Isophthalic acid

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Dose descriptor:

NOAEL

2 000 mg/kg bw/day

Additional information

In a modern, GLP- and guideline-compliant proprietary study (Milburn (2003), dietary administration of 20000 ppm terephthalic acid for two successive generations of Wistar-derived rats did not result in any effects on reproductive performance. No gross or microscopic changes were seen in the reproductive system that could be related to terephthalic acid administration. Irritant changes were observed in the bladder of males and females receiving 20000 ppm terephthalic acid and there was some evidence for an effect on the kidney at this dose level. These tissues were not examined for the 1000 or 5000 ppm groups. Reductions in pup bodyweight generally occurred from day 15 post partum, when the offspring had started consuming solid diet, and are considered to be a direct effect of the test material on the pups rather than an expression of developmental toxicity. Pup bodyweights in the F2 generation of the 20000 ppm treatment group were lower than control from parturition, but this is considered to be related to the larger litter size in this group. The only effect at a dose level of 1000 ppm was a decrease in kidney weight in adults and pups. The no observed adverse effect level (NOAEL) for effects on reproduction and development is therefore 20000 ppm, the highest dose used in this study.

The apparent effects on kidney weight seen in this study were considered by the independent UK Committee on Toxicity (COT). The COT used the criteria for distinguishing adverse from adaptive effects outlined in ECETOC Technical report No 85 (Recognition of, and Differentiation between, Adverse and Non-adverse Effects in Toxicology Studies). It was concluded that the effects on renal weight seen at 1000 ppm were without histopathological correlates and were concluded to be adpative effects. The COT therefore defined the NOAEL for toxicity as 5000 ppm (approximately 500 mg/kg bw/d).

Short description of key information:
No evidence of reproductive toxicity was seen in a modern two-generation study performed with the read-across substance terephthalic acid (TPA).

Effects on developmental toxicity

Description of key information

No evidence of developmental toxicity was seen at the highest exposure concentration of 9.07 mg/m³ in an inhalation study in the rat.

Effect on developmental toxicity: via inhalation route

Dose descriptor:

NOAEC

9.07 mg/m³

Additional information

In an inhalation study (Hatoum & Ryan, 1991), groups of 25 mated female Sprague-Dawley rats were exposed (whole-body) to atmospheres containing isophthalic acid at concentrations of 0, 0.98, 4.23 or 9.07 mg/m³ for 6 hours/day on ten consecutive days (Day 6-15 of exposure). Dams were observed daily for clinical signs and bodyweights measured at regular intervals. Dams were sacrificed of gestation Day 20 and the uterine contents examined. Foetuses were assessed for external, skeletal and visceral findings.

 

No deaths occurred and no signs of toxicity were observed during the study period. Litter parameters were comparable in all groups and no treatment-related increase in the incidence of foetal findings was apparent. The maternal and developmental NOAEC for this study is therefore 9.07 mg/m³. 

Justification for classification or non-classification

No evidence of reproductive toxicity was seen in a two-generation study performed with the read-across substance terephthalic acid at dose levels of up to 2000 mg/kg bw/d. No evidence of developmental toxicity was seen at the highest exposure concentration of 9.07 mg/m³ in an inhalation study with isophthalic acid performed in the rat. Based on the data available, classification for reproductive toxicity is not required for isophthalic acid under the CLP Regulation.