2-methylenepropane-1,3-diyl diacetate

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics, other

Remarks:

assessment of toxicokinetic behavior

Type of information:

other: other: In accordance with REACH Annex VIII (8.8) an assessment of toxicokinetic behavior has been conducted to the extent that can be derived from the relevant available information

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: other: Relevant studies were reviewed with a view to fulfilling the requirements of Annex VIII (8.8)

Objective of study:

toxicokinetics

Qualifier:

no guideline followed

Principles of method if other than guideline:

In accordance with REACH Annex VIII (8.8) an assessment of toxicokinetic behaviour has been conducted to the extent that can be derived from the relevant available information.

GLP compliance:

no

Remarks:

Not relevant for assessment

Conclusions:

The toxicokinetic properties of MPDAc are evaluated based on its physicochemical and toxicological properties provide by the sponsor, the results of QSAR modeling and read-across.
The LogPow, water solubility and the molecular weight of MPDAc indicate the possibility of oral exposure. The possibility of oral exposure for the tested substance is also supported by 28-day oral toxicity study and the combined repeated dose toxicity study with the reproduction/developmental toxicity screening. The analysis of structure and analogue suggest the chemical of stability in acid and high hydrolysis speed in base. After oral exposure, the tested substance in the stomach might be absorbed in the form of prototype. While in intestinal tract, MPDAc might be absorbed as the intact and hydrolytes. The physico-chemical characters, the QSAR prediction and toxicity test indicate possibility of dermal exposure. And MPDAc might have no potential for static inhalation exposure.
The LogPow, water solubility and theoretical apparent distribution volume indicate main distribution in blood and no possibility of high fat distribution for MPDAc. There might be tissue distribution of heart, lung, liver, spleen, kidney, thymus and adrenal gland for the tested substance indicated by the acute oral toxicity test and the combined repeated dose toxicity study with the reproduction/developmental toxicity screening. The QSAR prediction for MPDAc suggest no possibility of high plasma protein binding.
OECD QSAR Toolbox predict the pathways of rat in vivo, skin and microorganism metabolism for MPDAc, which mainly include hydrolysis and oxidation. Compared with MPDAc, being of good solubility itself, the water solubility of metabolites and kidney excretion will be increased significantly. Therefore, it is considered that MPDAc, its hydrolysates and metabolites would be mainly excreted in urine.
MPDAc might has no high reactivity with biomacromolecules, and the LogPow predicts no adipose enrichment and high tissue affinity. MPDAc, its hydrolysates and metabolites are experimentally or theoretically proved as good water solubility. The QSAR prediction for MPDAc suggest no possibility of high plasma protein binding. In the recovery group of combined repeated dose toxicity study with the reproduction/developmental toxicity screening, among the changes noted at the end of the dosing period, reversibility or recovery trend was noted. It is believed that there might be no bioaccumulation of MPDAc with these evidences.

Description of key information

The toxicokinetic properties of MPDAc are evaluated based on its physicochemical and toxicological properties provide by the sponsor, the results of QSAR modeling and read-across.
The LogPow, water solubility and the molecular weight of MPDAc indicate the possibility of oral exposure. The possibility of oral exposure for the tested substance is also supported by 28-day oral toxicity study and the combined repeated dose toxicity study with the reproduction/developmental toxicity screening. The analysis of structure and analogue suggest the chemical of stability in acid and high hydrolysis speed in base. After oral exposure, the tested substance in the stomach might be absorbed in the form of prototype. While in intestinal tract, MPDAc might be absorbed as the intact and hydrolytes. The physico-chemical characters, the QSAR prediction and toxicity test indicate possibility of dermal exposure. And MPDAc might have no potential for static inhalation exposure.
The LogPow, water solubility and theoretical apparent distribution volume indicate main distribution in blood and no possibility of high fat distribution for MPDAc. There might be tissue distribution of heart, lung, liver, spleen, kidney, thymus and adrenal gland for the tested substance indicated by the acute oral toxicity test and the combined repeated dose toxicity study with the reproduction/developmental toxicity screening. The QSAR prediction for MPDAc suggest no possibility of high plasma protein binding.
OECD QSAR Toolbox predict the pathways of rat in vivo, skin and microorganism metabolism for MPDAc, which mainly include hydrolysis and oxidation. Compared with MPDAc, being of good solubility itself, the water solubility of metabolites and kidney excretion will be increased significantly. Therefore, it is considered that MPDAc, its hydrolysates and metabolites would be mainly excreted in urine.
MPDAc might has no high reactivity with biomacromolecules, and the LogPow predicts no adipose enrichment and high tissue affinity. MPDAc, its hydrolysates and metabolites are experimentally or theoretically proved as good water solubility. The QSAR prediction for MPDAc suggest no possibility of high plasma protein binding. In the recovery group of combined repeated dose toxicity study with the reproduction/developmental toxicity screening, among the changes noted at the end of the dosing period, reversibility or recovery trend was noted. It is believed that there might be no bioaccumulation of MPDAc with these evidences.