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Link to relevant study record(s)

Reference
Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data from IARC and IPCS Monograph
Objective of study:
absorption
distribution
excretion
metabolism
Qualifier:
according to
Guideline:
other: as mentionoed below
Principles of method if other than guideline:
The absorption, distribution, metabolism and excretion of the chemical chloral hydrate has been determined.
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material: 2,2,2-Trichloroethane-1,1-diol (Chloral hydrate)
- Molecular formula: C2-H3-Cl3-O2
- Molecular weight: 165.4026g/mol
- Smiles notation: C(C(O)O)(Cl)(Cl)Cl
- InChl: RNFNDJAIBTYOQL-UHFFFAOYSA-N
- Substance type: Organic
- Physical state: Solid
Radiolabelling:
not specified
Species:
other: Humans
Sex:
not specified
Route of administration:
oral: drinking water
Vehicle:
water
Details on exposure:
Details not available
Duration and frequency of treatment / exposure:
Details not available
Remarks:
Doses / Concentrations:
15 mg/kg bw
No. of animals per sex per dose:
Details not available
Control animals:
no
Type:
absorption
Results:
After oral administration, chloral hydrate is rapidly absorbed from the gastrointestinal tract. Its biotransformation to trichloroethanol must be rapid, since no parent compound could be detected in even the first samples taken 10 min after administration
Type:
distribution
Results:
Peak levels of trichloroethanol and trichloroethanol glucuronide were reached within 20 to 60 min after oral administration of aqueous solution.
Type:
metabolism
Results:
Chloral hydrate is rapidly metabolized in both hepatic and extrahepatic tissues to trichloroethanol and trichloroacetic acid.
Type:
excretion
Results:
The major route of excretion of the metabolites of chloral hydrate is the urine. (Source EPA)
Metabolites identified:
yes
Details on metabolites:
trichloroethanol
trichloroacetic acid and
trichloroethanol glucuronide
Conclusions:
Since chloral hydrate is rapidly metabolized after oral absorption to produce metabolites that are excreted predominantly in urine, it can be expected that chloral hydrate shall have low bio-accumulation potential.
Executive summary:

The absorption, distribution, metabolism and excretion of the chemical chloral hydrate has been determined. From the information available chloral hydrate is shown to be rapidly metabolized after oral absorption to produce trichloroethanol, trichloroacetic acid and trichloroethanol glucuronide metabolites that are excreted predominantly in urine, thus it can be expected that chloral hydrate shall have low bio-accumulation potential.

Description of key information

Since chloral hydrate is rapidly metabolized after oral absorption to produce metabolites that are excreted predominantly in urine, it can be expected that chloral hydrate shall have low bio-accumulation potential.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential

Additional information

Different experimental studies on basic toxicokinetics in humans have been reviewed for the substance Chloral hydarate and has been summarised below as weight of evidence approach:

Data obtained from IARC Monograph 1995, indicates that the chloral hydrate is shown to be rapidly metabolized after oral absorption to produce trichloroethanol, trichloroacetic acid and trichloroethanol glucuronide metabolites that are excreted predominantly in urine, thus it can be expected that chloral hydrate shall have low bio-accumulation potential.

Similary in the data obtained from abstract of peer reviewed journal, The bioavailability and pharmacokinetics of chloral hydrate have been studied in human volunteers Eighteen healthy male subjects (aged 20–31 years) were given 250 or 500 mg chloral hydrate either in immediate-release or enteric-coated modified-release capsules or as a solution. Because of the extensive firstpass metabolism of chloral hydrate, the bioavailability of trichloroethanol was used as a surrogate for its absorption. The bioavailability of chloral hydrate given in capsules amounted to 94.8–101.6% of that given as a solution. The terminal half-lives for the elimination of trichloroethanol and trichloroacetic acid from plasma were 9.3–10.2 and 89–94 h, respectively. Chloral hydrate itself could be detected only 8 to 60 min after application at very low concentrations in some of the plasma samples. Thus, due to the extremely short terminal half-life of chloral hydrate i.e. 8-60 min, it is expected to have low bio-accumulation potential.

Thus based on the above data and by applying weight of evidence approach it can be concluded that chloral hydrate shall have low bio-accumulation potential as it is rapidly metabolised and excreted.