Sodium acrylate

Basic toxicokinetics

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:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

1995

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Disposition and metabolism of Acrylic acid (AA) in C3H mice after single cutaneous administration.

GLP compliance:

yes

Test material

Test material information

Constituent 1

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.)

Specific details on test material used for the study:

- 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:

dermal

Vehicle:

acetone

Details on exposure:

TEST SITE
- Area of exposure: 1.0 X 1.0 cm
- Type of wrap if used: nonocclusive dose containment devices constructed from Stomahesive and cemented to the skin with Skin-Bond
- Time intervals for shavings or clipplings: prior to application


REMOVAL OF TEST SUBSTANCE
- Washing (if done): at the end of experiment to remove the unabsorbed portion of the dose


TEST MATERIAL
- concentration (if solution): 1 mL test AA/100 mL acetone


VEHICLE
- Amount(s) applied (volume or weight with unit): 0.95 and 3.8 mL/kg bw, respectively

Duration and frequency of treatment / exposure:

72 hrs

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

10 mg/kg bw/day (actual dose received)

Doses / concentrations 2

Dose / conc.:

40 mg/kg bw/day (actual dose received)

No. of animals per sex per dose / concentration:

15

Control animals:

no

Details on study design:

- Dose selection rationale: The cutaneous dose levels were selected based on previous work on the cutaneous toxicity of AA in several strains of mice (DePass et al. 1984, Tegeris et al. 1988).

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. In addition to the in-line volatile organics trap, the dose-containment device was modified by cementing activated charcoal-impregnated filter paper sheets to the top of the frame in order to trap the volatile fraction of the applied dose at the dosing site.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

After cutaneous administration of single doses (40 or 10 mg/kg bw) to C3H mice, the processes of AA absorption and elimination were rapid and nearly complete within 8 h. Evaporation from the dosing site accounted for the largest fraction of the applied dose, although total recovery of the dose was variable. After 40 mg/kg bw, 11.4 ± 1.7% (mean t ± SD, n= 5) of the dose was absorbed (sum of cumulative proportions exhaled as 14CO2 or excreted in urine or faeces and the proportions found in dosing site skin, tissues, and carcass at 72 h), and after 10 mg/kg bw, 12.4 ± 3.3% was absorbed. Metabolism to 14CO2 was the major route of elimination, accounting for 83.5 ± 8.4% and 77.7 ± 10.4% of the absorbed dose after the high and low dose, respectively. Elimination via other routes was minor.

Details on distribution in tissues:

At the end of the experiment, 0.2-1.5% of the dose was found in the dosing site skin, and about 1% was found in tissues and carcass. Exhalation of volatile organic compounds other than 14CO2 was not quantified separately but was presumed to be negligible based on the results from orally dosed animals. Elimination of radioactivity from the dosing site skin, plasma, liver, and kidney was rapid. The concentration of radioactivity found in fat at 72 h was greater than that found at 1 or 8 h.

Metabolite characterisation studies

Metabolites identified:

no

Details on metabolites:

Neither AA nor its metabolites were detected in livers from mice at any time after cutaneous administration of 40 mg/kg bw.

Any other information on results incl. tables

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

	Dose
	40 mg/kg bw	10 mg/kg bw
14CO2	9.6 ± 2.2	9.3 ± 1.2
Volatilized dose	49.9 ± 12.6	70.9 ± 9.6
Urine	0.4 ± 0.1	0.3 ± 0.1
Faeces	0.2 ± 0.1	0.4 ± 0.1
Cage wash	0.2 ± 0.1	0.2 ± 0.1
Tissues	0.0 ± 0.0	0.2 ± 0.1
Carcass	0.8 ± 0.8	0.5 ± 0.1
Dosing-site skin	0.2 ± 0.1	1.5 ± 2.3
Skin rinse	0.2 ± 0.1	0.6 ± 0.3
Total recovery	61.5 ± 14.0	84.0 ± 10.5

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.