[(9-oxo-9H-thioxanthen-2-yl)oxy]acetic acid

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:

January 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Objective of study:

toxicokinetics

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:

[(9-oxo-9H-thioxanthen-2-yl)oxy]acetic acid

EC Number:

282-803-8

EC Name:

[(9-oxo-9H-thioxanthen-2-yl)oxy]acetic acid

Cas Number:

84434-05-9

Molecular formula:

C15H10O4S

IUPAC Name:

2-[(9-oxo-9H-thioxanthen-2-yl)oxy]acetic acid

Test material form:

solid

Specific details on test material used for the study:

Identification: CMTX 2-carboxymethyloxy-thioxanthone
Molecular formula: C15H10O4S
Molecular weight: 286.3
CAS Number: 84434-05-9
Description: Yellow powder
Purity: 98.25 %

Results and discussion

Preliminary studies:

Acute oral toxicity (rat)
Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening (oral, rat)
Skin corrosion/irritation tests (in vitro)
Eye irritation test (in vitro, EpiOcular)
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 substance needs to be dissolved before it can be taken up from the gastrointestinal tract. The water solubility of CMTX 2-carboxymethyloxy-thioxanthone is relatively low (0.0186 g/L at 20 °C), therefore the substance is expected to dissolve into the gastrointestinal fluids only to a limited extent. Consequently, the substance is expected to be poorly available for uptake. The molecular weight of the test substance (286.6) will favor 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, but this may be limited due to its relatively low water solubility. Its moderate partition coefficient (log Pow between 1.7 and 2.6) is also favorable 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 CMTX 2-carboxymethyloxy-thioxanthone is set at 50%, taking into account its relatively low water solubility which will limit absorption, but also considering potential uptake via passive diffusion. The oral toxicity data does not provide indications to deviate from this value.

CMTX 2-carboxymethyloxy-thioxanthone is a powder. It has been found to have a low vapor pressure (< 1.3 x 10-8 Pa at 20°C), which indicates that its availability for inhalation as a vapor is low. CMTX 2-carboxymethyloxy-thioxanthone is a powder with a mass median aerodynamic diameter (MMAD) of 8.8 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. It has been found that 90% of the particles of CMTX 2-carboxymethyloxy-thioxanthone have an aerodynamic diameter lower than 16.6 µm which implies that those particles can reach the tracheobronchial and alveolar regions. Due to the relatively low water solubility, CMTX 2-carboxymethyloxy-thioxanthone may dissolve in the mucus lining of the respiratory tract to a limited extent, hampering absorption. However, particles might be taken up by phagocytosis and transported to the blood via lymphatic system or engulfed by alveolar macrophages and translocated to the pulmonary interstitium and lymphoid tissues. The moderate log Pow will favor absorption. The test substance is not surface active and has no skin irritant/corrosive properties found in in vitro tests. Taking these considerations together it is concluded that for risk assessment purposes, the inhalation absorption of CMTX 2-carboxymethyloxy-thioxanthone is set at 100%.

As CMTX 2-carboxymethyloxy-thioxanthone is a solid, dry particles have to dissolve into the surface moisture of the skin before uptake can occur. The moderate partition coefficient (log Pow between 1.7 and 2.6) allows uptake in the stratum corneum, but its relatively low water solubility (0.0186 g/L at 20 °C) will limit the partitioning from the stratum corneum into the epidermis. Its molecular weight is 286.6. According to the criteria given in the REACH Guidance2, 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, CMTX 2-carboxymethyloxy-thioxanthone uptake is set at 100%. However, it is in general assumed that dermal absorption does not exceed oral absorption. Moreover, as discussed above, the substance is not surface active, thus damage on the respiratory epithelia that could enhance the uptake is not expected. Therefore, for risk assessment purposes, dermal absorption is set at 50%.

Details on distribution in tissues:

Once absorbed, distribution of the substance throughout the body is expected due to its moderate molecular weight.

Details on excretion:

The relatively low water solubility may hamper distribution. CMTX 2-carboxymethyloxy-thioxanthone may be metabolized in the gastrointestinal tract or the liver and be excreted through bile. Based on its moderate coefficient (log Pow = 1.7 to 2.6), it is unlikely that CMTX 2-carboxymethyloxy-thioxanthone might accumulate in adipose tissue, therefore the bioaccumulation potential of CMTX 2-carboxymethyloxy-thioxanthone is expected to be low.

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 50% (oral), 100% (inhalation) and 50% (dermal) for risk assessment purposes. The bioaccumulation potential is expected to be low.

Executive summary:

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 50% (oral), 100% (inhalation) and 50% (dermal) for risk assessment purposes. The bioaccumulation potential is expected to be low.