Glutaral

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Materials and methods

Objective of study:

metabolism

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Glutaral

EC Number:

203-856-5

EC Name:

Glutaral

Cas Number:

111-30-8

Molecular formula:

C5H8O2

IUPAC Name:

glutaraldehyde

Test material form:

liquid

Specific details on test material used for the study:

Non-labelled test material:
Glutaraldehyde 50% aq. solution (Ucarcide 250), from Union Carbide Corporation, purity 50.4%

Labelled test material:
[1,5-14C]-Glutaraldehyde from Midwest Research Institute (Kansas City, MO), radiochemical purity ca. 97%

Radiolabelling:

yes

Remarks:

[1,5-14C]-Glutaraldehyde

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories Inc. (Portage, MI)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

physiological saline

Details on exposure:

The 14C-labelled test substance was mixed with a defined amount of non-labelled test substance and physiological saline; the final dosing solution contained 72 mg glutaraldehyde and 63.5 µCi radioactivity/g. In order to reach a nominal dosage of 60 mg/kg bw, each rat received ca. 250 mg of the dosing solution, corresponding to 16 µCi of radioactivity and 18 mg glutaraldehyde. The mean dosage level obtained was 68.5 mg/kg bw.

Duration and frequency of treatment / exposure:

48 hour(s)

Doses / concentrations

Dose / conc.:

68.5 mg/kg bw (total dose)

No. of animals per sex per dose / concentration:

Four animals

Control animals:

no

Details on dosing and sampling:

Following single application of 0.25 ml test solution, the rats were placed in glass Roth metabolism cages. Air conducted into the cages first passed through traps for removal of moisture and CO2. Air was removed from the cage passed through two consecutive traps for collection of expired CO2 (2-methoxyethanol and ethanolamine 7:3). The CO2 trapping mixture was then sampled for radioactivity determinations at 6, 24 and 48 hours following treatment. Urine and feces were collected separately at 24 and 48 hours following treatment. After 24 hours, the cages were washed with an aqueous solution of 50% acetone and samples of the wash solution were subjected to radioactivity measurements. After 48 hours following treatment, the rats first were anesthetized and blood samples were taken from the abdominal aorta; thereafter they were sacrificed and selected tissues were sampled for radioactivity measurements. The carcasses were solubilized in 10N NaOH and aliquots of the solubilized solution also were subjected to radioactivity measurements.
Radioactivity measurements were conducted using a Searle Analytic Mark III Model 6880 liquid scintillation counter. The aqueous samples were subjected to LSC as such whereas feces and tissue samples were analyzed after having been solubilized according to the method of Yang et al. (J. Agric. Food Chem. 26: 1076-1083, 1978). The separation of radioalabeled compounds excreted in urine was based on anion exchange chromatography.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:

Considering the radioactivity retention in tissues, the highest concentration of radioactivity was found in stomach and kidney. In one animal (the one that showed the most severe symptoms of toxicity including dried red discharge in the periocular and perinasal area; see remark below), increased radioactivity levels also were found in the esophagus and the trachea; according to the authors, this might had resulted from direct contact of the tissue with the test substance during application. Necropsy of the animals revealed in all cases a lesion in the glandular part of the stomach indicative of necrosis (dry, firm leathery appearance)

Details on excretion:

The major radioactivity excretion route for all animals was via the feces whereas only little radioactivity was excreted via CO2 and urine.
Considering the excretion via the feces, in animals that showed symptoms of toxicity, ca. 23% of the radioactivity was eliminated via feces during the first 24 hours following treatment; in contrast, radioactivity excretion via the feces in the one animal that showed no symptoms reached 81% during the same period of time. Furthermore, in the animals that showed symptoms of toxicity, a substantial amount of radioactivity was retained by the carcass. These data indicates that the radioactivity excretion via the feces was affected by the toxicity of the test substance. Considering the excretion via expired CO2, ca. 60% of the elimination happened within the first 6 hours following treatment and 92% were reached within 24 hours (all animals). Similarly, 90% of the radioactivity eliminated via the urine was excreted within the first 24 hours following treatment (all animals). This indicates that in contrast to the feces way, both the CO2 and the urine way of radioactivity excretion, were not affected by the toxicity of the test substance.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

The separation of radioalabeled compounds excreted in urine (anion exchange chromatography) revealed three main fractions respectively corresponding to 22% (so-called neutral fraction), 46% (so-called fraction 17) and to 6% of the recovered radioactivity in the urine.

Any other information on results incl. tables

Radioactivity received by each animal was about 10.9 µCi; the mean amount of test substance was 17.9 mg/animal. Following symptoms of toxicity were seen in ¾ cases and included anorexia, apathy, decreased urine production, and decreased feces production. One of these animals also showed dried red discharge in the periocular and perinasal area indicative of chromodacryorrhea (shedding of bloody tears). One rat remained free of symptoms; the authors suggested that this animal might had had more food in his stomach at treatment time, wherefore possible toxic effects of the administered test substance were neutralized.