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Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
No information, study reported in 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Secondary source: review of the information available on the health and environmental effects of Terephthalic acid.

Data source

Reference
Reference Type:
review article or handbook
Title:
Unnamed
Year:
1984

Materials and methods

Objective of study:
absorption
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Literature review
GLP compliance:
no
Remarks:
: not applicable

Test material

Constituent 1
Chemical structure
Reference substance name:
Terephthalic acid
EC Number:
202-830-0
EC Name:
Terephthalic acid
Cas Number:
100-21-0
Molecular formula:
C8H6O4
IUPAC Name:
terephthalic acid
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
[14C-carboxyl]-terephthalic acid
Specific details on test material used for the study:
[14C-carboxyl]-terephthalic acid
Radiolabelling:
yes
Remarks:
[14C-carboxyl]-terephthalic acid

Test animals

Species:
rat
Strain:
other: a variety of strains were used
Sex:
male/female
Details on test animals or test system and environmental conditions:
In Hoshi and Kuretani (1967), five female Wistar rats were used.
Wolkowski-Tyl et al (1982a) used F344 rats.
Moffitt et al (1975) used CR rats.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on exposure:
No further information
Duration and frequency of treatment / exposure:
In Hoshi and Kuretani (1967) , the test compound was administered to groups of five rats as a suspension in a 0.5% sodium carboxymethylcellulose. The test animals were given a single gavage dose of 85 mg/kg.

In Wolkowski-Tyl et al (1982a), a single dose of the radiolabelled compound was administered to the rats by gavage.

Moffitt et al (1975), radiolabelled test substance administered by gavage. In the oral experiment, groups of five rats received single or repeated (5 doses over 10 days, alternate days). Also given unlabelled test substance in 0, 40 or 80 mg.
Doses / concentrations
Remarks:
Doses / Concentrations:
Hoshi and Kuretani (1967); the test animals were given a single gavage does of 85 mg/kg.
Wolkowski-Tyl et al (1982a); a single dose given by gavage or i.v. injection.
Moffitt et al (1975); single or repeated doses of 40 mg 14C terephthalic acid along with 0, 40 or 80 mg of unlabelled terephthalic acid in peanut oil.
No. of animals per sex per dose / concentration:
No details
Control animals:
no
Positive control reference chemical:
No information
Details on study design:
Hoshi and Kuretani (1967);The compound was administered to groups of five rats as a suspension in a 0.5% sodium carboxymethylcellulose. The test animals were given a single gavage does of 85 mg/kg. The esophagus, stomach, small intestine, caecum and large intestine of rats were assayed for radioactivity 2, 4, 6, 8, 24 and 48 hours after administration. Urine and faeces were collected from treated rats after 8, 24 and 48 hours and assayed for radioactivity. In a second study using the same species, dose and method of administration, Hoshi and Kuretani (1968) assessed the distribution of radioactivity by killing the animals and taking blood and tissues samples at 2, 4, 6, 8, 24 and 48 hours.

Wolkowski-Tyl et al (1982a) studied the absorption and distribution by giving the test animal a single dose of radiolabelled compound in aqueous 0.5% sodium carboxymethylcellulose. The dose was given by gavage to rats fasted for 12 hours. The radioactivity in the plasma was monitored up to 400 hours after administration. The test substance was also administered by i.v. injection and the distribution of the test substance assessed by taking blood samples at selected intervals up to 400 minutes.

Moffitt et al (1975); groups of five rats received single or repeated (5 doses over 10 days) doses of 40 mg of radiolabelled terephthalic acid. The urine and faeces were collected and the repeated dose animals were killed on day 10 of the experiment at which time their organs were assayed for radioactivity.
Details on dosing and sampling:
oshi and Kuretani (1967);The compound was administered to groups of five rats as a suspension in a 0.5% sodium carboxymethylcellulose. The test animals were given a single gavage does of 85 mg/kg. The esophagus, stomach, small intestine, caecum and large intestine of rats were assayed for radioactivity 2, 4, 6, 8, 24 and 48 hours after administration. Urine and faeces were collected from treated rats after 8, 24 and 48 hours and assayed for radioactivity. In a second study using the same species, dose and method of administration, Hoshi and Kuretani (1968) assessed the distribution of radioactivity by killing the animals and taking blood and tissues samples at 2, 4, 6, 8, 24 and 48 hours.

Wolkowski-Tyl et al (1982a) studied the absorption and distribution by giving the test animal a single dose of radiolabelled compound in aqueous 0.5% sodium carboxymethylcellulose. The dose was given by gavage to rats fasted for 12 hours. The radioactivity in the plasma was monitored up to 400 hours after administration. The test substance was also administered by i.v. injection and the distribution of the test substance assessed by taking blood samples at selected intervals up to 400 minutes.

