Bis(1,2,2,6,6-pentamethyl-4-piperidyl) [[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl]butylmalonate

Endpoint summary

Description of key information

The substance caused acute toxicity in rats with an LD50 of 1490 mg/kg bw. Morality occured with a delay of one to two weeks at the lower tested doses. No target organ could be identified upon necropsy. No adverse effects were observed in rats upon a single 24h occlusive application of 3100 mg/kg bw within the 2-week observation period. No adverse effects were observed after a 4h dust exposure to 0.49 mg/L during the 2-week observation period. All studies were performed prior existance of GLP and OECD testing guideline, but are comparable both in study design and reporting.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 490 mg/kg bw

Quality of whole database:

acceptable

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

460 mg/m³ air

Quality of whole database:

acceptable

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

3 170 mg/kg bw

Quality of whole database:

acceptable

Additional information

Acute oral toxicity was assessed by gavage dosing of 464, 1000, 1470, 1670, 2150 or 4640 mg/kg bw using 2% carboxymethylcellulose in water as vehicle(CIBA-GEIGY, 1976a). The study was performed prior to existence of OECD testing guidelines and GLP, but the procedure contains with the exception of body weight monitoring at termination all requirements of OECD testing guideline 401.

Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, exophthalmus, curved position and ruffled fur. Between the fourth and seventh day after intubation diarrhoea was also observed in animals of the four highest dosage groups.The surviving animals recovered within 9 to 14 days.

Mortality found in all dose groups except the lowest of 464 mg/kg bw. Mortality occurred during the second observation week at the low doses; higher doses caused an earlier onset. A specific target organ could not be identified from the available data.

 

 

Acute dermal toxicity was assessed by occlusive application of 2150 or 3170 mg/kg bw onto the back of rats for 24h (CIBA-GEIGY, 1976b). The study was performed prior to existence of OECD testing guidelines and GLP, but the procedure contains with the exception of body weight monitoring at termination all requirements of OECD testing guideline 402.

 No signs of local irritation or systemic toxicity were observed during the 14-day observation period. The LD50 is higher than 3170 mg/kg bw.

 

For assessment of acute inhalation, rats were exposed to aerosol in nose-only chambers for 4h (CIBA-GEIGY 1978a). The aerosol was generated by injecting the solid test material with the help of a "Grafix Exaktomat Injector" into an air stream which was discharged into the exposure chamber through a nozzle under a pressure of 2 atm. at a rate of 20 1/min.Under these conditions, 0.46 mg/L was the highest attainable concentration. The concentration was determined gravimetrically by sampling the test atmosphere through a selectron filter of 50 mm diameter and with a pore size of 0.2 µm (Schleicher and Schuell,,) at an air flow rate of 10 L/min. The size distribution of the particles was measured with a Cascade Impactor with selectron filters of 25 mm diameter and with a pore size of 0.2 µm (Schleicher and Schuell) at an air flow rate of 17.5 L/min. The following particle size distribution was determined: about 36.7% above 7 µm, about 34.4% between 3 and 7 µm, about 30% between 1 and 3 µm and about 1% less than 1 µm.

No symptoms were seen during the exposure and 14-day observation period. There was no effect on body weight. At necropsy no substance related gross organ changes were seen.

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

Justification for selection of acute toxicity – inhalation endpoint
Only study available

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

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for acute inhalation or dermal toxicity under Directive 67/548/EEC, as amended for the 28th time in Directive 2001/59/EC. Based on the LD50 of 1490 mg/kg bw, it is classified with Xn; R22.

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for acute inhalation or dermal toxicity under Regulation (EC) No. 1272/2008, as amended for the second time in Directive (EC 286/2011). Based on the LD50 of 1490 mg/kg bw, it is classified as category 4 for acute oral toxicity. A specific target organ for acute toxicity could not be identified from the experimental data.