1,1'-iminodipropan-2-ol

Endpoint summary

Key value for chemical safety assessment

Absorption rate - oral (%):

90

Absorption rate - dermal (%):

20

Absorption rate - inhalation (%):

100

Additional information

1. Physical-chemical properties

DIPA (MW: 133.2 g/mol) is a solid with a measured melting point of 44.5-45.5 °C, a measured boiling point of 248.8 -254.5 °C at 1013 hPa, a measured vapour pressure of 0.02 hPa at 20 °C, and a dissociation constant (pKa) of 9.05 at 20 °C. The octanol-water partition coefficient (log Pow) is -0.79 at 23 °C, and the substance is miscible in water at all proportions at 20 °C.

 

2. Data from acute and repeated dose toxicity studies

Acute toxicity data indicate low toxicity: in rats the oral LD50 was > 2000 mg/kg bw (BASF AG; 1993). In another study, an oral LD50 of 6000 mg/kg bw was established in rats. In animals of the highest dose group (i.e. 6400 mg/kg bw) a dilated stomach filled with black liquid and intestinal irritation were found at necropsy (BASF AG, 1965). A dermal LD50 of 8000 mg/kg bw was established in rabbits. Besides significant irritation at the site of application, congestion of lungs, livers, spleens and kidneys, mottled livers and opaque stomachs were observed at necropsy (Myers, 1997). Inhalation exposure for 8 hours to vapour saturated with DIPA did not cause any deaths in rats (BASF AG, 1965). Mice exposed to 500 – 2069 mg/m³ DIPA by inhalation for 3 hours, exhibited sensory and pulmonary irritation, with poor post-exposure recovery of the breathing frequency (Detwiler-Okabayashi, 1996).

 

In an oral repeated dose toxicity study, rats were administered 0, 100, 500 or 1000 mg/kg bw/day DIPA in their drinking water for 90 days. Decreases in food and water consumption and body weight were observed at the highest dose and were associated with increased specific gravity and decreased volume of the urine. Serum cholesterol was increased and serum phosphorous was decreased at the highest dose, which was no longer seen at the end of the 28-day recovery period. Absolute and relative kidney weights were increased at 500 and 1000 mg/kg bw/day without histopathological changes. The increased kidney weight was more pronounced in males than in females. The NOAELs were 100 mg/kg bw/day for males and 500 mg/kg bw/day for females (Johnson, 2007). The findings indicate that at high dose levels the kidney was the primary target organ. Effects on the kidney may be related to reduced water consumption. In a dermal repeated dose toxicity, rats were exposed to 0, 100, 500 or 750 mg/kg bw/day DIPA on the skin, 5 days/week for 28 days. Besides irritation at the site of application, no systemic toxicity was observed. NOAELs for dermal irritation and systemic toxicity of 100 and 750 mg/kg bw/day were established, respectively (Johnson, 2007).

 

3. Absorption, distribution, metabolism, excretion

The absorption, distribution and excretion of DIPA has been studied in rats after intravenous and dermal administration (Saghir, 2007). A single intravenous dose (19 mg ¹⁴C-DIPA/ kg bw) was administered to female rats and was followed by blood sampling at various time points. Following i.v. administration, DIPA was rapidly cleared from the plasma. Elimination occurred in a biexponential manner: a rapid initial phase and a slower terminal phase at t_1/2= 0.4 hours and t_1/2= 2.9 hours, respectively. The kidney was the main route of excretion with 71% of the DIPA excreted within 6 hours and 97% of the compound excreted unmetabolised in the urine within 48 hours. Active excretion by the kidney accounted for the rapid elimination. Dermal absorption was assessed with the same dose applied to the skin on the back of the rat for up to 48 hrs. DIPA was slowly absorbed through the skin; approximately 20% of the dose was absorbed. The steady state penetration rate was less than 0.3%/hour. Urinary excretion accounted for 14% of the radioactivity while fecal excretion was less than 0.2%. DIPA did not accumulate in the tissues as liver, kidneys, and carcasses accounted for less than 1% of the dose (Saghir, 2007).

No inhalation or oral absorption data are available for DIPA. For 2,4-dichlorophenoxyacetate, 1,1’,1’’-nitrilotripropan-2-ol salt (2,4 -D-TIPA) however, metabolism and excretion were assessed in an OECD TG 417 oral study in male rats, in which a single oral dose was administered, equivalent to 11.2 mg¹⁴C-TIPA/kg bw (Dow, 1992). Orally administered TIPA was rapidly and extensively absorbed by the rat. The principle route of excretion was urine, which contained 81-85% of the total dose, 3-5% was eliminated as ¹⁴CO2 and <2% was recovered in the tissues/carcass and final cage wash. The amount of ¹⁴C in the traps for volatile organics was negligible. Therefore, an oral absorption percentage of 90% is assumed for TIPA (feces contained 4-7%). Based on the available data for TIPA and on the small molecular size of DIPA, DIPA is expected to be rapidly and extensively absorbed upon oral exposure and rapidly excreted (mainly in the urine), without any bioaccumulation.