Isophthalic acid

Endpoint summary

Description of key information

The substance was found to be of low toxicity in a 90-day dietary rat study and in a 28-day rat inhalation study.  Effects in the dietary study were limited to urolithiasis and secondary effects; findings were more marked in males.  No clear or significant effects of treatment were seen in the inhalation study.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

LOAEL

500 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEC

9.59 mg/m³

Study duration:

subacute

Species:

rat

Additional information

Repeated dose oral toxicity

In a sub-chronic study (Vogin, 1972), groups of rats (25/sex) were administered isophthalic acid (IPA) in the diet at dose levels of 0.5, 1.6 and 3% for up to 90 days. The highest dose level was reduced to 3% after one week due to effects on bodyweight. Animals were observed for mortality and clinical signs; bodyweights were recorded at intervals. Blood samples were taken for the assessment of clinical chemistry and haematological parameters; urinalysis was also performed. Animals were investigated at necropsy (30, 60 and 90 days) for gross and microscopic findings; organ weights were also recorded. Blood levels of phthalates were also investigated.

No deaths occured and there were no signs of toxicity. Bodyweights were markedly reduced at the highest dose level of 3% (initially 5%). No effects were seen on haematological and clinical chemistry parameters; urinalysis revealed the presence of red blood cells and crystals in the urine of treated animals. Findings were associated with increased kidney weights but did not have any gross or microscopic pathological correlates. A LOAEL of 0.5% (5000 ppm, equivalent to 500 mg/kg bw/d) can be determined for male rats in this study, based on the incidence of bladder/kidney stones in all treated groups. A LOAEL of 1.6% (16000 ppm, equivalent to 1600 mg/kg bw/d) can be determined for female rats in this study based on the incidence of bladder stones, bodyweight effects and kidney weight effects at the highest dose level.

Repeated inhalation toxicity

Ledbetter et al (1988) administered isophthalic acid as a particulate aerosol by inhalation at target concentrations of 1.0, 5.0 and 10.0 mg/m3 to three groups of 10 male and 10 female rats each. A fourth group of an equal size, was exposed to filtered air only and served as a control. The rats were exposed for 6 hours/day, 5 days per week for four weeks. In addition, 5 rats/sex designated for pre-exposure, single exposure and weekly serum analysis for IPA were included in the control and high exposure groups. These rats were retained for 3 weeks after the last exposure to monitor diminishing levels of IPA and to evaluate recovery from IPA-induced effects. IPA was detected in the serum of high exposure rats immediatley after the first exposure and remained elevated for the duration of the exposure. One week after the last exposure, no IPA was detected in the serum of any exposed rat. No clearly treatment-related effects of toxicological significance were seen in this study; a NOAEC of 9.59 mg/m3 is therefore derived.

Repeated dose toxicity: via oral route - systemic effects (target organ) urogenital: kidneys; urogenital: urinary bladder

Justification for classification or non-classification

The available studies do not indicate any marked toxicity or effects at relevant dose levels. No classification for repeated dose toxicity is therefore proposed for the substance according to the CLP Regulation EC Number 1272/2008.