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Description of key information

Oral 90-d repeated dose toxicity study: LOAEL 10 mg/kg bw/day

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
LOAEL
10 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The key study was a 90-day repeated dose toxicity oral feeding study, which was performed equivalent or similar to OECD408. Male and female rats were exposed to 0, 140, 1400, and 7000 ppm incorporated in the diet, resulting in doses of 0, 10, 100, and 500 mg/kg/bw/day. Rats were observed for mortality and clinical signs twice daily. Furthermore, body weight and food consumption was determined weekly. Haematology, clinical chemstry and urinalysis were measured at an interim measurement (6 -7 weeks) ant at termination (13 -24 weeks). Gross necropsy was performed animals from all doses, histopathology on animals from the control and high dose group.

Observed effects were reduced body weight gain, reduced food consumption, alterations in numbers of circulating red blood cells and red blood cell indices, decreased white blood cell values, decreased creatinine and serum glutamic oxaloacetic transaminae (SGOT), increased gamma glutamyl transpeptidase (gamma-GT), urobilinogen, urine bilirubin, cholesterol and phosphorus levels, as well as increased liver weights and hepatocellular hypertrophy/hyperplasia and hepatocellular brown pigment. As the effects on haematology parameters occurred at the lowest dose level, it was not possible to derive a NOAEL. The LOAEL was 140 ppm or 10 mg/kg bw/day.

A supporting 28 -day repeated dose toxicity oral feeding study was available in which Sprague-Dawley rats were exposed to IDDPP via the food. Tested dose levels were 0, 250, 500, 750, 1000, and 2000 mg/kg bw/day. Mortality, body weight, food consumption, and clinical signs were examined. After exposure, all animals were necropsied and gross pathology was performed.

Decrease in body weight gain in combination with decreased food consumption was observed in males in the three highest dose groups and in high dose females. No treatment-related deaths or clinical signs were observed. Hepatic enlargement and/or violet discoloration occurred in both males and females, but no statistics was performed to determine statistical significance.Therefore, no NOAEL could be established.


Repeated dose toxicity: via oral route - systemic effects (target organ) cardiovascular / hematological: other

Justification for classification or non-classification

Based on the available information, no decision can be made concerning the classification of IDDPP.