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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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented, acceptable publication

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1995
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report date:
1993

Materials and methods

Objective of study:
toxicokinetics
Principles of method if other than guideline:
Disposition and metabolism of Acrylic acid (AA) in C3H mice after single oral administration.
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Acrylic acid
EC Number:
201-177-9
EC Name:
Acrylic acid
Cas Number:
79-10-7
Molecular formula:
C3H4O2
IUPAC Name:
acrylic acid
Details on test material:
- Name of test material (as cited in study report): Acrylic acid
- Analytical purity: > 98 % (unlabeled AA)
- Supplier: Union Carbide Corporation

- Radiochemical purity (if radiolabelling): >= 98.6 %
- Specific activity (if radiolabelling): 0.14 - 0.4 mCi/mmol
- Locations of the label (if radiolabelling): [1-14C]AA
- Supplier: Sigma Chemical Co. (St. Louis, Mo.)
Radiolabelling:
yes

Test animals

Species:
mouse
Strain:
C3H
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories (Kingston, NY)
- Substrain: C3H/HeNCrlBR
- Age at study initiation: approx. 35 d old
- Weight at study initiation: 21 g
- Diet (ad libitum): Agway Prolab Diet Mouse, Agway Inc., Syracuse, NY
- Water (ad libitum)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
- Vehicle: Milli-Q filtered water at a final concentration of 4 or 15 mg/mL
- Dosing volume: 10 mL/kg bw
Duration and frequency of treatment / exposure:
once
Doses / concentrations
Remarks:
Doses / Concentrations:
40 and 150 mg/kg bw
No. of animals per sex per dose / concentration:
15
Control animals:
no
Details on study design:
- Dose selection rationale: The oral dose of 40 mg/kg bw was selected for comparison to previous work on the disposition of [2,3-14C]AA in Sprague-Dawley rats (de Bethizy et al. 1987) and the 150 mg/kg bw dose was selected since a similar oral dose induced slight, acute gastric irritation in Fischer 344 rats (Ghanayem et al. 1985).
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, faeces, blood, plasma, stomach contents (after sacrifice)
- Time and frequency of sampling: Urine was collected under dry ice and faeces were collected at room temperature at 8, 24, 48, and 72 h. At 1 and 8 hrs, 5 animals from ech group were sacrificed and blood samples collected. Tissues were sampled at termination (liver, kidney, fat, stomach).
- Traps for volatile compounds:
Room air was drawn through the metabolism cages at a rate of approximately 350 mL/min. Expired 14CO2 was collected in traps containing a solution of 2-methoxyethanol : ethanolamine (7:3, v/v), which was replaced with fresh solution at regular intervals. Other exhaled volatile 14C-labeled organic compounds were collected onto activated charcoal traps (approximately 4 g) placed in series ahead of the 14CO2 traps.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Absorption and elimination of AA were rapid and nearly complete within 24 h after administration of single oral doses of either 150 or 40 mg/kg bw to C3H mice. Metabolism to 14CO2 was the major route of elimination, accounting for about 80% of the administered dose (92% of recovered radioactivity).
Details on distribution in tissues:
Approximately 1% or less of the dose remained in the tissues and carcass at the end of the experiment. Elimination of radioactivity from stomach tissue, plasma, liver and kidney was rapid, but it was somewhat slower from fat.
Details on excretion:
Urinary excretion accounted for about 3% of the dose, with most occurring during the first 24 h. Excretion in faeces accounted for about 1% of the dose. Only trace amounts of exhaled volatiles other than 14CO2 were detected.

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
Livers collected from orally dosed mice were analyzed by HPLC for AA and metabolites. Unchanged AA was not detected 1 h after oral administration; however, several metabolites that were more polar than AA were detected, including 3-hydroxypropionate and peak 1, the metabolite that was also the major urinary metabolite in rats. Neither AA nor its metabolites were detected at later times after oral administration.

Any other information on results incl. tables

The less than complete recovery of the administered doses is probably explained by the volatile nature of acrylic acid and its propensity to bind to materials such as plastic and glass, properties that may also be shared by some of the metabolites of acrylic acid.

Disposition of radioactivity in C3H mice after oral administration of [1 -14C]AA:

Dose

150 mg/kg bw

40 mg/kg bw

Exhaled 14CO2

80.0 ± 4.1

76.8 ± 2.8

Exhaled volatiles

0.1 ± 0.0

0.1 ± 0.0

Urine

3.4 ± 1.3

3.0 ± 1.4

Faeces

1.2 ± 1.2

1.2 ± 0.4

Cage wash

1.9 ± 2.2

0.5 ± 0.3

Tissues

0.1 ± 0.1

0.3 ± 0.0

Carcass

0.3 ± 0.1

0.8 ± 0.1

Total recovery

86.9 ± 6.1

82.5 ± 2.1

Applicant's summary and conclusion