Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate

Endpoint summary

Description of key information

There is no specific investigation on toxicokinetics, metabolism and distribution available.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

There are no experimental toxicokinetic data available for 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' and this statement is based on available data as physico-chemical data and toxicological data like skin irritation/corrosion, eye irritation, skin sensitization, in vitro mutagenicity and acute and repeated dose oral toxicity studies. This assumption follows the procedure indicated in the "Guidance on information requirements and chemical safety assessment chapter R.7c" of the ECHA guidance document (Version 3.0, June 2017).

 

Available physico-chemical information taken into account:

 

Physical state:

'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' is an organic liquid with a relative density of 0.998 at 20°C.

 

Structure:

'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' is a "multi constituent substance", consisting of

49.1 % benzyl 2-ethylhexyl adipate (CAS No. 58394-64-2),

28.0 % bis(2-ethylhexyl) adipate (CAS No. 103-23-1) and

21.9 % dibenzyl adipate (CAS No. 2451-84-5).

 

Molecular weight:

The molecular weight of benzyl 2-ethylhexyl adipate (CAS No. 58394-64-2) is 348.49 g/mol.

The molecular weight of bis(2-ethylhexyl) adipate (CAS No. 103-23-1) is 370.58 g/mol.

The molecular weight of dibenzyl adipate (CAS No. 2451-84-5) is 326.40 g/mol.

 

Water solubility:

The water solubility at 20 °C is 0.844 mg/L.

 

Partition coefficient:

The partition coefficient (log Kow) is > 4.5 at 24°C and pH 6.4.

 

Surface tension:

Based on the structure, surface activity is not anticipated.

 

Vapor pressure:

QSAR determination of the vapor pressure at 25°C of each constituent of 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' gave a calculated vapor pressure of 0.00105

 

Estimation of oral absorption:

Some oral absorption by micellular solubilisation might be considered, based on the physico-chemical data: low water solubility (below 1 mg/L) and high log Kow (above 4).

A subacute oral gavage study in rats was performed according to OECD guideline 407 and indicated some absorption. Increased incidence and severity of renal hyaline droplets in corticotubular cells in males, considered to represent α2-microglobulin were observed starting at 100 mg/kg bw/day. Although these effects are considered to be male rat specific and not relevant for humans, these data indicate the compound is absorbed after oral dosing.

 

Overall:

Oral absorption is assumed based on physico-chemical properties and oral toxicity experiments.

 

Estimation of dermal absorption:

Dermal absorption is likely to be low based on water solubility below 1 mg/L, high log Kow (above 4), and no surface activity.

 

Dermal toxicity data does not indicate relevant dermal absorption:

Skin irritation: Not irritating and no systemic effects

Skin sensitization: Negative in LLNA

Dermal toxicity data: No data available

 

Overall:

Dermal absorption is likely to be low.

 

Estimation of absorption via inhalation:

Respiratory absorption is anticipated to be low based on vapor pressure below 0.5 kPa, low water solubility (below 1 mg/L) and high log Kow (above 4).

An acute inhalation toxicity test according to OECD TG 403 was conducted to determine the potential of 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' to produce toxicity from a 4 hour exposure via inhalation (nose-only exposure) route. The tested air concentration was 5080 mg/m³. The mass median aerodynamic diameter was estimated to be 1.72 µm. All animals survived the exposure to the test atmosphere. Following exposure all animals exhibited irregular respiration. However, the animals recovered from this symptom by day 3 and appeared active and healthy for the remainder of the 14 day observation period. Although all animals lost body weight by day 1, all animals showed a continued weight gain thereafter through day 14. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14 day observation period.

 

Overall:

Some absorption by inhalation might be assumed based on the acute toxicity study data but vapor pressure is low.

 

Overall estimation on absorption:

Some absorption is anticipated by the oral and inhalation route and similar absorption values were taken for these routes in the DNEL calculations. Dermal absorption is considered to be low compared to oral and inhalation absorption and a factor of 2 was applied in the DNEL calculation to take the low dermal absorption into account.

 

Estimation of distribution:

Based on the low water solubility (below 1 mg/L) and high log Kow (above 4) the compound might distribute into cells. In a subacute oral gavage study in rats according to OECD guideline 407 increased incidence and severity of renal hyaline droplets in corticotubular cells in males, considered to represent α2-microglobulin were observed starting at 100 mg/kg bw/day. Although these effects are considered to be male rat specific and not relevant for humans, these data indicate the compound is absorbed after oral dosing and kidneys are a target organ in rodents.

 

Estimation of accumulation:

Accumulation of the compound in tissues cannot be excluded based on the physicochemical parameters: low water solubility (below 1 mg/L) and high log Kow (above 4).

Taking into account all available toxicological data no accumulation was observed for the compound in oral studies ranging from 4 weeks up to 1 year. Although the study design and reporting of the chronic study by Bornmann shows limitations compared to actual guidelines these results are in agreement with a recent fully valid subacute guideline study. There are no findings which are relevant for the human situation up to and including 1000 mg/kg bw/day.

 

Overall:

Taking into account all available data including chronic toxicity data, no accumulation is anticipated.

 

Estimation of metabolism:

In vitro genotoxicity data do not indicate any genotoxic metabolites. The substance is negative in the absence and in the presence of S9 extracts (Ames test, gene mutation assay in mammalian cells (HPRT), and in vitro micronucleus test).

 

Estimation of excretion:

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