Registration Dossier

Administrative data

Description of key information

The acute oral toxicity of IPPD is moderate, indicated by an oral LD50 value of 522 mg/kg for males and 701 mg/kg bw for females rats (Hatano Research Institute 2003). This finding is supported by an earlier oral toxicity study (Monsanto Co. 1974). Based on these findings IPPD is classified as harmful if smallowed; in consequence, existing classification with R22/ acute toxicity category 4 is confirmed.
The acute dermal toxicity of IPPD is low, indicated by a dermal LD50 value of > 7940 mg/kg bw in rabbits after single application (Monsanto Co. 1973).

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
522 mg/kg bw

Acute toxicity: via dermal route

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

Additional information

Oral:

The acute oral toxicity of IPPD was evaluated in a GLP and OECD guideline study (TG 401) (Hatano Research Institute 2003). In this OECD study 5 male and 5 female rats were dosed with 0, 269, 350, 455, 592, 769 and 1000 mg/kg bw in sodium carboxymethylcellulose (0.5 %) by gavage. Deaths occurred at day 2 to 4 after the treatment with 269 mg/kg and above in males and 592 mg/kg bw and above in females. Clinical signs like prone position, lacrimation, hypothermia and reduced respiration were observed. Pathological evaluations of decedents revealed enlargement of the liver, enlargement and pale coloration of the kidney, pleural effusion, ascites, edematous lung, shrinking and pale coloration of the spleen, detachment or red colored areas in the forestomach muscosa, thickening and pale coloration in the mucosa of glandular stomach and yellowish colored change of the subcutis. In animals, which were scheduled sacrificed; thickening and pale coloration in the mucosa of forestomach was observed. Histological evaluations in decedents revealed necrosis or degeneration of centrilobular hepatocytes and hypertrophy of hepatocytes, necrosis or degeneration in the proximal tubular epithelium of the kidneys, alveolar edema in the lung, hemorrhage and edema in the submucosa of the forestomach and in the mucosa of glandular stomach. In sacrificed animals hypertrophy of centrilobular hepatocytes, increased mitosis of hepatocytes and regeneration in the tubular epithelium of kidney were noted. Some of these animals showed cellular infiltration of foam cells and neutrophils in the lung, brown pigment deposition in the forestomach and regeneration in the epithelium of the glandular stomach.

Based on findings from this study an oral LD 50 value of 522 mg/kg for males and 701 mg/kg bw for females were calculated.

In an earlier acute oral toxicity study with rats an oral LD50 value of 900 mg/kg bw was calculated (Monsanto Co 1974). Death occurred at 794 mg/kg bw and higher one to five days after test substance application. Clinical signs were observed and included reduced appetite and activity (lasting 3 to 5 days in survivors), increasing weakness, collapse and death. Autopsy of decedents showed lung hyperemia, slight liver discoloration, and acute gastrointestinal inflammation. Viscera of survivors appeared normal.

Dermal:

The acute dermal toxicity of the test substance IPPD was evaluated in acute dermal toxicity study with New Zealand albino rabbits (Monsanto Co. 1974). Test substance was applied as a 40 % solution-suspension in corn oil for 24 hours directly to the clipped, intact skin of New Zealand albino rabbits (1 to 2 animals per dose) at doses of 5010 and 7940 mg/kg bw. No mortality occurred during the study. Clinical signs were observed and included reduced appetite and activity for three to five days. Based on these findings a dermal LD50 of >7940 is suggested.

Justification for classification or non-classification

The test substance IPPD is classified as harmful if swallowed ( Acute Tox. 4; H302) according to regulation no. 1272/2008 (GHS).