Reaction mass of C12-14 tert-alkylamines and dimethyl hydrogen phosphate and methyl dihydrogen phosphate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Type of information:

other: Assessment based upon available information.

Adequacy of study:

key study

Study period:

May 2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Information selected for the toxicokinetic assessment is primarily study data. Studies were conducted inaccordance with recognised testing guidelines.

Data source

Reference

Reference Type:

other: Assessment

Title:

Unnamed

Year:

2018

Results and discussion

Any other information on results incl. tables

The test material, is a substance of Unknown or Variable composition, Complex reaction products or Biological materials (UVCB) with multiple constituents. The physical state of the substanceis a liquid and therefore, potential inhalation of the substance is negligible.

 

The water solubility and partition coefficientof the substance could not be determined due to micelle formation in aqueous test solution and the critical micelle concentration was determined to be 363 mg/Lat 20 °C and pH 7. Quantitative structure–activity relationship (QSAR) analysis has showed that the test material are bioavailable via the oral route in accordance with Lipinski Rule Oasis. In addition, the oral LD₅₀was estimated to be in the range of 300 – 2000 mg/kg body weight with hunched posture observed in acute oral toxicity study in female rats. In a 14-day repeated dose oral range-finding toxicity study in rats, the substance was not well tolerated at dosage levels of 500 and 1000 mg/kg/day as evidenced by moribundity, mortality, body weight losses, reduced food consumption, and/or adverse clinical observations. All rats in the 1000 mg/kg/day group were found dead or euthanized in extremis following 1 – 2 doses of the substance. In the combined repeated dose oral toxicity study with the reproductive/developmental toxicity screening test in rats,lower mean body weights, body weight gains, and food consumption were noted in adult rats receiving 250 mg/kg/day, the highest dosage level tested, but no substance-related effects were observed on reproductive performance up to the highest dosage level tested. No information is currently available on possible degradation products produced in the gastrointestinal tract.

 

The substance is expected to be absorbed via the dermal route and the local lymph node assay (LLNA) in mouse showed an EC₃of 4.2%.

 

Additionally, the ready biodegradability test of the substance showed that it was not readily biodegradable. The 72-hour ErC₅₀to freshwater green alga, 48-hour EC₅₀toDaphnia magnaand 96-hour LC₅₀to rainbow trout of the substance were determined to be 1.9, 6.8, and 18 mg/L, respectively, in the acute toxicity tests to aquatic organisms. The QSAR analysis has showed moderate potential for bioaccumulation in aquatic organisms.

 

In conclusion, based upon the available data,the substance is expected to be bioavailable but the systemic toxicity is low.

Applicant's summary and conclusion

Conclusions:

In conclusion, based upon the available data,the substance is expected to be bioavailable but the systemic toxicity is low.