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Description of key information

In a sub-chronic oral toxicity study in rats, performed according to OECD guideline 408, NOAELs of 100 mg/kg bw/day for males and 500 mg/kg bw/day for females were established. In a sub-acute dermal toxicity study in rats, performed according to OECD guideline 410, NOAELs of 100 mg/kg bw/day (corresponding to 0.8 mg/cm2) for dermal irritation and 750 mg/kg bw/day (the highest dose tested) for systemic toxicity were established.

Key value for chemical safety assessment

Mode of Action Analysis / Human Relevance Framework

No information available.

Additional information

In a 90-day toxicity study (according to OECD guideline 408 and under GLP), Fischer 344 rats (10/sex/dose) were administered DIPA at 0, 100, 500 or 1000 mg/kg bw/day via their drinking water (Johnson, 2007). Additional groups (10/sex) were maintained on untreated water for an additional 28 days to assess recovery from DIPA-induced effects after initially receiving the control or high-dose water (0 or 1000 mg/kg bw/day) for at least 90 days. Rats given 1000 mg/kg bw/day drank less water than lower dose groups, with a corresponding decrement in food consumption and body weight. Urine specific gravity increased, and urine volume decreased for this group as well; both were considered to be related to reduced water intake. Serum cholesterol was slightly increased, and serum phosphorous was slightly decreased in the main study group at 1000 mg/kg bw/day; neither effect was noted in the recovery group. Changes in albumin in treated groups were also observed. Absolute and relative kidney weights were increased, males were affected to a larger degree. After the 28-day recovery, the changes in kidney weights were approximately one half that present at the end of the dosing period and slight renal tubule degeneration with regeneration was seen at the end of recovery in the 1000 mg/kg bw/day group. The only effect found in the 500 mg/kg bw/day group was increased absolute and relative kidney weights for males and females, without any histopathologic correlate. The mean relative kidney weights were increased about 12% and 7% relative to controls for males and females, respectively.Absolute kidney weights were increased in the 100 mg/kg bw/day male group, but these rats weighed more than the controls, and the relative kidney weights were not statistically different than controls. NOAELs of 100 and 500 mg/kg bw/day were established for males and females, respectively.

Rats (5/sex/dose) were dermally exposed to 0, 100, 500 or 750 mg/kg bw/day DIPA, 5 days/week for 28 days (according to OECD guideline 410 and GLP) (Johnson, 2007). Moderate erythema, edema with scabs, and hyperkeratosis were noted at the application site in animals treated with 500 and 750 mg/kg bw/day. No systemic toxicity was observed. NOAELs for dermal irritation and systemic toxicity of 100 mg/kg bw/day (corresponding to 0.8 mg/cm2) and 750 mg/kg bw/day were established, respectively. 

Justification for classification or non-classification

Based on the results of oral and dermal repeated dose toxicity studies, DIPA does not need to be classified according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.