2-nitrophenol

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:

other: Meets generally accepted scientific standards, well documented.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Studies in Detoxication 39. Nitro Compounds.

Author:

Robinson D, Smith JN, Williams RT

Year:

1951

Bibliographic source:

Biochem J 50, 221-227

Reference 2

Reference Type:

secondary source

Title:

No information

Author:

Rhone-Poulnec Chimie Courbevoie Cedex

Year:

1977

Bibliographic source:

IUCLID Chemical Data Sheet, edited 2000-02-19

Reference 3

Reference Type:

secondary source

Title:

Toxicological Profile for Nitrophenols: 2-Nitrophenol, 4-Nitrophenol

Author:

ATSDR

Year:

1992

Bibliographic source:

U.S. Department of Health and Human Services, Public Health Service.

Materials and methods

Objective of study:

metabolism

Principles of method if other than guideline:

The metabolism of the purified test substance was analysed in rabbits after gavage of a suspension in water. Metabolite analysis was carried out after isolation from the 24h urine.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-nitrophenol

EC Number:

201-857-5

EC Name:

2-nitrophenol

Cas Number:

88-75-5

Molecular formula:

C6H5NO3

IUPAC Name:

2-nitrophenol

Details on test material:

- Name of test material (as cited in study report): o-Nitrophenol
- Physical state: Solid
- Analytical purity: The commercial product was purified by recrystallisation from ligroin or aqueous ethanol
- m.p. 45 °C

Radiolabelling:

no

Test animals

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

no data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

no data

Duration and frequency of treatment / exposure:

Single administration

Doses / concentrations

Remarks:

Doses / Concentrations:
- For the determination of the excreted free or conjugated test substance: 200 mg/kg bw (3 animals), and 450 mg/kg bw (1 animal)
- For the determination of the excreted amino derivates of the test substance: 330 mg/kg bw (3 animals)
- For the determination of the excreted glucuronic acid and ethereal sulphate conjugations of the test substance: 200 mg/kg bw (3 animals)

No. of animals per sex per dose / concentration:

3 rabbits per dose (not further specified)

Control animals:

not specified

Details on study design:

Rabbits were treated with an aqueous suspension of the test material via gavage. 24 h urine was sampled and analysed for free and conjugated test substance, as well as for the reduction of the nitro group and the oxidation of the test substance. Furthermore, ß-glucuronides and ethereal sulphates of the test substance have been isolated from the urine and quantitatively analysed.

Results and discussion

Main ADME results

Main ADME results 1

Type:

metabolism

Results:

nitrophenylglucuronides (70 %), ethereal sulphates (10 %), reduced nitro group (6 %), nitroquinol (< 1 %)

Main ADME results 2

Type:

excretion

Results:

renal pathway (80-90 % within 24 hours)

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

At least 80-90 % of the test substance was excreted within 24 hours. The test substance was excreted in conjugated forms, there being only small amounts (<1 %) of the unchanged free phenol excreted. The main metabolites were the nitrophenylglucuronides which account for about 70 % of the dose. The corresponding ethereal sulphates were also excreted (about 10 %). The nitro group of the test substance underwent reduction in vivo only to a minor extent, and most of it was excreted unchanged. The extent of reduction was about 6 %. The test substance also underwent oxidation to a very small extent (<1 %) and yielded traces of nitroquinol. The dihydric phenol produced was similar to those formed during the Elbs persulphate oxidation of the test substance. There was a significance of the similarity in relation to free radicals. The ß-glucuronides of the test substance were isolated and characterised as triacetyl ß-o-nitrophenyl-D-glucuronide and its methyl ester.