2,3-xylenol

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Data is from peer-reviewed journal

Data source

Reference

Reference Type:

publication

Title:

Metabolism of Derivatives of Toluene 5. The fate of the Xylenols in the rabbit, with further observations on the metabolism of the xylenes

Author:

H. G. Bray, Brenda G. Humphris and W. V. Thorpe

Year:

1950

Bibliographic source:

Biochem. J. 4.7: 395-399

Materials and methods

Objective of study:

metabolism

Test guideline

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

In Vivo metabolism study of 2,3-dimethylphenol in rabbit

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

2,3-xylenol

EC Number:

208-395-3

EC Name:

2,3-xylenol

Cas Number:

526-75-0

Molecular formula:

C8H10O

IUPAC Name:

2,3-xylenol

Details on test material:

- Name of test material (as cited in study report): 2,3-dimethylphenol
- Molecular formula (if other than submission substance): C8H10O
- Molecular weight (if other than submission substance): 122.166 g/mole
- Substance type: Organic
- Physical state: No data available
- Impurities (identity and concentrations): No data available

Specific details on test material used for the study:

- Name of test material (as cited in study report): 2,3-dimethylphenol
- Molecular formula (if other than submission substance): C8H10O
- Molecular weight (if other than submission substance): 122.166 g/mole
- Substance type: Organic
- Physical state: No data available
- Impurities (identity and concentrations): No data available

Radiolabelling:

not specified

Test animals

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: No data available
- Age at study initiation:No data available
- Weight at study initiation: 2-3 kg.
- Fasting period before study:No data available
- Housing:No data available
- Diet (e.g. ad libitum): rabbit pellets, ad libitum
- Water (e.g. ad libitum):Water, ad libitum
- Acclimation period:No data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C):No data available
- Humidity (%):No data available
- Air changes (per hr):No data available
- Photoperiod (hrs dark / hrs light):No data available

IN-LIFE DATES: From: To:No data available

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

2,3-dimethylphenol were administered by stomach tube as suspensions in water.

Duration and frequency of treatment / exposure:

No data available

Doses / concentrations

Dose / conc.:

1 000 mg/kg bw/day

No. of animals per sex per dose / concentration:

No data available

Control animals:

not specified

Positive control reference chemical:

No data available

Details on study design:

No data available

Details on dosing and sampling:

No data available

Statistics:

No data available

Results and discussion

Preliminary studies:

No data available

Main ADME results

Main ADME results 1

Type:

absorption

Results:

No data available

Main ADME results 2

Type:

distribution

Results:

No data available

Main ADME results 3

Type:

metabolism

Results:

Metabolism taks plase by O-conjugates and give , ethereal sulphate, ester glucuronide, ether glucuronide and ether-soluble acid

Main ADME results 4

Type:

excretion

Results:

excreted in urine

Toxicokinetic / pharmacokinetic studies

Details on absorption:

No data available

Details on distribution in tissues:

No data available

Details on excretion:

1% free non-acidic phenol, 13% ethereal sulphate, 1 % ester glucuronide, 50 % ether glucuronide and 69 % ether-soluble acid were recovered in urine

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

The major portion of the dose (77-93 %) being excreted as O-conjugates. the values for ether glucuronide are somewhat lower than those for the ether-soluble acid. This difference probably arises from decomposition occurring during the preliminary hydrolysis which case the crystals obtained were shown by comparison is carried out in 5N-sulphuric acid.

Any other information on results incl. tables

Excretion of metabolites of xylenols in the rabbit

		Excretion
2:3-Xylen-1-ol	No. Of Experiments	Range (%)	Average (%)
Free non-acidic phenol	4	0-4-1-6	1
Ethereal sulphate	3	11-14	13
Ester glucuronide	6	0-3	1
Ether glucuronide	6	37-69	50
Ether-soluble acid	6	55-86	69

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): low bioaccumulation potential based on study results
On the basis of observed result it is concluded that 2,3-dimethylphenol show O-conjugates metabolism and excreted in the form of ethereal sulphate, ester glucuronide, ether glucuronide and ether-soluble acid in urine. Hence, expected to have Low bio-accumulation potential based on study results. 

Executive summary:

In a in vivo metabolism study, rabbit were treated with 2,3-dimethylphenol orally by gavage at 1000 mg. It was observed that 2,3-dimethylphenol were excreted as O-conjugates by preliminary hydrolysis which case the crystals obtained were shown by comparison is carried out in 5N-sulphuric acid. 1% free non-acidic phenol, 13% ethereal sulphate, 1 % ester glucuronide, 50 % ether glucuronide and 69 % ether-soluble acid were recovered in urine.Therefore, On the basis of observed result it is concluded that 2,3-dimethylphenol show O-conjugates metabolism and excreted in the form of ethereal sulphate, ester glucuronide, ether glucuronide and ether-soluble acid in urine. Hence, expected to have Low bio-accumulation potential based on study results.