1,2-benzenedicarboxylic acid, di-C10-12-branched alkyl esters

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study report which meets basic scientific principles: pre-GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1972

Report date:

1972

Materials and methods

Objective of study:

metabolism

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Animals received "cold" compound daily for five days. On the sixth day, each animal received a single dose of "hot" compound and placed in metabolism cages for 72 hours.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,2-Benzenedicarboxylic acid, di-C8-10-branched alkyl esters, C9-rich

EC Number:

271-090-9

EC Name:

1,2-Benzenedicarboxylic acid, di-C8-10-branched alkyl esters, C9-rich

Cas Number:

68515-48-0

IUPAC Name:

bis(7-methyloctyl) phthalate

Details on test material:

[14C] DINP (CAS 68515 -48 -0)

Radiolabelling:

yes

Remarks:

C14 labeled DINP, 105 uCi/g

Test animals

Species:

rat

Strain:

not specified

Sex:

male

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Duration and frequency of treatment / exposure:

Animals received "cold" compound daily for five days. On the sixth day, each animal received a single dose of "hot" compound and placed in metabolism cages for 72 hours.

Doses / concentrations

Remarks:

Doses / Concentrations:
0.5 ml ("cold" and "hot")

No. of animals per sex per dose / concentration:

5 male animals

Control animals:

no

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:

No tissue studied had over 0.001% per gram of the administered dose. On a total sample basis, residual amounts of radioactivity were found in the gastrointestinal tract of each animal. Of the selected organs which were analyzed, the liver contained the most radioactivity, 0.010% (mean). Most of the radioactivity retained by the animals was found in the carcass and remaining viscera. Each animal retained an amount of the administered dose in the carcass and remaining viscera which was close to the average value of 0.060%. The value for the average amount retained after 72 hours is 0.09% of the administered dose.

Details on excretion:

The amount excreted in the urine within 72 hours ranged from a high of 18.34% to a low of 8%. The majority of radioactivity found was excreted in the first collection (12 hr). Thereafter, the amount of radioactivity found fell off rapidly so that by the 72-hours collection, less than 0.1% of the dose was found. In all test animals, over 80% of the administered dose was excreted in the feces, and most of that radioactivity was excreted within 24 hours after dosing. Between the 60 and 72-hour post dosage period, no animal excreted over 0.2% of the administered dose.

Applicant's summary and conclusion

Executive summary:

This study was designed to assess the extent of gastrointestinal absorption, the distribution in selected tissues, and the rate and routes of excretion of [14C] DINP (CAS 68515 -48 -0) following oral administration to male albino rats weighing approximately 200 grams each (4 treated rats, 2 controls). Four animals received 0.5 ml of "cold" compound daily for five days and on the sixth day, they were dosed via oral intubation with 0.5 ml of "hot" compound (about 2,500 mg/kg/d). Expired gases, fecal and urinary excreta were collected separately, at 12 hours intervals, during the entire study period (72 hours). Recordings were made of animal appearance and behaviour, body weights, volumes of urine excreted, weights of feces excreted, and amounts of food consumed. Seventy-two hours after intubation, the animals were sacrificed and gross pathological observations were made. Blood and urine remaining in the bladder were collected. The hearts, livers, kidneys, intestines, stomachs and aliquots of fat and muscle were removed and weighed. The contents of the intestines and stomach were separated from their respective walls. The remaining viscera and carcass from each animal were combined and weighed.

 

During the six-day period, all the animals exhibited a normal behaviour. All animals gained weight during the five-day period when they were given the cold compound. During the 72 hours after the administration of the "hot" compound, one test animal and one control animal lost weight, and the test animals consumed more food and excreted more feces than the controls, but the controls excreted more urine than the test animals.

 

The amount of compound excreted in the urine within 72 hours ranged from 8% to 18.34% of the administered dose. The majority of the radioactivity found was excreted in the first collection (12 hours). Thereafter, the amount of radioactivity found fell off rapidly so that by the 72-hour collection period less than 0.1% of the dose was found in all animals except in one animal.

 

Over 80% of the administered dose was excreted in the feces and most of the radioactivity was excreted within 24-hours after dosing. Between the 60- and 72-hour postdosage period no animal excreted over 0.2% of the administered dose.

 

At sacrifice the tissues and organs of all animals appeared normal when examined for gross pathological conditions. No tissue studied had over 0.001% per gram of the administered dose. On a total sample basis, residual amounts of radioactivity were found in the gastrointestinal tract of each animal. Of the selected organs, the liver contained the most radioactivity (i.e. 0.010% mean). Most of the radioactivity retained by the animals was found in the carcass and remaining viscera (i.e. 0.060% of the administered dose).

 

No expired [14C] DINP was detected.