4-hydroxybenzophenone

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Remarks:

This theoretical assessment was prepared, taking all currently available relevant information into account, based on the REACH Guidance: Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7c Endpoint specific guidance.

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Qualifier:

no guideline required

Guideline:

other: This theoretical assessment was prepared, taking all currently available relevant information into account, based on the REACH Guidance: Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7c Endpoint specific guidance.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-hydroxybenzophenone

EC Number:

214-507-1

EC Name:

4-hydroxybenzophenone

Cas Number:

1137-42-4

Molecular formula:

C13H10O2

IUPAC Name:

4-benzoylphenol

Test material form:

solid: particulate/powder

Details on test material:

Identification: 4-hydroxy-benzophenone
Molecular formula: C13H10O2
Molecular weight: 198.22
CAS Number: 1137-42-4
Description: White crystal
Purity: 99.72 %

Results and discussion

Preliminary studies:

Acute oral toxicity (rat)
Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening (oral, rat)
Skin corrosion (in vitro)
Skin irritation test (in vitro)
Eye irritation test (in vitro, BCOP)
Eye irritation test (in vitro, Epiocular)
Sensitisation (in chemico, DPRA)
Sensitisation (in vitro, KeratinoSens)
Sensitization (WoE)
Sensitization (in vivo, LLNA)
Ames test
Chromosome aberration test

Toxicokinetic / pharmacokinetic studies

Details on absorption:

After exposure, a substance can enter the body via the gastrointestinal tract, the lungs, and the skin. Since different parameters are relevant for absorption via the different routes of exposure, the uptake via these three routes will be addressed individually.

After oral administration, a solid compound needs to be dissolved before it can be taken up from the gastrointestinal tract. The moderate water solubility of 4-hydroxy-benzophenone (0.126 g/L at 20 °C), will favour absorption to some extent, and the substance is expected to dissolve into the gastrointestinal fluids. Consequently, the substance is expected to be available for uptake. The molecular weight of the test substance (198.22) will favour the uptake, and absorption via passive diffusion (passage of small water-soluble molecules through aqueous pores or carriage across membranes with the bulk passage of water) may occur. Its moderate partition coefficient (log Pow between 1.6 and 2.2) is favourable for absorption via passive diffusion. The chemical structure shows that the test substance has potentially ionisable groups. It is not clear if the test substance would be ionized at pH values usually found in the gastrointestinal tract (roughly between 2 and 8). Ionization of the substance can hamper uptake. In conclusion, for risk assessment purposes oral absorption of 4-hydroxy-benzophenone is set at 100%, taking into account its moderate water solubility which will favour absorption, but also considering potential uptake via passive diffusion. The oral toxicity data does not provide indications to deviate from this value.

4-hydroxy-benzophenone has been found to have a low vapor pressure (≤ 2.2 x 10-5 Pa at 20 °C), which indicates that its availability for inhalation as a vapor is low. On the other hand, 4-hydroxy-benzophenone is a powder with a mass median aerodynamic diameter (MMAD) of 83.7 µm. In humans, particles with aerodynamic diameters below 100 μm have the potential to be inhaled. Particles with aerodynamic diameters below 50 μm may reach the thoracic region and those below 15 μm the alveolar region of the respiratory tract. As for 4-hydroxy-benzophenone 50% of the particles have an aerodynamic diameter lower than 64 µm a considerable part of the particles have the potential to reach the tracheobronchial region. 10% of the particles have an aerodynamic diameter lower than 13.2 µm, and may reach the alveolar region. Due to the moderate water solubility, 4-hydroxy-benzophenone may dissolve in the mucus lining the respiratory tract, and its small molecular size will favour absorption via passive diffusion. Bigger particles may settle in the nasopharyngeal region and through the action of clearance mechanism may be transported out of the respiratory tract and swallowed. The moderate log Pow will favour absorption. The test substance is not surface active, and tests on its irritant/corrosive properties are inconclusive. Therefore, it is not clear if damage of the epithelia may be expected that may enhance uptake. Taking these considerations together it is concluded that for risk assessment purposes, the inhalation absorption of 4-hydroxy-benzophenone is set at 100%.

As 4-hydroxy-benzophenone is a solid, dry substances have to dissolve into the surface moisture of the skin before uptake can occur. The moderate partition coefficient (log Pow between 1.6 and 2.2) allows uptake in the stratum corneum, and its moderate water solubility (0.126 g/L at 20 °C) will favour the partitioning from the stratum corneum into the epidermis. Moreover, the test substance is not surface active but tests on its irritant/corrosive properties are inconclusive. Therefore, it is not clear if damage of the epithelium may be expected that may enhance uptake. According to the criteria given in the REACH Guidance, 10% dermal absorption will be considered in case MW >500 and log Pow <-1 or >4, otherwise 100% dermal absorption should be used. Thus according to the guideline, for risk assessment purposes dermal absorption of 4-hydroxy-benzophenone is set at 100%.

Details on distribution in tissues:

Based on its moderate partition coefficient (log Pow = 1.6 to 2.2), it is unlikely that 4-hydroxy-benzophenone might accumulate in adipose tissue, therefore the bioaccumulation potential of 4-hydroxy-benzophenone is expected to be low.

Details on excretion:

Once absorbed, distribution of the substance throughout the body is expected due to its low molecular weight, and its moderate water solubility will favour distribution. 4-hydroxy-benzophenone may be metabolized in the gastrointestinal tract or the liver and be excreted through bile.

Any other information on results incl. tables

Parameter	Value	Project
Acute oral toxicity (rat)	LD50   > 2000 mg/kg bw	CRL 20151992
Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening (oral, rat)	Parental NOAEL: at least 300 mg/kg bw/day	CRL 20151994
	Reproduction NOAEL: at least 300 mg/kg bw/day
	Developmental NOAEL: at least 300 mg/kg bw/day
Skin corrosion (in vitro)	Not corrosive	CRL 20151983
Skin irritation test (in vitro)	Inconclusive	CRL 20151984
Eye irritation test (in vitro,BCOP)	Inconclusive	CRL 20151985
Eye irritation test (in vitro,Epiocular)	Inconclusive	CRL 20151986
Sensitisation (in chemico,DPRA)
Sensitisation (in vitro,KeratinoSens)	Negative	CRL 20151989
Sensitization (WoE)
Sensitization (in vivo, LLNA)	Positive	CRL 20151990
	Inconclusive	CRL 20151988
	Not sensitizer	CRL 20202009
Ames test	Not mutagenic (with and without S9)	CRL 20151997
Chromosome aberration test	Clastogenic (with S9)	CRL 20151998

Applicant's summary and conclusion

Conclusions:

A toxicokinetic assessment was performed based on the available data of the substance. 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) for risk assessment purposes. The bioaccumulation potential is expected to be low.