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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1992
Reference Type:
study report
Title:
Unnamed
Year:
1992

Materials and methods

Objective of study:
other: ADME
Test guideline
Guideline:
other: not further specified
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
Name of test material (as cited in study report): Acetyl tributyl citrate (CAS RN 77-90-7)
Analytical purity: 99.02 %
Radiochemical purity (if radiolabelling): 100 %
Radiolabelling:
yes
Remarks:
14C

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
Absorption and elimination study: 4 m
Rate of absorption study: 5 m

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Duration and frequency of treatment / exposure:
single oral dosing
Doses / concentrations
Remarks:
Doses / Concentrations:
70 mg [14C]ATBC/kg bw
No. of animals per sex per dose:
4 - 5
Control animals:
not specified
Details on dosing and sampling:
Urine, faeces, cage wash, expired organics and [14C]CO2, blood, tissues (including GI tract and contents) and carcass were analysed for [14C] and/or unchanged ATBC
Statistics:
no data

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
see below
Details on distribution in tissues:
see below
Details on excretion:
see below

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
At least 9 radiolabeled metabolites were found in urine and 3 in faeces. Urinary metabolites positively identified were acetyl citrate, mono-butyl citrate (tentatively the major metabolite), acetyl mono-butyl citrate, dibutyl citrate, and acetyl dibutyl citrate.

Any other information on results incl. tables

Absorption of dosed [14C] was rapid (t1/2 = 1.0 h) and extensive (>= 67 %). Absorbed [14C]ATBC was rapidly and completely metabolized and eliminated. More than 87 % of the administered radioactivity was excreted during the initial 24 hrs after dosing. For [14C] in blood an elimination half-life of 3.4 hrs was calculated during this interval. Less than 1 % of the dosed radioactivity remained in tissues and carcass 48 hrs post-dosing.

The principle route of [14C] excretion was via urine (59 – 70 % of the [14C] dose), while 25 – 36 % were excreted via faeces and 2 % as [14C]CO2.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
After oral gavage, ATBC is rapidly absorbed, metabolized and excreted by rats.
Executive summary:

In this study groups of 4 – 5 male Sprague-Dawley rats were dosed once via gavage with 70 mg [14C]ATBC/kg bw and urine, faeces, cage wash, expired organics and [14C]CO2, blood, tissues (including GI tract and contents) and carcass were analysed for [14C] and/or unchanged ATBC.

Absorption of dosed [14C] was rapid (t1/2 = 1.0 h) and extensive (>= 67 %). Absorbed [14C]ATBC was rapidly and completely metabolized and eliminated. More than 87 % of the administered radioactivity was excreted during the initial 24 hrs after dosing. For [14C] in blood an elimination half-life of 3.4 hrs was calculated during this interval. Less than 1 % of the dosed radioactivity remained in tissues and carcass 48 hrs post-dosing.

The principleroute of [14C] excretion was via urine (59 – 70 % of the [14C] dose), while 25 – 36 % were excreted via faeces and 2 % as [14C]CO2. At least 9 radiolabeled metabolites were found in urine and 3 in faeces. Urinary metabolites positively identified were acetyl citrate, mono-butyl citrate (tentatively the major metabolite), acetyl mono-butyl citrate, dibutyl citrate, and acetyl dibutyl citrate.

It was concluded that the low oral toxicity of ATBC is not due to poor absorption but is caused by an intrinsic property of ATBC and/or its metabolites or is due to rapid clearance in the rat.