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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics, other
Type of information:
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
Study period:
The assessment was conducted in April 2019
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Relevant studies were reviewed by a qualified toxicologist with a view to fulfilling the requ irements of Annex VIII (8.8).

Data source

Reference
Reference Type:
other:
Title:
Unnamed
Year:
2019

Materials and methods

Objective of study:
toxicokinetics
Test guideline
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.The assessment
is based on the Guidance on information requirements and chemical safety assessment R.7c:
Endpoint specific guidance (ECHA, November 2014)
GLP compliance:
no
Remarks:
Not relevant for assessment

Test material

Constituent 1
Chemical structure
Reference substance name:
5-bromo-5-nitro-1,3-dioxane
EC Number:
250-001-7
EC Name:
5-bromo-5-nitro-1,3-dioxane
Cas Number:
30007-47-7
Molecular formula:
C4H6BrNO4
IUPAC Name:
5-bromo-5-nitro-1,3-dioxane
Details on test material:
- Chemical name: 5-Brom-5-nitro- 1,3-dioxan
- Trade name: Bronidox
Specific details on test material used for the study:
Identification: 5-Bromo-5-nitro-1,3-dioxane
Batch (Lot) Number: 201807021
Expiry date: 30 Jun 2020 (expiry date) (taken from label)
Physical Description: White crystal powder
Storage Conditions: At room temperature
Radiolabelling:
no

Results and discussion

Metabolite characterisation studies

Metabolites identified:
not measured

Any other information on results incl. tables

TOXICOKINETIC BEHAVIOUR

The substance is a white colored powder with physico-chemical properties (Particle size: MMAD= 438µm; Vapor Pressure: 1.6 Pa at 20 ºC)

which imply the risk of

particle inhalation to be minimal. Furthermore, the supporting toxicological information suggests

any inadvertent inhalation is unlikely to lead to an elevation in systemic toxicity. The substance was identified to

be an ocular irritant with potential for severe damage in the BCOP assay; the in vitro genotoxicity panel indicates that

there are concerns for genotoxicity, with a psoitive result observed in the mouse lymphoma assay, subject to confirmatory in vivo testing.

The results from a dermal corrosivity study, in conjunction with the molecular weight (211 g/mol) and log

Pow (1.6) indicate significant absorption might occur via the dermis. Acute oral toxicity results showed the

LD50 to be ~500 mg/kg body weight, additionally the Oral (Gavage) Repeated Dose Toxicity Study in the

rat resulted in hepatic effects resulting in death at the highest dose, indicating gasto-intestinal absorption.

Absorption

The general physico-chemical properties of the substance : molecular weight (212.0 g/mol), water solubility (

4.77 g/L)

and partition coefficient (log Kow =1.6) indicate that significant absorption by the oral route can be expected..

Supporting results from the acute oral toxicity and Oral (Gavage) Repeated Dose Toxicity Study indicate absorption from the

gut.

Distribution

Information relating to the distribution of the substance is limited; however, the chemical

characteristics and findings from the Oral (Gavage) Repeated Dose Toxicity Study implies

systemic distribution would most likely occur via the serum following oral administration and gastric

absorption.

Metabolism

There is evidence of test item on metabolite influenced hepatic metabolism from the Oral (Gavage)

Repeated Dose Toxicity Study, with single cell necroses and slightly increased single-cell fatty degeneration in the liver,

Excretion

The most plausible route of clearance for low molecular weight, water soluble chemicals would be by renal excretion of substance or metabolites; there is evidence of substance mediated toxicity in the kidney, with congestion of the medullary-cortex border and protein casts in the nephrons.

Applicant's summary and conclusion

Conclusions:
The available information suggests that absorption of substance from the gastrointestinal tract following oral ingestion is highly likely based uponthe test items physico-chemical characteristics and relevent toxicity observed following oral dosing..
These characteristics together with the low volatility of the substance and particle size also indicate absorption via inhalation exposure of test item to be unlikely. Given the skin corrosivity of the substance and favorable physico-chemico properties, extensive dermal absorption can be expected. Any absorbed test material has the potential to undergo hepatic transformation and subsequent renal clearance.

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