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Description of key information

Acute oral toxicity:
2 Weight of Evidence (WoE) tests: Acute toxic class method (no guideline followed): LD50 > 15800 and LD50 > 7940 mg/kg bw (male/female rat).
Acute dermal toxicity:
Standard acute method, Limit test (similar to OECD 402): LD50 > 2010 mg/kg bw (male/female rabbit).
Acute inhalation toxicity:
Standard acute method, Limit test (similar to OECD 403): LC0, 4h = 6.3 mg/L air (analytical) (aerosol; male/female rat).

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
7 940 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50
Value:
6 300 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
Value:
2 010 mg/kg bw

Additional information

The only 2 available studies for acute oral toxicity of IDDPP were chosen as Weight of Evidence studies, as they were concise, and not performed according to methods similar to an existing guideline, but together provide sufficient information. In one range finding study the undiluted compound was fed by stomach tube to male and female rats (total 11 animals) in increasing doses (1000, 2000, 3160, 5010, 7940, 12600, and 15800 mg/kg bw). Toxic symptoms included slight weakness in animals dosed at the two highest levels (12600 and 15800 mg/kg) for 3 to 4 days. No mortality occurred. The highest dose of 15800 mg/kg was found to be non-lethal in 5 rats, observed over a period of 9 days. The oral LD50 of IDDPP is therefore > 15800 mg/kg bw in this study. In the other, more recent, acute oral toxicity study the undiluted compound was fed to 25 male and female rats (5 rats/dose) in increasing doses (6310, 7940, 10000, 12600, and 15800 mg/kg). Observations were made for toxic signs during 14 days, surviving animals were sacrificed, and the viscera of the test animals were examined macroscopically. Gross autopsy was performed on decedents. Signs of intoxication were reduced appetite and activity (1 to 3 days in survivors), increasing weakness, collapse, and death. Deaths were observed at 10000 mg/kg (2 females), 12600 mg/kg (3 females), and 15800 mg/kg (2 females), at 1 to 4 days. Gross autopsy of decedents revealed hemorrhagic areas of the lungs, liver hyperemia and gastrointestinal inflammation. In survivors (14 days) the viscera appeared normal. Based on mortality in the three highest doses, which was not sufficient to derive an LD50 value, an LD50 of > 7940 mg/kg bw was set.

In the available key acute dermal toxicity test of IDDPP was administered undiluted in a single dose of 2010 mg/kg on the lightly abraded skin of 5 male and 5 female rabbits, and then occluded for 24 hours. The rabbits were observed during 14 days. There were no deaths during the study. The average skin erythema and edema scores at 24 hours were 1.4 and 0.4 resp. The animals gained weight in a normal manner. No observable abnormalities in any of the animals at gross pathology examination. The acute dermal LD50 for IDDPP as indicated by the data in this study is > 2010 mg/kg. One supporting study, being a rather short abstract, was available for acute dermal toxicity, not performed according to a method similar to an OECD guideline. Two doses (5010 and 7940 mg/kg) were applied for 24 hours to 3 animals (2 (M+F) and 1 (M) per dose). Observations were made for toxic signs during 14 days, surviving animals were sacrificed, and the viscera of the test animals were examined macroscopically. No mortality occurred. Signs of intoxication were reduced appetite and activity for 4 to 7 days. In the survivors (14 days) viscera appeared normal. The dermal LD50 of IDDPP was established > 7940 mg/kg bw.

The key acute inhalation toxicity study in rats was performed under early GLP. A single 4-hour exposure to 6.3 mg/L IDDPP as a respirable aerosol mixture produced no mortality in a group of 5 male and 5 female rats. Rats were observed for 14 days after exposure. Signs exhibited during exposure included increases in secretory responses and reduced activity. Signs during the post-exposure period: incidences of secretory responses, rough coat and yellow ano-genital fur. A transient decrease in body weight was observed. As no deaths occurred the tested concentration can be considered as LC0 and the LC50>6.3 mg/L. Two supporting studies were available, both performed to a method similar to OECD 403, but not under GLP and with deviating exposure times and number of animals tested. In one study 4 male rats were exposed for 6 hours at the heated sample test (162.7 °C) of IDDPP at a calculated concentration of 1.74 mg/l (vapour). All animals survived the 6 hour exposure, but all succumbed in 3 to 4 days following exposure. The LC100, 6h was calculated to be 1.74 mg/l (nominal concentration). In the other supporting study a 1-hour acute inhalation exposure to an aerosol of IDDPP at a nominal concentration of 100.2 mg/l did not produce mortality in 5 male and 5 female rats, but caused slight reversible irritation of the ocular, nasal, and buccal mucous membranes in both sexes and slight residual pulmonary changes evident at necropsy in males only. As no deaths occurred the tested concentration can be considered as LC0(1h).

Justification for classification or non-classification

For acute oral toxicity, the LD50 value (for both male and female rats) was found to be at least > 7940 mg/kg bw in both WoE studies. Based on this value and the criteria outlined in Annex I of 1272/2008/EC and Annex VI of 67/548/EEC, the substance IDDPP does not need to be classified for acute oral toxicity.

For acute dermal toxicity, the LD50 value of > 2010 mg/kg bw (male/female rabbits, 24 h.) was used for classification. Based on this value and the criteria outlined in Annex I of 1272/2008/EC and Annex VI of 67/548/EEC, IDDPP does not need to be classified for acute dermal toxicity.

For acute inhalation toxicity, the LC50 value of > 6.3 mg/l for 6 h. was used for classification. Based on this value and according to the EU criteria outlined in 67/548/EEC and 1272/2008/EC (CLP/EU-GHS) IDDPP does not need to be classified and has no obligatory labelling requirement for inhalation toxicity.