicity studies use exposure periods shorter than the standard 4 hours and/or lower maximum exposure concentrations than the limits for classification, no further inhalation toxicity testing is proposed. It can be reliably assumed, based on the available lack of effects at exposure concentration of approximately 1 and 2 mg/L that the inhalation LC50 of the substance will be below the limit for classification of 5 mg/L. Additional testing is not considered to be appropriate on scientific grounds and for reasons of animal welfare.

No classification for acute toxicity is therefore proposed, according to the CLP Regulation.