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Description of key information

Prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose oral toxicity was predicted for the test compound2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (6441-82-3 ). The study assumed the use of male and female Wistar rats in subchronic study of 8 months. No significant alterations were noted at the dose level of 515.59mg/Kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) for Dialkyl(C1-C14)dithiophosphoric acid, zinc salt is considered to be 515.59mg/Kg bw/day. Based on this value it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
515.59 mg/kg bw/day
Study duration:
chronic
Species:
rat
Quality of whole database:
K2 data from QSAR toolbox version 3.3

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Mode of Action Analysis / Human Relevance Framework

Additional information

Repeated dose oral toxicity:

Prediction model based estimation and data available for the target chemical was reviewed to determine the toxic nature of 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-

1,3,3-trimethyl-3H-indolium chloride (6441-82-3 )upon repeated exposure by oral, dermal and inhalation route of exposure. The studies are as mentioned below:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose oral toxicity was predicted for the test compound2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (6441-82-3 ). The study assumed the use of male and female Wistar rats in subchronic study of 8 months. No significant alterations were noted at the dose level of 515.59mg/Kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) for Dialkyl(C1-C14)dithiophosphoric acid, zinc salt is considered to be 515.59mg/Kg bw/day. Based on this value it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Another Repeated dose toxicity study for structurally and functionally similar read across chemical was performed by U.S. National Library of Medicine (HSDB (Hazardous Substances Data Bank, 2017) to determine the oral toxic nature1,2-dichloropropane (78-87-5) to determine its toxic nature. The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on mutation from the analogue substance. For this purpose subchronic study was conducted in male and female Fischer 344 rats by oral gavage for 13 weeks. The test substance was exposed to the animals at the dose concentration of0, 60, 125, 250, 500 or 1000 mg/kg bw/day by using corn oil as vehicle. The animals were observed for Mortality, clinical sign, Body weight, gross pathology and Histopathology.All male and female rats given 1000 mg/kg bw/day and 5/10 males from the 500 mg/kg bw group died before necropsy. All animals from the other treatment groups survived until study termination.No statistically significant effects were observed.All male and female rats given 1000 mg/kg bw/day and 5/10 males from the 500 mg/kg bw/day group died before necropsy. All animals from the other treatment groups survived until study termination. Significant effect were observed at the body weight and the histopatholgy of the liver at the dose group of 500 mg/kg/day of trated group compare to control. No significant effectwere observed at 250 mg/kg bw/day . Therefore NOAEL was considered to be 250 mg/kg bw/day for2 dichloropropane in male and female Fischer 344 rats by oral gavage for 13 weeks.Significant effects were observed at the body weight and the histopatholgy of the liver at the dose group of 500 mg/kg/day of trated group compare to control. No significant effectwere observed at 250 mg/kg bw/day . Therefore NOAEL was considered to be 250 mg/kg bw/day for2 dichloropropane in male and female Fischer 344 rats by oral gavage for 13 weeks.

Repeated inhalation study:

According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the substance 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (6441-82-3 ), which is reported as 3.31E-12 Pa at 25 deg C. Therefore this study is considered for waiver.

 

Repeated dermal study

The acute toxicity value for 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (6441-82-3 ) (as provided in section 7.2.3) is 4242 mg/kg bwmg/kg body weight. Also, given the use of the chemical; repeated exposure by the dermal route is unlikely since the use of gloves is common practice in industries. Thus, it is expected that 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (6441-82-3 ) shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (6441-82-3 )shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.

Based on the data available for the target chemical and its prediction, 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (6441-82-3 ) does not exhibit toxic nature upon repeated exposure by oral, inhalation and dermal route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Based on the data available for the target chemical and its read across, 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (6441-82-3 )does not exhibit toxic nature upon repeated exposure by oral, inhalation and dermal route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation