2,2-dimethylpropane-1,3-diyl dibenzoate

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics

Remarks:

Toxicokinetic assumption

Type of information:

other: Toxicokinetic assumption

Adequacy of study:

other information

Study period:

Assumption based on data which are compiled in the IUCLID data base

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The statement is based on toxicological data and not on a toxicokinetic study.

Objective of study:

other: information/assumption on toxicokinetics based on toxicological data

Qualifier:

no guideline followed

Principles of method if other than guideline:

There are no experimental toxicokinetic data with 2,2-dimethylpropane-1,3-diyldibenzoate available. The following remarks on toxicokinetics of 2,2-dimethylpropane-1,3-diyldibenzoate are therefore based on the available studies which were compiled in the respective IUCLID database.
These assumptions follow the procedure indicated in chapter R.7c of the ECHA “Guidance on information requirements and chemical safety assessment” (version 3.0, November 2017).

GLP compliance:

no

Specific details on test material used for the study:

2,2-Dimethylpropane-1,3-diyl dibenzoate is a white to yellowish solid with mild odor. Its molecular weight is 312 g/mol. Its melting point is about 46.5°C at 1017 hPa and the boiling point is >300°C at 1004 hPa. 2,2-Dimethylpropane-1,3-diyl dibenzoate is not inhalable, because it is a wax with a low vapor pressure estimated to be < 0.0001 hPa at 25°C. The water solubility is 1.16 mg/l at 20 °C. The octanol-water partition coefficient (log Kow) of 2,2-dimethylpropane-1,3-diyl dibenzoate was determined to be 4.7 at 25°C and pH 7.

Radiolabelling:

no

Species:

other: information/assumption on toxicokinetics based on toxicological data

Strain:

other: information/assumption on toxicokinetics based on toxicological data

Details on test animals or test system and environmental conditions:

information/assumption on toxicokinetics based on toxicological data

Route of administration:

other: information/assumption on toxicokinetics based on toxicological data

Vehicle:

other: information/assumption on toxicokinetics based on toxicological data

Details on exposure:

information/assumption on toxicokinetics based on toxicological data

Duration and frequency of treatment / exposure:

information/assumption on toxicokinetics based on toxicological data

Remarks:

Doses / Concentrations:
information/assumption on toxicokinetics based on toxicological data

Details on study design:

information/assumption on toxicokinetics based on toxicological data

Type:

other: toxicokinetics

Results:

Specific investigations are not available. The available statements refer to physico-chemial and toxicological data.

Type:

absorption

Results:

Absorption via oral, dermal or inhalation route is anticipated to be low.

Type:

distribution

Results:

The available studies on acute and repeated dose toxicity do not provide information on distribution

Type:

metabolism

Results:

No data available. From results of the in vitro genotoxicity tests it can be assumed that DNA reactive metabolites will most propabely not be generated in mammals in the course of hepatic biotransformation.

Type:

excretion

Results:

No data available. In general the major routes of excretion of an organic compound from the systemic circulation are the urine and/or feces.

Metabolites identified:

no

Executive summary:

Specific investigations are not available. The available statements refer to physico-chemical and toxicological data. Absorption via oral, dermal or inhalation route is anticipated to be low. The available acute and repeated dose toxicity studies do not provide information on distribution. No metabolites are identified. From results of the in vitro genotoxicity tests it can be assumed that DNA reactive metabolites will most probably not be generated in the course of hepatic transformation. There is no information on excretion. In general the major routes of excretion of an organic compound from systemic circulation are the urine and / or faeces.

Description of key information

Specific investigations are not available. The available statements refer to physico-chemical and toxicological data. Absorption via oral, dermal or inhalation route is anticipated to be low. The available acute and repeated dose toxicity studies do not provide information on distribution. No metabolites are identified. From results of the in vitro genotoxicity tests it can be assumed that DNA reactive metabolites will most probably not be generated in the course of hepatic transformation. There is no information on excretion. In general the major routes of excretion of an organic compound from systemic circulation are the urine and / or faeces.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Additional information

Introduction

There are no experimental toxicokinetic data with 2,2-dimethylpropane-1,3-diyl dibenzoate available. The following remarks on toxicokinetics of 2,2-dimethylpropane-1,3-diyl dibenzoate are therefore based on the available studies which were compiled in the respective IUCLID database.

These assumptions follow the procedure indicated in chapter R.7c of the ECHA “Guidance on information requirements and chemical safety assessment” (version 3.0, November 2017).

 

 

Available physico-chemical information taken into account

2,2-Dimethylpropane-1,3-diyl dibenzoate is a white to yellowish solid with mild odor. Its molecular weight is 312 g/mol. Its melting point is about 46.5°C at 1017 hPa and the boiling point is >300°C at 1004 hPa. 2,2-Dimethylpropane-1,3-diyl dibenzoate is not inhalable, because it is a wax with a low vapor pressure, which is estimated to be < 0.0001 hPa at 25°C. The water solubility is 1.16 mg/l at 20 °C. The octanol-water partition coefficient (log Kow) of 2,2-dimethylpropane-1,3-diyl dibenzoate was determined to be 4.7 at 25°C and pH 7.

 

From these data it can be concluded that exposure via vapor is an unlikely route of exposure.

 

 

Absorption

The physico-chemical characteristics of 2,2-dimethylpropane-1,3-diyl dibenzoate (molecular weight of 312 g/mol, water solubility of 1.16 mg/l and log Kow of 4.7) indicate high lipophilicity. Therefore some substance uptake by micellular solubilisation might be considered. However, in an acute oral study 5000 mg/kg bw 2,2-dimethylpropane-1,3-diyl dibenzoate was applied to rats as suspension in corn oil with unknown particle size (Wilson 1978). Animals revealed only unspecific findings and no animal died; LD50 > 2000 mg/kg bw. Furthermore in a repeated dose oral gavage study in rats according to OECD TG 407 over a period of 28 days the resulting NOAEL accounts for 1000 mg/kg bw/day (limit dose), because the test substance was well tolerated without relevant clinical signs and mortality. Gross and histopathological examinations did not reveal relevant alterations (van Otterdijk 2015).

 

Referring to dermal absorption the low water solubility of 1.16 mg/l and the log Kow of 4.7 for 2,2-dimethylpropane-1,3-diyl dibenzoate and the molecular weight >100 indicate that the rate of transfer between the stratum corneum and epidermis is limited and therefore also dermal absorption into the body. The acute dermal toxicity study in rabbits (20000 mg/kg bw. 24 h) yielded no mortality, no clinical signs and animals gained weight during the post application period (Wilson 1978). In acute skin and eye irritation studies in rabbits no systemic intolerance reactions have been reported (Wilson 1978) and no sensitizing effect has been identified in the Local Lymph Node assay (Vohr 2014). These observations are in line with the assumptions by physico-chemical data.

 

Absorption by inhalation exposure can be assumed to be limited based on the molecular weight of 2,2-dimethylpropane-1,4-diyl dibenzoate of 312 g/mol, the log Kow of 4.7 (cited from IUCLID), and water solubility 1.16 mg/l (cited from IUCLID). In a respective inhalation study rats were exposed to saturated vapor and displayed only unspecific reactions to the vapor exposure at the start of the exposure but no animal died and gross pathological examination showed no organ-alterations (Leong 1978).

 

 

Distribution/Accumulation

There is no specific investigation available on distribution of 2,2-dimethylpropane-1,3-diyl dibenzoate. Based on the low water solubility (1.16 mg/l) and the high log Kow (above 4) it is likely the substance to distribute into cells and the intracellular concentration may be higher than extracellular concentration. However, in the repeated dose oral study over a period of 28 days rats received doses up to and including 1000 mg/kg bw/day (van Otterdijk 2015). There were no test item related alterations in organ weights and the histopathological findings were of low incidence and not considered to be test item related. Thus this study provides no information on distribution of the substance.

Based on the low water solubility and the high log Kow accumulation cannot be excluded. From the results of the subacute oral rat study there is no reason to assume that either the unchanged substance or its metabolites may accumulate in fatty tissues.

 

 

Metabolism

There is no specific information available. Based on the results of the in vitro genotoxicity tests with 2,2-dimethylpropane-1,3-diyl dibenzoate [Ames test (Nern 2014), HPRT (Wollny 2014), and MNT in vitro (Nern 2014)] it is concluded that DNA reactive metabolites of 2,2-dimethylpropane-1,3-diyl dibenzoate will most probably not to be generated in mammals in the course of hepatic biotransformation.

 

 

Excretion

There is no specific information available. In general the major routes of excretion of an organic compound from the systemic circulation are the urine and/ or faeces.