Naphthalene-1,5-disulphonic acid

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Non-GLP japanese study which did not follow an OECD guideline.

Data source

Reference

Reference Type:

publication

Title:

Studies on the Absorption, Excretion, Distribution and Metabolism of (2-Acetyllactoyloxyethyl)trimethylammonium 1,5-naphtalenedisulfonate (TM-723)

Author:

Nakashima, Y. et al.

Year:

1979

Bibliographic source:

Oyo Yakuri. Sendia. Vol 18, ISS 5, 1979, 723-748

Materials and methods

Objective of study:

other: ADME

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The absorption, excretion, distribution and metabolism of 2-acetyllactoyloxyethyl)trimethylammonium-1,5-naphtalendisulfonate (TM-723) was studied in rats and mice with 14C and 3H-labelled derivates of the compound and its potentially possible metabolites after intravenous, subcutaneous and peroral administration. Results of the tritium labelled sodium salt of 1,5-naphtalenedisulfonate and the tritium labelled 2-Acetyllactoyloxyethyl)trimethylammonium salt of 1,5-naphtalenedisulfonate are presented in the following.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Naphthalene-1,5-disulphonic acid

EC Number:

201-317-9

EC Name:

Naphthalene-1,5-disulphonic acid

Cas Number:

81-04-9

Molecular formula:

C10H8O6S2

IUPAC Name:

naphthalene-1,5-disulfonic acid

Test material form:

solid: crystalline

Details on test material:

Unspecified test material

Radiolabelling:

yes

Remarks:

(3H-naphtalenedisulfonate)TM-723 (named 3H-TM-723) and (3H-sodium-naphtalenedisulfonate)TM-723 (named 3H-TM-723D-Na)

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

other: intravenous, subcutaneous, peroral

Vehicle:

not specified

Duration and frequency of treatment / exposure:

Single dose

Doses / concentrations

Remarks:

Doses / Concentrations:
12.7 mg/kg bw (3H-TM-723D-Na) and 25 mg/kg bw (3H-TM-723)

No. of animals per sex per dose / concentration:

No data

Control animals:

no

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

After oral administration of 12.7 mg/kg bw 3H-TM-723D-Na (p.o.) low blood level (<1µg/mL) were reported compared to intravenous (i.v.:~12 µg/mL) and subcutaneous (s.c) application (maximum 5 µg/mL within 0.75 h). Blood level after i.v. and s.c. application decreased to below 1 µg/mL within 2 h indicating rapid tissue distribution or elimination. Excretion after i.v. and s.c application was mainly via urine (>90% within 24 h) while excretion via urine after p.o. application was only 14.5% within 24 h (14.8% within 120 h) for 3H-TM-723D-Na and 16.9% within 24 h (18.3% within 120 h) for 3H-TM-723. After oral application the majority was excreted via feces (85.3% for 3H-TM-723D-Na and 82.0% for 3H-TM-723). Thus, the low blood level and the lower excretion rate in urine after oral application indicate an incomplete absorption of the sodium and the 2- acetyllactoyloxyethyl)trimethylammonium salt of 1,5-naphtalenedisulfonic acid (Armstrongs acid).

Details on distribution in tissues:

Residual radioactivity (3H-TM-723D-Na) was predominantly found in the kidney after intravenous (10 minutes) and subcutaneous (30 minutes) application of the radiolabeled test material. In addition, residual radioactivity was also present in lower amount in blood plasma and liver (10 min i.v. and 30 min s.c.). Nevertheless, residual radioactivity could be detected in low extent in more or less almost all tissues within 10 min after i.v. and 30 min after s.c. application of the test material indicating rapid tissue distribution. Peroral application revealed only very limited residual radioactivity (60 minutes) in some tissues (kidney, liver, heart, lung, blood and plasma) compared to i.v. and s.c. application of the test material indicating low oral absorption. Moreover, tissue accumulation is not likely. Pregnant rats administered with radio-labelled 3H-TM-723D-Na (i.v.) showed a similar tissue distribution pattern compared to non-pregnant rats after 10 and 60 minutes. Residual activity was mainly detected in kidney, maternal plasma, blood, liver, stomach and ovarium 10 minutes after application of the test material indicating rapid tissue distribution. In addition, residual radioactivity was also recorded in placenta, amniotic fluid, fetus (liver, kidney, GI tract) indicating that 3H-TM-723D-Na passes the placenta barrier.

Details on excretion:

The absorbed radioactivity was predominately excreted with the urine, accounting for >90% (i.v.) and >95% (s.c.) within 24 hours after administration of the radiolabeled test material. Very low amounts of the absorbed radioactivity were excreted with the feces, accounting for less than 4% (i.v.) and 2.2% (s.c.) within 24 hours after administration of the test material. In contrast, the major part of the radioactivity (approximately 81% of administered dose) was excreted with the feces within 24 hours after peroral (p.o.) administration of the radio-labeled test material, whereas only 15% of the absorbed radioactivity was excreted with the urine at the same time, indicating only limited absorption of the administered test material. After 5 days the complete dose was excreted, accounting totally for 99.7% (i.v.), 101.6% (s.c.) and 100.1% (p.o.) of the administered dose in rats, respectively. Biliary excretion of 3H after i.v. and p.o. application of 3H-TM-723D-Na was low (0.5 and 0.14% of applied dose, respectively).

Metabolite characterisation studies

Metabolites identified:

no