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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Link to relevant study record(s)

Reference
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.

The physical state of the substance is a liquid and therefore, potential inhalation of the substance is negligible.

 

The water solubility and partition coefficient (Log Pow)of the substance are 0.233mg/L and > 6.2, respectively.  The typical molecular mass of the substance (C18H35O6PS2) is 442.57 Daltons.  These data indicate that the substance has low water solubility (< 0.1 mg/L) and is a highly lipophilic (Log Pow > 5.6) molecule, and thus the substance is not bioavailable via the oral route in accordance with Lipinski's rule of five.  In addition, the oral LD50was > 2500 mg/kg body weight with hunched posture, diuresis, diarrhea, and dehydration observed at 2000 mg/kg, the highest doses tested 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 250, 500, and 1000 mg/kg/day as evidenced by moribundity, mortality, and/or adverse clinical observations. All rats in the 1000 mg/kg/day group were found dead or euthanized in extremis following 1 – 3 doses of the substance. In the combined repeated dose oral toxicity study with the reproductive/developmental toxicity screening test in rats, the substance was not well tolerated at dosage levels of 150 mg/kg/day in females as evidenced by moribundity, mortality, and/or adverse clinical observations, but no test substance-related effects on clinical pathology including T4, histopathology, functional observational battery (FOB), and reproductive and developmental assessments were noted. The purity of the substance used in the two repeated dose oral toxicity studies (14-day oral toxicity study and combined repeated dose oral toxicity study with the reproductive/developmental toxicity screening test) was ≥ 82% and the certificate of analysis showed the test substance contained approximately 15% dibutyl fumarate(CASRN 105-75-9). Quantitative structure–activity relationship (QSAR) analysis has showed that the substance itself is not reactive to DNA and proteins while dibutyl fumarate has high protein binding potency. The moribundity, mortality, and adverse clinical observations might therefore be due to the major impurity, dibutyl fumarate, under the conditions of the studies. No information is currently available on possible degradation products produced in the gastrointestinal tract.

 

The low water solubility and high lipophilicity of the substance also indicate that it is not expected to be absorbed via the dermal route.  Although thelocal lymph node assay (LLNA) in mouse showed an EC3of 9.5% that was likely due to the major impurity of the test substance,dibutyl fumarate,a known sensitizer, under the conditions of the test. The QSAR analysis showed that the substance had no protein binding alerts. Therefore, the substance itself was not considered to be a skin sensitizer.

 

Additionally, the ready biodegradability test of the substance showed that it was 42.6% biodegradation after 28 days and was not considered readily biodegradable. The measured test concentrations of the substance in aquatic medium were very low (< 0.039 mg/L), less than its water solubility (0.233mg/L) in the acute toxicity tests in aquatic organisms (algae, daphnia, and fish). The substance is therefore expected to have low potential for bioaccumulation in aquatic organisms although the substance is persistent and its Log Pow exceeds 5.

In conclusion, based upon the available data, bioavailability of the substance is expected to be very limited and the substance has low potential toinducesystemic toxicity.

Conclusions:
In conclusion, based upon the available data, bioavailability of the substance is expected to be very limited and the substance has low potential toinducesystemic toxicity.

Description of key information

In conclusion, based upon the available data, bioavailability of the substance is expected to be very limited and the substance has low potential to induce systemic toxicity.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential

Additional information