Hydrocarbons, C10, aromatics, >1% naphthalene

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

N/A

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: The documentation is from secondary literature.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

basic toxicokinetics

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

N/A

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: The documentation is from secondary literature.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across source

Metabolites identified:

yes

Details on metabolites:

Nine urinary metabolites, namely, N-acetyl-S-[2-(4-ethenylphenyl)-2-hydroxyethyl]-L-cysteine, N-acetyl-S-[1-(4-ethenylphenyl)-2-hydroxyethyl]-L-cysteine, N-acetyl-S-[1-(4-formylphenyl)-2-hydroxyethyl]-L-cysteine, 1-(4-ethenylphenyl)ethane-1,2-diol, 4-ethenylbenzoic acid, 4-ethenylbenzoyl-glycine, 1-ethenyl-4-(1-hydroxyethyl)benzene, 4-(1,2-dihydroxyethyl)benzoic acid, (4-carboxymethylphenyl)acetylglycine, N-acetyl-S-[2-carboxy-1-(4-ethenylphenyl)ethyl]-L-cysteine, and two isomeric beta-D-glucosiduronates derived from 1-(4-ethenylphenyl)ethane-1,2-diol

Conclusions:

Interpretation of results: low bioaccumulation potential based on study results

Executive summary:

This data is being read across from the source study that tested 1,4-diethenylbenzene based on analogue read across.

Biotransformation of 1,4-diethenylbenzene in rat was studied. Nine urinary metabolites, namely, N-acetyl-S-[2-(4-ethenylphenyl)-2-hydroxyethyl]-L-cysteine, N-acetyl-S-[1-(4-ethenylphenyl)-2-hydroxyethyl]-L-cysteine, N-acetyl-S-[1-(4-formylphenyl)-2-hydroxyethyl]-L-cysteine, 1-(4-ethenylphenyl)ethane-1,2-diol, 4-ethenylbenzoic acid, 4-ethenylbenzoyl-glycine, 1-ethenyl-4-(1-hydroxyethyl)benzene, 4-(1,2-dihydroxyethyl)benzoic acid, (4-carboxymethylphenyl)acetylglycine, N-acetyl-S-[2-carboxy-1-(4-ethenylphenyl)ethyl]-L-cysteine, and two isomeric beta-D-glucosiduronates derived from 1-(4-ethenylphenyl)ethane-1,2-diol, were isolated and identified by n.m.r. and mass spectrometry.  GC-mass spectral analysis of the methylated urine extract allowed the identification of four other metabolites, as 4-ethenylphenylacetic acid, 4-ethenylphenylacetylglycine, 4-ethenylmandelic acid, and 4-ethenylphenylglyoxylic acid. The structures of the identified metabolites indicate that the main reactive intermediate in the metabolism of 1,4-diethenylbenzene is 4-ethenylphenyloxirane. The first step in the biotransformation of 1,4-diethenylbenzene is the formation of an oxirane. Subsequent steps lead to oxidation of the second ethenyl group leading to the aldehyde N-acetyl-S-[1-(4-formylphenyl)-2-hydroxyethyl]-L-cysteine metabolite. Rats dosed with a single i.p. dose excreted nearly 5.6% of the dose as the glycine conjugate 12, irrespective of the dose. In contrast, the total thioether fraction decreased significantly with increasing dose, being 23 +/- 3, 17 +/- 5 and 12 +/- 1% of dose at 100, 200 and 300 mg/kg, respectively (mean +/- SD).

Data source

Reference

Reference Type:

publication

Title:

Biotransformation of diethenylbenzenes. I. Identification of the main urinary metabolites of 1,4-diethenylbenzene in the rat.

Author:

Lindhart, I.

Year:

1989

Bibliographic source:

Xenobiotica. Jun;19(6):645-53. 1989

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 417 (Toxicokinetics)

Principles of method if other than guideline:

Biotransformation of 1,4-diethenylbenzene in rat was studied.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

1,4-divinylbenzene

EC Number:

203-266-8

EC Name:

1,4-divinylbenzene

Cas Number:

105-06-6

Molecular formula:

C10H10

IUPAC Name:

1,4-divinylbenzene

Constituent 2

Reference substance name:

1,4-diethenylbenzene

IUPAC Name:

1,4-diethenylbenzene

Radiolabelling:

not specified

Test animals

Species:

rat

Strain:

not specified

Sex:

not specified

Administration / exposure

Control animals:

no

Results and discussion

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Nine urinary metabolites, namely, N-acetyl-S-[2-(4-ethenylphenyl)-2-hydroxyethyl]-L-cysteine, N-acetyl-S-[1-(4-ethenylphenyl)-2-hydroxyethyl]-L-cysteine, N-acetyl-S-[1-(4-formylphenyl)-2-hydroxyethyl]-L-cysteine, 1-(4-ethenylphenyl)ethane-1,2-diol, 4-ethenylbenzoic acid, 4-ethenylbenzoyl-glycine, 1-ethenyl-4-(1-hydroxyethyl)benzene, 4-(1,2-dihydroxyethyl)benzoic acid, (4-carboxymethylphenyl)acetylglycine, N-acetyl-S-[2-carboxy-1-(4-ethenylphenyl)ethyl]-L-cysteine, and two isomeric beta-D-glucosiduronates derived from 1-(4-ethenylphenyl)ethane-1,2-diol

Applicant's summary and conclusion

Conclusions:

Interpretation of results: low bioaccumulation potential based on study results

Executive summary:

Biotransformation of 1,4-diethenylbenzene in rat was studied. Nine urinary metabolites, namely, N-acetyl-S-[2-(4-ethenylphenyl)-2-hydroxyethyl]-L-cysteine, N-acetyl-S-[1-(4-ethenylphenyl)-2-hydroxyethyl]-L-cysteine, N-acetyl-S-[1-(4-formylphenyl)-2-hydroxyethyl]-L-cysteine, 1-(4-ethenylphenyl)ethane-1,2-diol, 4-ethenylbenzoic acid, 4-ethenylbenzoyl-glycine, 1-ethenyl-4-(1-hydroxyethyl)benzene, 4-(1,2-dihydroxyethyl)benzoic acid, (4-carboxymethylphenyl)acetylglycine, N-acetyl-S-[2-carboxy-1-(4-ethenylphenyl)ethyl]-L-cysteine, and two isomeric beta-D-glucosiduronates derived from 1-(4-ethenylphenyl)ethane-1,2-diol, were isolated and identified by n.m.r. and mass spectrometry.  GC-mass spectral analysis of the methylated urine extract allowed the identification of four other metabolites, as 4-ethenylphenylacetic acid, 4-ethenylphenylacetylglycine, 4-ethenylmandelic acid, and 4-ethenylphenylglyoxylic acid. The structures of the identified metabolites indicate that the main reactive intermediate in the metabolism of 1,4-diethenylbenzene is 4-ethenylphenyloxirane. The first step in the biotransformation of 1,4-diethenylbenzene is the formation of an oxirane. Subsequent steps lead to oxidation of the second ethenyl group leading to the aldehyde N-acetyl-S-[1-(4-formylphenyl)-2-hydroxyethyl]-L-cysteine metabolite. Rats dosed with a single i.p. dose excreted nearly 5.6% of the dose as the glycine conjugate 12, irrespective of the dose. In contrast, the total thioether fraction decreased significantly with increasing dose, being 23 +/- 3, 17 +/- 5 and 12 +/- 1% of dose at 100, 200 and 300 mg/kg, respectively (mean +/- SD).