Registration Dossier

Administrative data

Description of key information

Acute toxicity: oral:
A K1 acute oral toxicity test was performed in female Sprague Dawley rats according to a guideline similar to OECD Guideline 425 and EPA OPPTS 870.1100 (Lemoncelli, 2012). The LD50 for the oral route was determined to be 550 mg/kg bw (88.94 - 2340 mg/kg, 95% CL).
Acute toxicity: inhalation
An acute inhalation study does not need to be conducted as the substance is classified as corrosive to the skin (according to REACH, Annex VIII section 8.5, column 2). In addition, acute oral and acute dermal toxicity studies are available.
Acute toxicity: dermal
A K1 acute dermal toxicity test was performed in male and female Sprague-Dawley rats according to a guideline similar to OECD Guideline 402 and EU Method B.3 (Lemoncelli, 2012). The LD50 for the dermal route was determined to be > 1000 and < 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
550 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed

Additional information

Acute toxicity: oral

Lemoncelli (2012) investigated the acute oral toxicity via gavage of 175, 550 and 2000 mg/kg bw Jeffamine RFD 270 in female Sprague-Dawley rats (6 rats in total: 2 in the 175 mg/kg dose group, 3 in the 550 mg/kg dose group and 1 in the 2000 mg/kg dose group). At 175 mg/kg no mortality was observed; at 550 mg/kg two of three animals receiving the test article were found dead and at 2000 mg/kg the single animal was as well found dead. The acute oral LD50 for male and female rats treated with Jeffamine RFD 270 was determined to be 550 mg/kg with confidence limits of 88.94 to 2430 mg/kg. No clinical signs were observed at 175 mg/kg or in the initial surviving animal at 550 mg/kg. Abnormal gait and stance, decreased activity, and decreased body tone were observed in the animal at 2000 mg/kg. In addition to these signs piloerection was observed in one animal at 550 mg/kg prior to death. Terminal necropsy revealed no visible lesions in the surviving animals at 175 and 550 mg/kg. Necropsy of the animals found dead revealed lesions of the intestines and stomach including fluid-filled red, lining red and a dark red circular lesion.

Acute toxicity: inhalation

No reliable studies were available for the inhalation route. An acute inhalation study does not need to be conducted as the substance is classified as corrosive to the skin (Regulation (EC) No 1907/2006, Annex VIII section 8.5). In addition, acute oral and acute dermal toxicity studies are available.

Acute toxicity: dermal

Lemoncelli (2012) investigated acute dermal toxicity of Jeffamine RFD 270 in male and female Sprague-Dawley rats (5 animals per sex and per dose) after 24 hours of exposure to either 50, 200, and 1000 mg/kg bw in the full definitive test. One group of ten animals (5/sex) received the test article at 2000 mg/kg. After 14 days of observation, the dermal LD50 for Jeffamine RFD 270 was > 1000 mg/kg. No mortality was observed at 50 or 200 mg/kg. Nine of ten animals were found dead at 2000 mg/kg and one of ten were found dead at 1000 mg/kg.

All animals at 50 mg/kg were observed to be clinically normal without signs of dermal irritation throughout the study. At 2000 mg/kg, all ten animals exhibited signs of irritation and necrosis at the application site by day 2 with clinical observations. The one remaining animal in this group continued with irritation and necrosis and was clinically normal at day 14. At 200 mg/kg, irritation was observed in four animals starting on day 2 with full resolution by day 6. Clinical observations were present in one animal at 200 mg/kg on day 2 only. At 1000 mg/kg, irritation was observed starting on day 2 in eight animals with necrosis beginning in three of ten animals on day 4. Irritation almost completely resolved in the remaining animals by day 15. Clinical observations were present in five animals at 1000 mg/kg on day 2 only.

No visible lesions were observed in the animals at terminal necropsy. Necropsy of found dead animals revealed: fluid filled stomachs in four of eight animals found dead in the 2000 mg/kg group on day 3 as well as dark red intestines in one animal found dead on day 4. Necropsy of the found dead animal in the 1000 mg/kg group on day 3 revealed dark red intestines.


Justification for selection of acute toxicity – oral endpoint
Only one reliable study available

Justification for selection of acute toxicity – inhalation endpoint
No reliable studies were available for the inhalation route. An acute inhalation study does not need to be conducted as the substance is classified as corrosive to the skin (Regulation (EC) No 1907/2006, Annex VIII section 8.5). In addition, acute oral and acute dermal toxicity studies are available.

Justification for selection of acute toxicity – dermal endpoint
Only one reliable study available

Justification for classification or non-classification

Based on the results of the acute oral and acute dermal toxicity study and according to the criteria of the DSD and CLP Regulation, Jeffamine RFD 270 should be classified with R21 and R22 (DSD) and as an acute oral and acute dermal toxicant category 4, H302 and H312 (CLP)