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Reference
Endpoint:
basic toxicokinetics in vivo
Type of information:
other: expert statement
Adequacy of study:
weight of evidence
Study period:
2019-05-24
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: An assessment of the toxicokinetic behaviour of hydroxyacetone was performed, taking into account the available physico-chemical and toxicological data.
Objective of study:
absorption
distribution
excretion
Guideline:
other: ECHA Guidance R.7c
Principles of method if other than guideline:
An assessment of the toxicokinetic behaviour of hydroxyacetone was performed, taking into account the available physico-chemical and toxicological data.
GLP compliance:
no
Type:
absorption
Results:
The absorption rate of hydroxyacetone is assumed to be 100 % via the oral, dermal and inhalation route.
Type:
distribution
Results:
The substance is expected to be distributed widely through the body via blood circulation.
Type:
excretion
Results:
The low molecular weight (74 g/mol) and high water solubility of hydroxyacetone favours urinary excretion.
Details on absorption:
Oral absorption
An acute oral toxicity study according to OECD Guideline 423 (Class method, GLP) was conducted with hydroxyacetone. No treatment-related symptoms were observed and no pathological changes were found that indicate a toxic effect of the test item. Due to the absence of toxic effects, this study does not provide information regarding the oral absorption potential of the test item. However, based on the physical-chemical properties it is likely that a considerable amount of hydroxyacetone is absorbed when applied orally. In fact, absorption by passive diffusion is favoured for substances with moderate log P values (between -1 and 4). With a log P of 0.3, hydroxyacetone is likely to follow this route of absorption. Additionally, based on the low molecular weight (< 200 g/mol) and due to the high solubility in water (> 100 kg/L), hydroxyacetone may also be absorbed by passing through aqueous pores or being carried through the epithelial barrier by the bulk passage of water.
Taken together, based on the physical-chemical properties an oral absorption rate of 100 % is assumed for hydroxyacetone. It is assumed that the absence of toxic effects in the acute oral toxicity study according to OECD Guideline 423 is rather caused by the lack of acute toxic properties of hydroxyacetone than by deficient absorption.

Dermal absorption
In a study according to OECD Guideline 439 (RhE, GLP) hydroxyacetone was shown to have no skin irritating effects. Therefore, the substance is not expected to destroy the barrier function of the skin. Nevertheless, considering the physical-chemical properties, dermal absorption of hydroxyacetone may be possible. Absorption in the stratum corneum is favoured for substances with a molecular weight below 100 g/mol. To cross the lipid-rich stratum corneum a certain degree of lipophilicity is required (Log P > 0). Hydroxyacetone has a molecular weight of 74 g/mol and a log P of 0.3. Thus, hydroxyacetone might be able to be absorbed by the stratum corneum. To partition from the stratum corneum into the viable part of the epidermis, a substance must be sufficiently soluble in water (>1 mg/L). Although the very high water solubility of > 100 kg/L may limit the amount of the substance which is readily available for dermal uptake, substance penetration to the deeper of the viable layers of the epidermis cannot be fully ruled.
Overall, based on the physical-chemical properties of hydroxyacetone dermal absorption may be limited but cannot be fully excluded. For precautionary reasons a dermal absorption rate of 100 % is assumed.

Respiratory absorption
As the substance is a liquid, no inhalable particles occur. Due to the vapour pressure of 901 Pa at 25°C and a boiling point of 136°C, hydroxyacetone has a moderate volatility. Thus, it may be available for inhalation as a vapour. Vapours of very hydrophilic substances as hydroxyacetone are retained within the mucus preventing them from penetrating into the lower respiratory tract. Thus, absorption through the huge gas exchange region of the lung is unlikely to occur. Rather, hydrocyacetone is transported out of the deposition region with the mucus and swallowed. Certain amounts may also be absorbed by passing through aqueous membrane pores.
Based on the available data, it can be concluded that inhalatory exposure is possible. As worst-case, 100 % inhalation absorption is assumed.
Details on distribution in tissues:
Due to the low molecular weight (74 g/mol) and high water solubility (> 100 kg/L), hydroxyacetone is expected to be widely distributed in the body via blood circulation. It may diffuse through the aqueous pores of cell membranes. Based on the low log P (< 3) no accumulation in fatty tissue or stratum corneum is expected.
Details on excretion:
The low molecular weight (74 g/mol) and high water solubility of hydroxyacetone favours urinary excretion.
Conclusions:
For precautionary reasons, the absorption rate of hydroxyacetone is assumed to be 100 % via the oral, dermal and inhalation route. The substance is expected to be distributed widely through the body via blood circulation. No accumulation is expected. The main excretion route is urinary excretion.
Executive summary:

The toxicokinetic profile of hydroxyacetone (CAS 116-09-6) was assessed based on the substance’s physical-chemical properties in combination with existing of toxicity data. For precautionary reasons, the absorption rate of hydroxyacetone is assumed to be 100 % via the oral, dermal and inhalation route. The substance is expected to be distributed widely through the body via blood circulation. No accumulation is expected. The main excretion route is urinary excretion.

