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Link to relevant study record(s)

Reference
Endpoint:
basic toxicokinetics, other
Type of information:
other: expert statement
Adequacy of study:
key study
Study period:
April 19th, 2013
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Theoretical assessment 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:
absorption
Results:
For risk assessment purposes, 100% is used for oral, dermal and inhalation absorption

A substance can enter the body via the lungs, the gastrointestinal tract, and the skin. To determine the absorption rate, the different routes are assessed individually. For uptake from the gastro-intestinal tract after oral administration, a compound needs to be dissolved before it can be taken up. Accelerator (PT 25E or PT 25E/2) dissolves moderately well in water (21.8 g/l), therefore it will dissolve (at least in part) into the gastrointestinal fluids which will favor uptake via passive diffusion (passage through aqueous pores or carriage across membranes with the bulk passage of water). The molecular weight of Accelerator (PT 25E or PT 25E/2) is approximately 195.6, which is relatively small and the compound may therefore easily diffuse. Accelerator (PT 25E or PT 25E/2) is a multi-constituent compound, its main components have a log Pow between 2.0 and 2.5. This moderate log P will also favor passive diffusion, since it enables crossing of lipid biomembranes.

 

For risk assessment purposes oral absorption of Accelerator (PT 25E or PT 25E/2) is set at 100%, based on its water solubility, its low molecular weight and its moderate log Pow. The oral toxicity data do not provide reason to deviate from the proposed oral absorption factor.

 

Once absorbed, wide distribution of the test substance throughout the body is expected based on its water solubility and low molecular weight. Absorbed Accelerator (PT 25E or PT 25E/2) is most likely excreted via urine or via bile. Based on its moderate partition coefficient (2 -2.5), it is unlikely that Accelerator (PT 25E or PT 25E/2) will accumulate in adipose tissue based on repeated intermittent exposure pattern. Due to its water solubility, the substance is expected to be gradually eliminated when exposure stops. Based on this, the bioaccumulative potential of Accelerator (PT 25E or PT 25E/2) is expected to be low.

 

The low vapour pressure (1.4 × 10-3Pa) indicates that Accelerator (PT 25E or PT 25E/2) is not volatile and that it is not likely that the substance will reach the nasopharyncheal region or subsequently the tracheo/bronchial/pulmonary region via inhalation of a vapour. Accelerator (PT 25E or PT 25E/2) is a liquid, therefore information on the particle size distribution is not applicable

If Accelerator (PT 25E or PT 25E/2) reaches the tracheobronchial region, it is likely to dissolve within the mucus lining the respiratory tract and to get absorbed due to its water solubility and low molecular weight. Furthermore, due to its irritating properties it may damage the epithelium lining the respiratory tract, which will further promote systemic uptake of the substance.

Based on the above data, for risk assessment purposes the inhalation absorption of Accelerator (PT 25E or PT 25E/2) is set at 100%.

 

Accelerator (PT 25E or PT 25E/2) is a viscous liquid. The first layer of the skin, the stratum corneum, is a barrier for hydrophilic compounds. Since Accelerator (PT 25E or PT 25E/2) has a log Pow between 2 and 2.5, the lipophilicity of the substance is optimal for dermal absorption: it will easily cross the stratum corneum. More importantly, Accelerator (PT 25E or PT 25E/2) is shown to be a skin irritant, so exposure of the skin will lead to damage of the skin integrity, leading to enhanced penetration. After the skin surface is damaged, Accelerator (PT 25E or PT 25E/2) will be absorbed easily due to its low molecular weight and moderate water solubility.

Based on the above data, for risk assessment purposes the dermal absorption of Accelerator (PT 25E or PT 25E/2) is set at 100%. The results of the toxicity studies do not provide reasons to deviate from this proposed dermal absorption factor.

 

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.

Description of key information

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.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
100
Absorption rate - inhalation (%):
100

Additional information

A substance can enter the body via the lungs, the gastrointestinal tract, and the skin. To determine the absorption rate, the different routes are assessed individually. For uptake from the gastro-intestinal tract after oral administration, a compound needs to be dissolved before it can be taken up. Accelerator (PT 25E or PT 25E/2) dissolves moderately well in water (21.8 g/l), therefore it will dissolve (at least in part) into the gastrointestinal fluids which will favor uptake via passive diffusion (passage through aqueous pores or carriage across membranes with the bulk passage of water). The molecular weight of Accelerator (PT 25E or PT 25E/2) is approximately 195.6 g/mol, which is relatively small and the compound may therefore easily diffuse. Accelerator (PT 25E or PT 25E/2) is a multi-constituent compound, its main components have a log Pow between 2.0 and 2.5. This moderate log P will also favor passive diffusion, since it enables crossing of lipid biomembranes.

 

For risk assessment purposes oral absorption of Accelerator (PT 25E or PT 25E/2) is set at 100%, based on its water solubility, its low molecular weight and its moderate log Pow. The oral toxicity data do not provide reason to deviate from the proposed oral absorption factor.

 

Once absorbed, wide distribution of the test substance throughout the body is expected based on its water solubility and low molecular weight. Absorbed Accelerator (PT 25E or PT 25E/2) is most likely excreted via urine or via bile. Based on its moderate partition coefficient (2 -2.5), it is unlikely that Accelerator (PT 25E or PT 25E/2) will accumulate in adipose tissue based on repeated intermittent exposure pattern. Due to its water solubility, the substance is expected to be gradually eliminated when exposure stops. Based on this, the bioaccumulative potential of Accelerator (PT 25E or PT 25E/2) is expected to be low.

 

The low vapour pressure (1.4 × 10-3Pa) indicates that Accelerator (PT 25E or PT 25E/2) is not volatile and that it is not likely that the substance will reach the nasopharyncheal region or subsequently the tracheo/bronchial/pulmonary region via inhalation of a vapour. Accelerator (PT 25E or PT 25E/2) is a liquid, therefore information on the particle size distribution is not applicable. If Accelerator (PT 25E or PT 25E/2) reaches the tracheobronchial region, it is likely to dissolve within the mucus lining the respiratory tract and to get absorbed due to its water solubility and low molecular weight. Furthermore, due to its irritating properties it may damage the epithelium lining the respiratory tract, which will further promote systemic uptake of the substance.

Based on the above data, for risk assessment purposes the inhalation absorption of Accelerator (PT 25E or PT 25E/2) is set at 100%.

 

Accelerator (PT 25E or PT 25E/2) is a viscous liquid. The first layer of the skin, the stratum corneum, is a barrier for hydrophilic compounds. Since Accelerator (PT 25E or PT 25E/2) has a log Pow between 2 and 2.5, the lipophilicity of the substance is optimal for dermal absorption: it will easily cross the stratum corneum. More importantly, Accelerator (PT 25E or PT 25E/2) is shown to be a skin irritant, so exposure of the skin will lead to damage of the skin integrity, leading to enhanced penetration. After the skin surface is damaged, Accelerator (PT 25E or PT 25E/2) will be absorbed easily due to its low molecular weight and moderate water solubility.

Based on the above data, for risk assessment purposes the dermal absorption of Accelerator (PT 25E or PT 25E/2) is set at 100%. The results of the toxicity studies do not provide reasons to deviate from this proposed dermal absorption factor.