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Description of key information

A repeat dose (31-day) oral toxicity study in feed was conducted in rats at dose levels of 93 and 239 mg/kg/day.  The NOAEL was deemed to be 239 mg/kg/day based on the lack of effects reported at dose.  A high quality 28 day dermal toxicity study and a high quality 90 day dermal toxicity study are available.  In the 90-day dermal study, no systemic toxicity was observed at the highest dose level of 250 mg/kg/day. Therefore, the NOAEL for systemic toxicity was determined to be 250 mg/kg/day.  However, significant irritation was observed in the high dose group.  Therefore, the NOAEL for local effects was deemed to be 80 mg/kg.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
239 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 adverse effect observed
Dose descriptor:
NOAEL
250 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
80
Study duration:
subchronic
Species:
rat

Additional information

A long-term, 31 day oral toxicity feeding study in rats was conducted on POPDA. The substance was incorporated into the diet to give final concentrations of 0.083% and 0.208% and fed to groups of 5 males and 5 females for 31 days. There were no deaths and no relevant gross pathology noted in either sex at autopsy. A subacute, preliminary dose range finding study was performed in rabbits with POPDA administered via oral gavage at single occasion at 300 and 600 mg/kg, or daily for 11 days at 300 mg/kg. Dose levels of 300 mg/kg were unsuitable for repeat dosing in rabbit and lead to marked findings in stomach and GI tract. A high dose of 150 mg/kg/day was recommended in a subsequent embryo-fetal development study.

A 28 -day dermal toxicity study was conducted in methods comparable to OECD guideline 410. Groups of 5 male and 5 female rats were exposed to POPDA 6 hours/day, 5days/week for 4 weeks at 50, 100, 250, 500, and 750 mg/kg. Clinical signs observed in the 250, 500, and 750 mg/kg dose groups were very slight to well-defined erythema, very slight to severe edema, fissuring of skin, sloughing of skin and necrosis of the dose area. Terminal necropsy revealed mottled lungs, red foci throughout the lungs, yellow discoloration of the left lateral lobe of the liver, tan foci on the medial lobe of the liver and mottled kidneys in the test substance treated groups.

Based on the results of the 28 -day study, 50, 80, and 250 mg/kg were used in the 90 -day dermal study.

In a repeat dose toxicity study, the substance was applied dermally to rats 6 hours/day, 5 days per week, for 90 days with a 28-day recovery period at doses of 0, 50, 80, and 250 mg/kg. No systemic effects were reported at any dose. Therefore, the NOAEL for systemic effects was deemed to be 250 mg/kg. However, significant irritation was observed in the high dose group. Therefore, the NOAEL for local effects was deemed to be 80 mg/kg.

Justification for classification or non-classification

The NOAEL for systemic toxicity was equal to or greater than 250 mg/kg in the 90-day dermal toxicity study. Because the cut off value for category 2 specific target organ toxicity repeated exposure - dermal is 20-200 mg/kg/day, no classification is justified for POPDA.