Description of key information

The toxicokinetic profile of hydroxyacetone (CAS 116-09-6) was assessed based on the substance’s physical-chemical properties in combination with existing of toxicity data. For precautionary reasons, the absorption rate of hydroxyacetone is assumed to be 100 % via the oral, dermal and inhalation route. The substance is expected to be distributed widely through the body via blood circulation. No accumulation is expected. The main excretion route is urinary excretion.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
100
Absorption rate - inhalation (%):
100

Additional information

Toxicokinetic Statement for Hydroxyacetone (CAS 116-09-6)

General

The toxicokinetic profile of hydroxyacetone (CAS 116-09-6) was assessed based on the substance’s physical-chemical properties in combination with existing of toxicity data.

Substance identity

Table 1: Physical-chemical properties of hydroxyacetone

 

 

Hydroxyacetone (CAS 116-09-6)

Structural formula

C3H6O2

Structure

Molecular Weight [g/mol]

74

Physical state

Liquid

Water Solubility (20°C)

> 100 kg/L

Log P

0.3

Vapour Pressure (25°C)

901 Pa

 

 

Oral absorption

An acute oral toxicity study according to OECD Guideline 423 (Class method, GLP) was conducted with hydroxyacetone. No treatment-related symptoms were observed and no pathological changes were found that indicate a toxic effect of the test item. Due to the absence of toxic effects, this study does not provide information regarding the oral absorption potential of the test item. However, based on the physical-chemical properties it is likely that a considerable amount of hydroxyacetone is absorbed when applied orally. In fact, absorption by passive diffusion is favoured for substances with moderate log P values (between -1 and 4). With a log P of 0.3, hydroxyacetone is likely to follow this route of absorption. Additionally, based on the low molecular weight (< 200 g/mol) and due to the high solubility in water (> 100 kg/L), hydroxyacetone may also be absorbed by passing through aqueous pores or being carried through the epithelial barrier by the bulk passage of water.

Taken together, based on the physical-chemical properties an oral absorption rate of 100 % is assumed for hydroxyacetone. It is assumed that the absence of toxic effects in the acute oral toxicity study according to OECD Guideline 423 is rather caused by the lack of acute toxic properties of hydroxyacetone than by deficient absorption.

 

Dermal absorption

In a study according to OECD Guideline 439 (RhE, GLP) hydroxyacetone was shown to have no skin irritating effects. Therefore, the substance is not expected to destroy the barrier function of the skin. Nevertheless, considering the physical-chemical properties, dermal absorption of hydroxyacetone may be possible. Absorption in the stratum corneum is favoured for substances with a molecular weight below 100 g/mol. To cross the lipid-rich stratum corneum a certain degree of lipophilicity is required (Log P > 0). Hydroxyacetone has a molecular weight of 74 g/mol and a log P of 0.3. Thus, hydroxyacetone might be able to be absorbed by the stratum corneum. To partition from the stratum corneum into the viable part of the epidermis, a substance must be sufficiently soluble in water (>1 mg/L). Although the very high water solubility of > 100 kg/L maylimit the amount of the substance which is readily available for dermal uptake, substancepenetration to the deeper of the viable layers of the epidermis cannot be fully ruled.

Overall, based on the physical-chemical properties of hydroxyacetone dermal absorption may be limited but cannot be fully excluded. For precautionary reasons a dermal absorption rate of 100 % is assumed.

Respiratory absorption

As the substance is a liquid, no inhalable particles occur. Due to the vapour pressure of 901 Pa at 25°C and a boiling point of 136°C, hydroxyacetone has a moderate volatility. Thus, it may be available for inhalation as a vapour. Vapours of very hydrophilic substances as hydroxyacetone are retained within the mucus preventing them from penetrating into the lower respiratory tract. Thus, absorption through the huge gas exchange region of the lung is unlikely to occur. Rather, hydrocyacetone is transported out of the deposition region with the mucus and swallowed. Certain amounts may also be absorbed by passing through aqueous membrane pores.

Based on the available data, it can be concluded that inhalatory exposure is possible. As worst-case, 100 % inhalation absorption is assumed.

 

Distribution and Accumulation

Due to the low molecular weight (74 g/mol) and high water solubility (> 100 kg/L), hydroxyacetone is expected to be widely distributed in the body via blood circulation. It may diffuse through the aqueous pores of cell membranes. Based on the low log P (< 3) no accumulation in fatty tissue or stratum corneum is expected.

 

Elimination

The low molecular weight (74 g/mol) and high water solubility of hydroxyacetone favours urinary excretion.

Summary

For precautionary reasons, the absorption rate of hydroxyacetone is assumed to be 100 % via the oral, dermal and inhalation route. The substance is expected to be distributed widely through the body via blood circulation. No accumulation is expected. The main excretion route is urinary excretion.

References

ECHA (2017): Guidance on Information Requirements and Chemical Safety Assessment; Chapter R.7c: Endpoint specific guidance, version 3, ISBN 978-92-9495-838-9