Isophthalic acid

Endpoint summary

Additional information

Isophthalic acid (IPA) is only moderately soluble in water (ca. 120 mg/L at 25 degrees C, according to Park & Sheehan (1996), Roehrscheid (2005)) and this property limits the exposure concentrations of IPA that are achievable under the conditions of aquatic toxicity tests.

None of the uses of isophthalic acid involve direct application to surface water. The potential for unintended exposure of the aquatic compartment is therefore confined to IPA residues contained in treatment plant effluents discharged to surface waters. Moreover, it should be noted that production/manufacturing process effluents will be pH-balanced (neutralised) prior to treatment, to safeguard the treatment plant infrastructure from corrosion damage as well as to protect the biological purification process. Even without this deliberate intervention, IPA would rapidly be converted to isophthalate salts during treatment and/or in the aquatic environment. In terms of environmental exposure, the much more highly water-soluble isophthalate salts are therefore more relevant than the parent isophthalic acid.

No studies are available of the aquatic toxicity of IPA in the free acid form. However, reliable (Klimisch 1, guideline and GLP-compliant) studies address the short-term toxicity of terephthalic acid (TPA, benzene-1,4 -dicarboxylic acid), which is a structural analogue of IPA (benzene-1,3 -dicarboxylic acid), albeit with a lower aqueous solubility of ca. 17 mg/L at 25 degrees C. Both compounds comprise a single benzene ring with two carboxyl substituents. Since these substances differ only in the location of one of the two identical functional substituents, the read-across from terephthalic acid to isophthalic acid is considered justified. In these studies (Government of Japan, Ministry of the Environment, 2003a-c), aquatic organisms were exposed to high purity TPA (free acid), dosed from stock solutions prepared with DMSO, at a concentration intended to approximate to TPA's aqueous solubility limit. No toxicity was observed under these test conditions:

Himedaka (O. latipes) 96 -h LC50 (semi-static): >18.6 mg TPA/L, 96 -h NOEC: 18.6 mg TPA/L;

D. magna: 48 -h EC50 (semi-static): >20.1 mg TPA/L, 48 -h NOEC: 20.1 mg TPA/L;

P. kirchneriella: 72 -h ErC50 (static): >19.0 mg TPA/L, 72 -h NOErC: 19.0 mg TPA/L;

D. magna: 21 -d NOEC (semi-static): 19.5 mg TPA/L.

All these endpoints are mean measured values and all represent the highest or the single limit concentration achieved under the test conditions. They demonstrate an absence of toxicity at concentrations up to the limit of solubility of TPA in water at environmentally relevant temperatures.

Qualitatively, the same (i.e. no toxicity up to the limit of solubility) is considered to apply to the short-term toxicity of IPA in the free acid form, based on read-across. Support for this proposition is provided by three reliable (Klimisch 1, guideline- and GLP-compliant) short-term studies performed with IPA following neutralisation with NaOH solution and conversion to its more soluble sodium salt(s), which demonstrate the low intrinsic toxicity of the isophthalate moiety at nominal concentrations of up to 1000 mg/L.

In these studies (Knacker et al., 1993a-c), IPA was first treated with NaOH solution, to convert the acid to its much more soluble sodium salt(s), and exposure in these studies was consequently to sodium isophthalate (following neutralisation of excess alkali). No toxicity was observed under these conditions:

Golden orfe (L. idus melanotus) 96 -h LC50 (static): >907 mg Na2IPA/L, 96 -h NOEC: 907 mg Na2IPA/L;

D. magna 48 -h EC50 (static): >952 mg Na2IPA/L, 48 -h NOEC: 952 mg Na2IPA/L;

D. subspicatus 72 -h ErC50: >996 mg Na2IPA/L, 72 -h NOEC: 996 mg Na2IPA/L.

All these endpoints are mean measured values and represent the highest concentration applied.

Additionally, a reliable (Klimisch 1, guideline and GLP-compliant) study addresses the long-term toxicity of terephthalic acid (TPA) to aquatic invertebrates. In this study (Government of Japan, Ministry of the Environment, 2003d), D. magna were exposed to high purity TPA (free acid), dosed from stock solutions prepared with DMSO, at a concentration intended to approximate to TPA's aqueous solubility limit. No toxicity (adult mortality or adverse impact on reproduction or growth) was observed under these test conditions:

D. magna: 21 -d NOEC (semi-static): 19.5 mg TPA/L.

This endpoint is a mean measured value and demonstrates an absence of long-term toxicity to aquatic invertebrates at concentrations up to the limit of solubility of TPA in water. By applying read-across based on close structural similarity, it is reasonable to suppose that the corresponding endpoint for isophthalic acid is at least similar to that of TPA (NOEC >/= ca. 20 mg/L), but since no relevant data are available for IPA or its salts it is uncertain whether the no-effect range extends as far as IPA's aqueous solubility limit (ca. 120 mg/L at 25 degrees C).

In conclusion, isophthalic acid and its more environmentally relevant isophthalate salts exhibit very low toxicity to fish, aquatic invertebrates and unicellular algae.

In a reliable (Klimisch 1, guideline- and GLP-compliant) study of the toxicity of isophthalic acid to aquatic microorganisms (Lebertz, 1991), the 3 -h EC50, based on inhibition of respiration of activated sludge, was 617.1 mg/L. Inhibition, relative to the untreated control, was observed at all concentrations applied (>/= 500 mg/L) and the EC5 (the calculated effect threshold) was 158.3 mg/L. All the nominal concentrations applied exceeded the water-solubility of the test substance, although it is likely that some more highly soluble isophthalate salts were formed by interaction between the acid and the mineral constituents of the synthetic sewage present in the test system. No pH measurements were reported; consequently it is uncertain to what degree a lowering of pH may have caused or contributed to the observed effect.

Nevertheless, it may be concluded that isophthalic acid presents low toxicity to aquatic microorganisms and to biological waste water treatment systems.