Moffitt et al (1975); groups of five rats received single or repeated (5 doses over 10 days) doses of 40 mg of radiolabelled terephthalic acid. The urine and faeces were collected and the repeated dose animals were killed on day 10 of the experiment at which time their organs were assayed for radioactivity.
Statistics:
No information

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Hoshi and Kuretani (1967); Expired air and faeces collected for 24 hours accounted for less than 0.04 and 3.3% of the total radioactivity administered respectively.  Twenty-four hours after administration, the urine, faeces and expired air accounted for 93.5, 3.3 and less than 0.04% of the radioactivity administered. Within 48 hours, the majority of the dose had been excreted. After 48 hours, the integrated excretion of radioactivity in the urine and faeces was 93.8 and 3.3%. In a previous experiment, Hoshi and Kuretani (1965) had found that when a dose was given by i.p. injection, most of the dose was recovered quantitatively in the urine after 24 hours. 
 
Wolkowski-Tyl et al (1982a); it was observed that radioactivity appeared in the plasma of treated rats in less than 25 minutes and declined slowly for up to 400 minutes after dosing. The dose was given by both gavage and i.v. injection. After injection of14C-terephthalic acid in an aqueous buffer solution, blood samples were drawn from the jugular veins and assayed for radioactivity at selected intervals. The data obtained gave a half life of 1.2 hours and average volumes of distribution as 107.3 and 1312.7 ml/kg for plasma and all compartments. When rats were given the compound by gavage, a longer terminal half-life was observed which indicated that absorption or dissolution of terephthalic acid from the gut maybe partially rate limiting. 
 
Moffitt et al (1975) concluded on the basis of excretion studies that terephthalic acid was rapidly absorbed regardless of the dose by oral or inhalation routes in rats. In the single dose experiments, >80% of the administered radioactivity was excreted in the urine and faeces within 48 hours of administration; the excreted radioactivity appeared to be evenly distributed between the faeces and urine. The organs of the rats were also analysed for radioactivity. Results indicated that radioactivity present in the blood, liver, lung, heart, kidney, spleen, adrenals, pancreas, testes and brain accounted for less than 0.1% of the total dose regardless of the amount. Repeated administration of the compound by intratracheal instillation gave similar results. 
Details on distribution in tissues:
No details
Transfer into organs
Observation:
not determined
Details on excretion:
No information
Toxicokinetic parameters
Toxicokinetic parameters:
other: no information

Metabolite characterisation studies

Metabolites identified:
no

Any other information on results incl. tables

Hoshi and Kuretani (1967); Expired air and faeces collected for 24 hours accounted for less than 0.04 and 3.3% of the total radioactivity administered respectively.  Twenty-four hours after administration, the urine, faeces and expired air accounted for 93.5, 3.3 and less than 0.04% of the radioactivity administered. Within 48 hours, the majority of the dose had been excreted. After 48 hours, the integrated excretion of radioactivity in the urine and faeces was 93.8 and 3.3%. In a previous experiment, Hoshi and Kuretani (1965) had found that when a dose was given by i.p. injection, most of the dose was recovered quantitatively in the urine after 24 hours. 

 

Wolkowski-Tyl et al (1982a); it was observed that radioactivity appeared in the plasma of treated rats in less than 25 minutes and declined slowly for up to 400 minutes after dosing. The dose was given by both gavage and i.v. injection. After injection of14C-terephthalic acid in an aqueous buffer solution, blood samples were drawn from the jugular veins and assayed for radioactivity at selected intervals. The data obtained gave a half life of 1.2 hours and average volumes of distribution as 107.3 and 1312.7 ml/kg for plasma and all compartments. When rats were given the compound by gavage, a longer terminal half-life was observed which indicated that absorption or dissolution of terephthalic acid from the gut maybe partially rate limiting. 

 

Moffitt et al (1975) concluded on the basis of excretion studies that terephthalic acid was rapidly absorbed regardless of the dose by oral or inhalation routes in rats. In the single dose experiments, >80% of the administered radioactivity was excreted in the urine and faeces within 48 hours of administration; the excreted radioactivity appeared to be evenly distributed between the faeces and urine. The organs of the rats were also analysed for radioactivity. Results indicated that radioactivity present in the blood, liver, lung, heart, kidney, spleen, adrenals, pancreas, testes and brain accounted for less than 0.1% of the total dose regardless of the amount. Repeated administration of the compound by intratracheal instillation gave similar results. 

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
Terephthalic acid has been observed to be rapidly absorbed when administered orally or by intratracheal instillation. It is readily excreted unchanged in the urine and faeces. Results of adsorption in the tissues indicated that radioactivity present in the blood, liver, lung, heart, kidney, spleen, adrenals, pancreas, testes and brain accounted for <0.1% of the total dose regardless of the amount. Repeated administration of the compound by intratracheal instillation gave similar results. 
Executive summary:

The results of studies reviewed by the EPA indicate that terephthalic acid is rapidly absorbed following oral or intratracheal administration and is rapidly excreted in the urine. There is no indication of bioaccumulation.