N-bromosuccinimide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Remarks:

assessment report based on all relevant phys/chem and toxicological information

Type of information:

other: assessment report based on all relevant phys/chem and toxicological information

Adequacy of study:

key study

Study period:

2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Materials and methods

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

Assessment report based on all available relevant information.

GLP compliance:

no

Applicant's summary and conclusion

Conclusions:

A toxicokinetic assessment was performed based on the available data of N-Bromosuccinimide. Based on the physical/chemical properties of the substance, absorption factors for this substance are derived to be 100% (oral), 100% (inhalation) and 100% (dermal).

Executive summary:

A toxicant can enter the body via the gastrointestinal tract, the lungs and the skin. In general, a compound needs to be dissolved before it can be taken up from the gastrointestinal tract after oral administration. N-Bromosuccinimide has a moderate water solubility of 14.8 g/L at 20°C. This implies that the substance will readily dissolve into the gastrointestinal fluids and uptake via passive diffusion (passage of small water-soluble molecules through aqueous pores or carriage across membranes with the bulk passage of water) will take place. The moderate molecular weight (approx. 178) will not hamper this process. N-Bromosuccinimide has a low to moderate partition coefficient (log Pow= -1.19), therefore this substance will dissolve to a limited extent in lipids and has the ability to cross epithelia by passive diffusion. No data are available on the dissociation constant of N-Bromosuccinimide, therefore it is unclear in which state (ionized or not ionized) the substance will be present under physiological circumstances in the stomach or intestinal tracts. Since it is generally thought that ionized substances do not readily diffuse across biological membranes, the state of the substance might hamper uptake. Considering all this data, there are no indications that oral absorption of N-Bromosuccinimide is largely hampered: its water solubility, its moderate molecular size, and its ability to dissolve in lipids will favour systemic uptake. Therefore, for risk assessment purposes oral absorption of N-Bromosuccinimide of 100% can be considered. The oral toxicity data do not provide reason to deviate from the proposed oral absorption factor. Local effects were observed in the oral repeated dose toxicity study, which also are indicative for high uptake due to disruption of the integrity of the biological membranes.

The medium vapour pressure (1.9 × 10-3Pa at 20°C) indicate that N-Bromosuccinimide is a substance with medium volatility. Therefore it cannot be excluded that N-Bromosuccinimide will reach the nasopharyncheal region or subsequently the tracheo/bronchial/pulmonary region via inhalation of vapour. N-Bromosuccinimide is a powder, with a mean particle size of around 137 µm; 56.8% of the particles have a particle size below 100μm, 15.8% below 50μm and 2.09% of the particles are smaller than 15μm. In humans, particles with aerodynamic diameters below 100μm have the potential to be inhaled. Particles with aerodynamic diameters below 50μm may reach the thoracic region and those below 15μm can reach the alveolar region of the respiratory tract. Based on the size of the particles, 15.8% below 50μm is therefore expected to be able to reach all parts of the lung upon inhalation. If the substance reaches these regions, N-Bromosuccinimide is likely to dissolve in the mucus lining the respiratory tract and to get absorbed. Since N-Bromosuccinimide is able to both dissolve in water and in lipids (to some extent), uptake through respiratory epithelium will take place. Therefore it is concluded that for risk assessment purposes the inhalation absorption of N-Bromosuccinimide should be set at 100%. 

N-Bromosuccinimide is a powder and as its water solubility is moderate, it will be able to dissolve into the surface moisture of the skin to allow uptake and partition from the stratum corneum into the epidermis. Its moderate ability to dissolve in lipids will favour crossing of epidermal barriers. Its moderate molecular size is not expected to hamper uptake through dermal epithelium. According to the guidance on dermal absorption, a default value of 100% skin absorption is generally used unless molecular weight is above 500 and log Pow is outside the range [-1, 4]. Since the substance has a molecular weight of approx. 178 and a log Powof -1.19, it does not meet either criteria. Moreover, N-Bromosuccinimide is classified as skin irritating and eye corrosive, which will facilitate absorption, and is sensitizing, indicating that it can penetrate the skin. Local effects due to skin irritating properties are also indicative for high dermal uptake, due to disruption of the integrity of the biological membranes. Therefore, the dermal absorption of N-Bromosuccinimide is considered to be 100% for risk assessment purposes.

 

Once absorbed, distribution of the test substance throughout the body is expected based on its water solubility and moderate molecular weight. After uptake, N-Bromosuccinimide is broken down to bromide and succinate. Excess bromide is excreted via urine, whereas succinate is a physiological metabolite and part of the TCA (KREBS) cycle. Based on its partition coefficient, N-Bromosuccinimide is not expected to significantly accumulate in adipose tissue, which is further indicated by its water solubility and moderate molecular size.Therefore bioaccumulation is expected to be limited.