Registration Dossier

Administrative data

Description of key information

oral OECD 401, rat: LD50 = 1740 mg/kg bw
dermal OECD 402, rat (limit test): LD50 > 2000 mg/kg bw
inhalation OECD 403, rat, nose only, dust (limit test): LC50 > 5040 mg/m³

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 740 mg/kg bw
Quality of whole database:
The study was conducted according to the appropriate test guideline and in compliance with GLP (RL1).

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
5 040 mg/m³
Quality of whole database:
The study was conducted according to the appropriate test guideline and in compliance with GLP (RL1).

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
The study was conducted according to the appropriate test guideline and in compliance with GLP (RL1).

Additional information

One study is available addressing acute oral toxicity which was conducted with CAS No. 163520-33-0 according to OECD guideline 401 and GLP (Ehling, 1994a). 45 fasted Wistar rats (5/sex/group) received the test substance by oral gavage at a single dose of 625 (males only), 1250, 2000, 2500 and 5000 mg/kg body weight. The test substance was suspended in sesame oil. The mortality rates were comparable in both sexes. Lethality generally occurred between the 2nd and 6th day of the study, only one female animal died on day 14. The mortality rates were 0/5, 3/5, 2/5, 4/5 and 5/5 for the males and 1/5, 2/5, 4/5 and 5/5 for the females from the lowest to the highest dose group tested. Two males and one female at 2000 mg/kg were found dead and cannibalized. Clinical signs were nearly comparable in both sexes but they were more protracted in the females. They began to emerge 1 hour after administration and generally persisted up to Day 3 (males) or Day 14 (females) of the study. Nonspecific clinical signs comprised decreased spontaneous activity, drawn in flanks, stilted gait and squatting posture and were accompanied by irregular respiration, increased respiration rate, coat bristling and miosis. The body weight gains were only initially lowered in three female animals at 2000 mg/kg body weight, but they had returned to normal until the end of the study. Necropsy of the decedent animals revealed light discolouration and lobular demarcation of the liver, changes in the small intestine indicative for haemorrhages and red- or orange-discoloured lungs. The animals killed at the end of the experiment were free of macroscopically visible changes. Based on the mortality rates in this study the LD50 value was calculated by probit analysis for the male and female Wistar rat to be 1740 (1251 - 2245) mg/kg body weight.

One study from 1994 is available addressing acute dermal toxicity which was conducted with CAS No. 163520-33-0 according to OECD TG 402 and GLP (Ehling, 1994b). The study was conducted as limit test with a single dose of 2000 mg/kg bw applied to the dorsal area of the skin of 5 rats/sex under occlusive conditions for 24 hours. No mortality occurred in the dose group tested during the 15 days observation period. No treatment-related systemic clinical signs were observed in the animals and no local findings occurred which could be related to the test substance. Body weight gains were slightly impaired during the first week in two female animals only, which returned to normal up to the end of the study. The animals killed at the end of the experiment were free of macroscopically visible changes. Based on the results of this study the LD50 value for the male and female Wistar rat is greater than 2000 mg/kg body weight.

There is also one study available for acute inhalation toxicity, which was completed in 1998. The study followed GLP and was performed with CAS No. 163520-33-0 according to OECD guideline 403 (Blagden, 1998). In this study 5 rats/sex were nose-only exposed for a period of 4 hours to dust of the test substance (MMAD 1.7 µm) at a concentration of 5040 mg/m³ (limit test). No mortality ocurred within the 14-day observation period. Common clinical signs noted during the study were wet fur, hunched posture and pilo-erection. In some animals signs of increased or decreased respiratory rate, ptosis, red/brown staining around the eyes and snout and an isolated incident of laboured respiration were also noted. Animals recovered to appear normal one or two days after exposure. With the exception of one male which showed dark foci on the lungs, no abnormalities were detected at necropsy. This isolated finding was considered not to be related to treatment with the test material. The LC50 was determined to be higher than 5040 mg/m³ for exposure to dust of the test substance for 4 hours.


Justification for selection of acute toxicity – oral endpoint
The available reliable study was chosen as key.

Justification for selection of acute toxicity – inhalation endpoint
The available reliable study was chosen as key.

Justification for selection of acute toxicity – dermal endpoint
The available reliable study was chosen as key.

Justification for classification or non-classification

The available data on acute oral toxicity of the test substance meet the criteria for classification as Acute oral Category 4 (H302) according to Regulation (EC) 1272/2008 and as Xn (R22) according to Directive 67/548/EEC. The available data on acute dermal and inhalation toxicity of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.