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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
1966
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented, meets generally accepted scientific principles, acceptable for assessment
Cross-reference
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Excretion of certain polyethylene glycol ether adducts of nonylphenol by the rat
Author:
Knaak JB, Eldrige Jane M and Sullivan LJ
Year:
1966
Bibliographic source:
Toxicol. Appl. Pharmacol. 9:331-340

Materials and methods

Objective of study:
excretion
Principles of method if other than guideline:
The study was conducted to evaluate the excretion of the test substances in urine, feces and CO2 and analysed using chromatographic methods.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Test substance 1: Nonylphenol-14C (NP-14C ); test substance 2: Nonylphenol-14C TP-9 (NP-14C TP-9); test substance 3: Isolated ethylene-14C oxide TP-9 fractions representing adduct numbers of 7, 10, 12, and 15
- Radiochemical purity (if radiolabelling): Yes
- Specific activity (if radiolabelling): Test substance 1: 1.0 µc/mg; test substance 2: 0.3 µc/mg; test substance 3: Not reported
- Locations of the label (if radiolabelling): Test substance 1 and 2: at the carbon in the NP group; test substance 3: at the carbon in ethylene oxide group
Radiolabelling:
yes

Test animals

Species:
rat
Strain:
other: carworth farms-elias stock
Sex:
male
Details on test animals and environmental conditions:
Body weight: 150 g

No further details reported.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Propylene glycol for test substance 1 and water for test substance 1 and 2
Details on exposure:
Dosing solution details:
- 1 mg of test substance 1 was administered orally or intraperitoneally to 150 g male rats in 500 mg of propylene glycol (i.e., equivalent to 6.7 mg/kg bw) .
- 10 mg of test substance 2 and 3 were administered to 150 g male rats in 990 mg of water (i.e., equivalent to 67 mg/kg bw).
Duration and frequency of treatment / exposure:
Single dose
Doses / concentrations
Remarks:
Doses / Concentrations:
- Test substance 1: 6.7 mg/kg bw
- Test substance 2 and 3: 67 mg/kg bw
No. of animals per sex per dose:
4
Control animals:
not specified
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Excretion and metabolites characterisation)
- Tissues and body fluids sampled: Urine, faeces, cage washes, caracasess and/or CO2
- Time and frequency of sampling: Daily for 14C in urine and faeces over a 7-day period and for 14C in CO2 over a 4-day period for all the three samples; at termination for 14C in carcasses for test substance 3.
- Method type(s) for identification: Gas chromatography for nonylphenol; thin layer chromatography for TP-9, ion-exhange chromatography for the metabolites


Results and discussion

Main ADME resultsopen allclose all
Type:
excretion
Results:
20% of the test substance 1 and 2 was excreted in urine, 78% in faeces (within 7 d period) and none in CO2 (within 4 d period)
Type:
excretion
Results:
85, 90, 88 and 85% was excreted in urine and feces while 3.3, 1.2, 0.78, 0.20 and 1.2% was excreted in 14CO2 for 7-, 10-, 12-, and 15- mole adducts of test substance 3 respectively.

Toxicokinetic / pharmacokinetic studies

Details on excretion:
-Test substance 1 (i.e., 14C-NP): 20% in urine, 78% in faeces (over 7 d period) and none in CO2 (over 4 d period)
-Test substance 2 (i.e., NP-14C TP-9): 20% in urine, 78% in faeces (over 7 d period) and none in CO2 (over 4 d period)
-Test substance 3 (i.e., the isolated ethylene 14C oxide TP-9 fractions representing adduct numbers of 7, 10, 12 and 15): 85, 90, 88 and 85% was excreted in urine and feces while 3.3, 1.2, 0.78, 0.20 and 1.2% was excreted in 14CO2 for 7-, 10-, 12-, and 15- mole adducts respectively (refer to attached document for details).

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
The major urinary metabolites were found to be mono- and dicarboxylic acids of polyethylene glycol and the glucuronic acid conjugates of nonylphenol by ion-exchange chromatographic.

Any other information on results incl. tables

Other findings:

The carcasses of animals administered test substance 2 and 3 were examined for 14C residues and were found to be free of detectable radioactivity.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
Under the condition of the study, the rat excreted both 14C-NP and NP-14C TP-9 as 20% in urine and 78% in feces and none in CO2 indicating an oral absorption of about 20%. Further, the 12- and 15-mole adducts of isolated ethylene 14C oxide TP-9 fractions were excreted to a greater extent in the feces than the 7- and 10-mole adducts and the reverse situation occurred in urine.
Executive summary:

A study was conducted to evaluate the excretion of NP-14C TP-9, 14C-NP and the isolated ethylene 14C oxide TP-9 fractions representing adduct numbers of 7, 10, 12 and 15 in male rats.

 

1 mg of 14C-NP was administered orally or intraperitoneally to 150 g weighing male rats in 500 mg of propylene glycol (i.e., equivalent to 6.7 mg/kg bw). While, 10 mg of NP-14C TP-9 and isolated ethylene 14C oxide TP-9 fractions were administered to 150 g male rats in 990 mg of water (i.e., equivalent to 67 mg/kg bw). Then the daily urine and fecal samples collected over 7 d period as well as CO2 samples collected over a 4 d period were analysed for the 14C. At termination caracasses from the animals administered NP-14C TP-9 and isolated ethylene 14C oxide TP-9 fractions was also analysed for 14C.

Within 7 days, the rat excreted both 14C-NP and NP-14C TP-9 as 20% in urine and 78% in faeces. However, there was no excretion in CO2when analysed over a 4 d period. Regarding the isolated ethylene 14C oxide TP-9 fractions, the 12- and 15-mole adducts were excreted to a greater extent in the feces than the 7- and 10-mole adducts and the reverse situation occurred in urine.

The major urinary metabolites analysed by ion exchange chromatography were found to be mono- and dicarboxylic acids of polyethylene glycol and the glucuronic acid conjugates of nonylphenol. 

Under the condition of the study, the rat excreted both 14C-NP and NP-14C TP-9 as 20% in urine and 78% in feces and none in CO2 indicating an oral absorption of about 20%. Further, the 12- and 15-mole adducts of isolated ethylene 14C oxide TP-9 fractions were excreted to a greater extent in the feces than the 7- and 10-mole adducts and the reverse situation occurred in urine (Knaak et al., 1966).