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Description of key information

The acute oral toxicity of CS-1246 is low with LD50 levels in male and female rats at 5249 mg/kg (4503-6673 mg/kg), and 3674 mg/kg (3216-4197 mg/kg) respectively. 
The acute dermal toxicity in the rat is therefore greater than 2,000 mg/kg. In an acute dermal toxicity study in the rabbit with abraded skin the dermal LD50 was 1948 mg/kg (1596-18495 mg/kg). The acute dermal study in rat is considered to be the key study for this enpoint as it meets current protocol guidelines and is conducted to GLP.
The acute inhalation LC50 was calculated to be 3.1 mg/L (95% CI, 2.7-3.5 mg/L)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
3 674 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50
3.1 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50

Additional information

To assess the acute oral toxicity of CS-1246 rats (10/sex/group) were treated by oral gavage at doses 0, 2,100, 3000, 4,200 or 6,000 mg/kg (Parekh, C. 1980) Animals were observed frequently on the day of dosing, and daily thereafter for 14 days. Any unusual signs of toxicity or death were noted. Animals were subjected to a gross pathological examination as soon as possible after spontaneous death, or at the scheduled necropsy on day 14. The acute oral toxicity of CS-1246 is low with LD50levels in male and female rats at 5249 mg/kg (4503-6673 mg/kg), and 3674 mg/kg (3216-4197 mg/kg) respectively.

The acute dermal toxicity of CS-1246 was tested in 5 male and 5 female Wistar rats at a dose of 2000 mg/kg body weight (Ravi, G. S. (2009)). All rats gained body weight through the observation period. No local skin reactions were observed. No pre-terminal deaths occurred and no abnormalities were detected at necropsy. The acute dermal toxicity in the rat is therefore greater than 2,000 mg/kg. In an acute dermal toxicity study in the rabbit with abraded skin the dermal LD50was 1948 mg/kg (1596-18495 mg/kg).

For the acute inhalation study rats, (5 male and 5 female per treatment group), were exposed (whole-body) to aerosols of CS-1246, (particle size distributions ranged from 3.9-4.7 microns MMAD), to give exposure concentrations of 0, 1.6, 2.4, 2.6, 3.3 or 4.5 mg/litre (Terrill, J.B. and Hogan, G.K., 1982). All test material-dependent deaths occurred on the day of or the day after exposure. In the absence indications of systemic injury, the rapid death suggests severe irritation/injury to the respiratory tract. Histopathological examination of the lungs of the lungs of all rats failed to show treatment-related pulmonary injury. This suggests irritation/injury to the upper respiratory tract, however, no examination of the nasal airways was conducted. The acute inhalation LC50 was calculated to be 3.1 mg/L (95% CI, 2.7-3.5 mg/L).

References:

Parekh, C. (1980) Acute Toxicity Profile of P-1601 (Oxazolidine E). 

International Minerals and Chemicals Corp. The Dow Chemical Company Report No: DR-0365-7725-001. Not GLP, Unpublished

Ravi, G. S. (2009) BIOBAN CS-1246: Acute Dermal Toxicity Study in Rats. 

Advinus Therateutics Private Limited. Bangolore, Study No. G6693.
The Dow Chemical Company Report No: DR-0365-7827-016. GLP, Unpublished

Terrill, J.B. and Hogan, G.K. (1982) An Acute Inhalation Toxicity Study of ZOLDINE ZE (P-1601) in the Rat. BIODYNAMICS Inc. The Dow Chemical Company Report No: DR-0365-7725-002 Not GLP, Unpublished

Justification for classification or non-classification

Based on the oral and dermal LD50 values above 2000 mg/kg/day, classification for acute toxicity via these routes are not warranted according both EU Directive 67/548/EEC and CLP Regulation (EC) No. 1272/2008.

Based on the inhalation LC50 value, classification for acute toxicity via the inhalation route of exposure is Xn R20 according to EU Directive 67/548/EEC and Cat 4 acute tox H332 (Harmful if inhaled) according to CLP Regulation (EC) No. 1272/2008.