Chloroacetaldehyde

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: summary

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: EPA summary

Data source

Reference

Reference Type:

publication

Title:

HEALTH AND ENVIRONMENTAL EFFECTS PROFILE FOR CHLOROACETALDEHYDE

Author:

U.S. ENVIRONMENTAL PROTECTION AGENCY; CINCINNATI, OH 45268

Year:

1986

Bibliographic source:

EPA/600/X-86/151

Materials and methods

Test guideline

Qualifier:

no guideline followed

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Chloroacetaldehyde

EC Number:

203-472-8

EC Name:

Chloroacetaldehyde

Cas Number:

107-20-0

Molecular formula:

C2H3ClO

IUPAC Name:

2-chloroacetaldehyde

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other: no bioaccumulation expected due to high reactivity of CAA
Pertinent data regarding the absorption, distribution or excretion of chloroacetaldehyde could not be located in the available literature.
Chloroacetaldehyde is a major metabolite of a number of chlorinated compounds (U.S. EPA, 1980a). After oral administration to rats,
chloroacetaldehyde is first conjugated with glutathione and subsequently metabolized along two pathways (Green and Hathllay. 1977).
Urinary metabolites include N-acetyl(2-hydroxyethyl) cysteine, S-(carboxymethyl) cysteine and thiodiglycollic acid.

Executive summary:

Chloroacetaldehyde is a metabolite of a variety of halogenated organics (U.S. EPA. 1980a), which have received considerable study (Guengerich et a1. 1980; Gwinner et a1.1983). The only metabolism study in which chloroacetaldehyde itself was administered to experimental animals was done by Green and Hathway (1977). Four adult Alderly-Park male rats were administered a 50 mg/kg aqueous solutlon of chloroacetaldehyde by gavage. An unspecified number of control animals was also used. Collected urine was divided for analysis into acetic acid and HCl fractions. The former fraction was analyzed by GC-mass spectometry and mass fragmentography for N-acetyl-S-( 2-hydroxyethyl) cysteine, and the HCl fraction was analyzed by GC-mass spectometry for thiodiglycollic and chloroacetic acids.

The results allowed Green and Hathway (1977) to propose a scheme for the metabolism of chloroacetaldehyde (the scheme is a portion of a more detailed metabolic pathway for vinyl chloride metabolism). Mass fragmentography revealed the presence of N-acetyl-S(2-hydroxyethyl) cysteine and S-(carboxymethyl) cysteine, but not chloroacetic acid, In the urine of separate group of rats led to a thiodiglycollic yield of only 0.5%. Green and Hathway (1977) therefore deduced that S-(carboxymethyl) cysteine was metabolized by a route independent of N-acetyl-S-(2-hydroxyethyl) cysteine, after chloroacetaldehyde administration.

Chloroacetaldehyde is conjugated to glutathione, to yield S-formylmethylglutathione. Further degradation and glutathionase activation results in the appearance of N-acetyl-S-(2-hydroxyethyl) cysteine. Alternatively, S-formyl-methylglutathione can be dehydrogenated and acted upon by liver and kidney glutathionases to yield S-(carboxymethyl) cysteine. Transamination followed by oxidative decarboxylation then leads to the major urinary metabolite, thiodiglycollic acid. The three urinary metabolites observed after oral chloroacetaldehyde administration in rats were thiodiglycollic acid, S-(carboxymethyl) cysteine and N-acetyl-S-(2-hydroxyethyl) cysteine (Green and Hathway, 1977). No other information regarding other routes of elimination was located in the available literature.