Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics, other
Type of information:
other: Assessment based on available information
Adequacy of study:
supporting study
Reliability:
other: Assessment of available experimental data

Data source

Materials and methods

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
- Identification: 1,3-Bis (4-hydroxy benzoyl) benzene
- Appearance: Off white crystalline powder
- Test item storage: At room temperature
- Stable under storage conditions until: 01 April 2021 (expiry date)
- Batch # MMHBB-002/18

Results and discussion

Metabolite characterisation studies

Metabolites identified:
not measured

Any other information on results incl. tables

Toxicokinetic qualitative assessment

There are no standard toxicokinetics studies available in the dataset. The following assessment relies on available toxicological studies and physico-chemical properties (REACH guidance R.7.12, V 3.0, 2017).

 

ABSORPTION

 

Oral /GI absorption

 

The molecular weight of 13BHBB below 500 is favourable for oral absorption.

 

The substance has a limited water solubility therefore it is not expected to readily dissolve into the gastrointestinal fluids. However, the LogKow of 2.4 combined with low water solubility may still allow passive diffusion and/or micellar solubilisation. Thus, some absorption can occur.

No toxicity was observed in the acute oral toxicity study at up to 2000 mg/kg. In the repeated dose toxicity study, some effects were noted at the highest dose (limit dose of 1000 mg/kg/day) which provide evidence that the substance can be absorbed to some extent by the oral route. Based on the few effects observed, the absorption may be limited.

 

In conclusion, 13BHBB can be absorbed to some extent by the oral route. Only a few systemic effects were present at the limit dose and no sufficient data are available for estimating the absorption rate.

In the absence of further information on the quantity absorbed, the default maximised absorption is set at 100% for the oral and dermal routes.

 

  

Respiratory tract absorption

 

The substance is a crystalline powder with a very low vapour pressure at 20°C, therefore inhalation of vapours is not considered relevant. The particle size distribution indicates that the majority of the particles have a diameter above 200 µm. Potential exposure to dusts of diameters below 100 µm may occur. However, considering the low water solubility, most of the dust that could be inspired are likely to deposit in the upper respiratory tract and will be cleared out or swallowed before sufficient dissolution into the mucus can occur for absorption.

 

There were no particles below 10 µm and less than 10% below 44 µm, which limits the potential to reach the deeper lung regions. Based on the low water solubility and LogKow, absorption could still occur viamicellar solubilisation.

 

In the absence of further information on the fraction absorbed by inhalation, the default absorption is set at 100% for the inhalation route.

 

 

Dermal absorption

 

The relatively low molecular weight of 318 can allow some dermal absorption, although the bulkiness due to the benzene cycles can slow down the migration into the skin.

The Log Kow value of 2.4 allows absorption of the substance into the stratum corneum, however, the water solubility below 1 mg/l could limit its further transfer into the epidermis and systemic circulation.

 

In addition,13BHBB caused no skin irritation in the in vitro skin irritation tests, and no effects in the skin sensitization test following repeated topical applications. Therefore, no enhanced absorption is expected in relation to potential skin damages.

 

In the absence of further information, the default absorption is set at 100% for the dermal route.

 

 

DISTRIBUTION

 

No sufficient data are available for estimating distribution rate and tissues affinity.

In the combined repeated dose toxicity study and reproduction/developmental toxicity screening test there were limited effects on organs. However, the retinal atrophy noted in 2 females of the high dose group, may be an evidence of systemic distribution.

 

 

METABOLISM

 

No sufficient data are available to predict the metabolic changes and formation of potential metabolites. The positive result observed in the in vitro gene mutation assay in the presence of metabolic activation may suggest the substance could undergo metabolic transformation.

 

 

EXCRETION

 

Characteristics favourable to urinary excretion are low molecular weight (below 300 in the rat), high water solubility, and ionisation of the molecule at the pH of urine.

Excretion of 13BHBB as such in urine does not appear likely considering its physico-chemical properties,but it could occur after undergoing metabolisation.

Applicant's summary and conclusion

Conclusions:
There are no experimental toxicokinetic study available for 1,3-Bis (4-hydroxy benzoyl) benzene (13BHBB). The toxicokinetic behaviour of 1,3-Bis (4-hydroxy benzoyl) benzene (13BHBB) was estimated based on the available dataset.
Based on the available studies, including physico-chemical properties and repeated dose toxicity study, there are some evidence that the substance can be absorbed to some extent by the oral route and distributed further into the body. Absorption by the dermal and respiratory routes is not excluded but could be limited. No sufficient data are available for predicting the metabolisation and excretion pattern.