1,1'-{(phenylmethanediyl)bis[(3-substituted benzene-4,1-diyl)diazene-2,1-diyl{1-[3-(dimethylamino)propyl]-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridine-5,3-diyl}]}dipyridinium chloride lactate salts

Endpoint summary

Description of key information

Acute toxicity:
Oral rat (Acute toxic class method):  discriminating dose: 50 mg*/kg bw: 100% survival but evident toxicity;
High mortality at 300* mg/kg (67% mortality) and 2000 mg*/kg (100% mortality).
Classification:
"harmful (Xn)" and  "harmful if swallowed (R22)" [DIRECTIVE 67/548/EEC] and
"Category 3 (Danger, Toxic if swallowed)" [REGULATION (EC) 1272/2008].
Dermal rat: LD50 > 2000 mg*/kg bw  (10% mortality at 2000 mg*/kg bw)
Classification: No labelling requirement regarding acute dermal toxicity [DIRECTIVE 67/548/EEC and Reg. (EC) 1272/2008]
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* Expressed as water- and minor impurity-free test substance

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

discriminating dose

Value:

50 mg/kg bw

Acute toxicity: via dermal route

Endpoint conclusion

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

The acute oral toxicity study demonstrated that the respective LD50 of the test substance is slightly lower than 300* mg/kg indicating some oral toxicity.

The acute dermal toxicity study demonstrated that the respective LD50 of the test substance is higher than the limit dose of 2000* mg/kg b.w. Therefore, the test material is considered to be relatively harmless regarding acute dermal toxicity. It cannot be ruled out that the clinical signs seen in all survivors and the single death were caused by oral uptake (grooming behaviour) of residual test material after patch removal, since dermal absorption/toxicity of the test material seems rather unlikely, because of its high molecular weight.

 

According to EU classification rules [DIRECTIVE 67/548/EEC and REGULATION (EC) 1272/2008] the results attained in this study do not necessitate any labelling regarding acute dermal toxicity.

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* Expressed as water- and minor impurity-free test substance

Justification for classification or non-classification

In view of the discriminating single oral dose of 50 mg*/kg bw, at which all animals survived but transient clinical signs were evident, and the LD50 cut-off value considered to be 300 mg*/kg bw, the substance was classified as "harmful (Xn)" and "harmful if swallowed (R22) " according to EU-DSD classification rules [DIRECTIVE 67/548/EEC] and as "Category 3 (Danger, Toxic if swallowed)" according to EU-GHS classification rules [REGULATION (EC) 1272/2008]. In the acute dermal toxicity study, nine of ten animals survived the limit dose of 2000 mg*/kg. Therefore, according to EU classification rules, there is no labelling requirement regarding acute dermal toxicity.

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* Expressed as water- and minor impurity-free test substance