Reaction mass of 2- (palmitoylamino)ethyl acrylate and 2-(stearoylamino)ethyl acrylate

Endpoint summary

Description of key information

Summary

A toxicokinetic assessment was conducted in accordance with REACH Annex VIII 8.8.1. The substance Reaction mass of 2-(palmitoylamino)ethyl acrylate and 2-(stearoylamino)ethyl acrylate is a light yellow solid. It is an organic multi-constituent solid with a purity of 85-98% and a typical concentration of 92.4% (w/w). The impurities are Amides, C16-18, N-(hydroxyethyl) with a purity of 0-15% (w/w) and typical concentration of 5.6% (w/w) and Zirconium compounds with a purity of 0-2% (w/w) and typical concentration of 2% (w/w).

 

A full ADME toxicokinetic study in the rat is not available. In vivo studies covering the oral (acute oral toxicity study in rats, combined repeated dose oral toxicity study with reproduction/developmental toxicity screening test in rats) and dermal route (LLNA in mice) are available. There are no studies covering the inhalational route available. The toxicokinetic analysis is based on data from in vivo animal models and physicochemical data. Further details on endpoints are available in the IUCLID 6 registration dossier.

Based on the physicochemical data and available in vivo toxicological data, the substance is unlikely to be absorbed by oral, dermal or inhalation routes therefore distribution will be very low and it will be excreted unchanged in the faeces.

 

The absorption rates of 50% (oral), 50% (dermal) and 100% (inhalation) are accepted for chemical risk assessment purposes.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

50

Absorption rate - inhalation (%):

100

Additional information

Discussion

1. Physicochemical properties

In accordance with the ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7C Section R.7.12, the physicochemical properties can provide an insight into the potential behaviour of Reaction mass of 2-(palmitoylamino)ethyl acrylate and 2-(stearoylamino)ethyl acrylate in the body.

 

Absorption

Oral Absorption

The molecular weight (353-381 g/mol) is in the range for favourable oral absorption (<500 g/mol). The octanol/water partition coefficient (log Kow) of the substance (5.7-8.6 at 35°C) and poor solubility in water (0.7 mg/L, 20°C) indicates the substance is lipophilic. Oral absorption is expected to be low but if absorption does occur, it is likely via the lymphatic system through micellular solubilization.

 

Respiratory Absorption

The particle size distribution report for the substance indicates that 98.17% of particles are >2000μm. This indicates that the substance has no or low dustiness and exposure via the inhalation route is expected to be negligible.

 

Dermal Absorption

As the substance is poorly soluble in water, low dermal uptake is expected. The log Kow range indicates the substance is likely to remain in the stratum corneum with little systemic exposure. Overall dermal absorption is likely to be low.

 

Distribution/Metabolism/Excretion

The molecular weight, low water solubility and high log Kow do not favour wide distribution after any absorption. Based on the chemical structure, the substance may be excreted unchanged in the faeces.

 

2. Information from other studies in the dossier

 

Oral/GI absorption 

In an acute oral toxicity test in female Crl:WI Wistar rats (OECD 423/GLP) the LD50 was >2000 mg/kg bw.

 

In a combined repeated dose and reproduction/developmental toxicity screening test (OECD 422/GLP), the test item was administered to 4 groups of Crl:CD (SD) rats by gavage in 0.5% w/v methylcellulose solution at dose levels of 0 (7 males, 12 females), 110 (12 males/females), 330 (12 males/females), and 1000 mg/kg bw/day (7 males, 12 females), 7 days per week. Males were dosed from 14 days before mating until day before the necropsy throughout the mating period (42 days in total). Females were dosed from 14 days before mating until Day 13 of lactation (day of delivery was designated as Day 0 of lactation) throughout the mating and gestation periods and delivery. Non-copulated females were kept until day before the necropsy. Five males and 5 females (non-mating satellite females) each in the control and high dose groups were subjected to a recovery period for 14 days after the end of the dosing period. No treatment-related change was noted in any of the examinations in parental animals: clinical observation, functional observational battery, body weight measurement, food consumption measurement, urinalysis in males, haematology, blood chemistry, necropsy, organ weight measurement, histopathological examination, or male parental T4 hormone concentration measurement. In the parental animals, no treatment-related change was noted in any of the examinations: estrous cycle, copulation index, days until copulation, fertility index, gestation index, gestation length, numbers of implantations, delivery index, or parturition/maternal behaviour. In the offspring, no treatment-related change was noted in any of the examinations: sex ratio, birth index, stillborn index, viability index, external examination, body weight, anogenital distance, nipple development, necropsy, or plasma total T4 concentration. Based on the findings of this study the NOAEL (parental, offspring) of the test item for reproductive/developmental toxicity is 1000 mg/kg bw/day.

 

For chemical safety assessment purposes, based on the physicochemical properties and information in the dossier, an oral absorption rate of 50% is accepted.

 

Dermal absorption

In a dermal sensitization study in mice (OECD 429/GLP), the substance was not a skin sensitiser. Together with the physiochemical data, this data indicates that absorption via the dermal route is likely to be low.

 

The ECHA guidance criteria (Chapter R.7C) state that 10% dermal absorption is used when the molecular weight of the substance is >500 and the log Pow is <-1 or >4, otherwise 100% dermal absorption is used. In general, dermal absorption will not be higher than oral absorption, so for chemical safety assessment purposes a dermal absorption rate of 50% is accepted.”

 

Respiratory absorption-Inhalation

There are no studies via the inhalation route available.

 

For chemical safety assessment purposes, an inhalation absorption rate of 100% is accepted, using a conservative approach.

 

Distribution/Metabolism/Excretion

Based on the information provided from the physicochemical data and in vivo studies, the substance is unlikely to be absorbed by oral, dermal or inhalation routes therefore distribution will be very low and it will be excreted unchanged in the faeces.