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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: In this record studies on excretion of vinyl chloride upon inhalation exposure are combined. The studies have been published in peer-reviewed literature and are considered reliable for assessment.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Comparison of the fate of vinyl chloride following single and repeated exposure in rats.
Author:
Watanabe, P.G., Zempel, J.A. and Gehring, P.J.
Year:
1978
Bibliographic source:
Toxicol Appl Pharmacol 44:391-399
Reference Type:
publication
Title:
Fate of [14C]Vinyl Chloride following Inhalation Exposure in Rats
Author:
Watanabe, P.G., McGowan, G.R., Madrid, E.O. and Gehring, P.J.
Year:
1976
Bibliographic source:
Toxicol. Appl. Pharmacol. 37:49-59

Materials and methods

Objective of study:
excretion
Principles of method if other than guideline:
Clearance was measured after repeated (Watanabe et al, 1978) and single (Watanabe et al, 1976) exposure.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Radiolabelling:
yes
Remarks:
14C

Test animals

Species:
rat

Administration / exposure

Route of administration:
inhalation

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on excretion:
Watanabe et al, 1978:
The percentage of14C activity excreted by each route as well as the total milligram equivalents of VC recovered were essentially identical for the singly and repeatedly exposed groups. The majority of 14C activity eliminated was expired as VC per se.

While the binding of reactive metabolites of VC to hepatic macromolecules was enhanced following repeated exposure, no differences were observed in the activity of hepatic microsomal enzymes to the substrates aniline or p-nitroanisole in any of the treatment groups when compared to non-exposed control rats.
Percentage 14C activity eliminated within 72 hours following exposure to 5000 ppm vinyl chloride
Single exposure Repeated exposure
Expired
as VC 54.5+3.5 53.7+2.1
as CO2 8.0+1.4 9.6+1.6
Urine 27.1+2.1 25.7+1.4
Faeces 3.2+2.5 1.4+0.4
Carcass 7.3+2.5 9.7+1.6
and tissues

Watanabe et al, 1976:
dose (ppm) 10 ppm 1,000 ppm
(% of total 14C recovered)
expired VC 1.61 % 12.26 %
expired CO2 12.09 % 12.30 %
urine 67.97 % 56.29 %
faeces 4.45 % 4.21 %
carcass and tissue 13.84 % 14.48 %
pulmonary elimination: t1/2 = 20.4 min t1/2 = 22.4 min
urinary elimination:
initial phase t1/2 = 4.6 h t1/2 = 4.1 h
late phase variable variable
After 72 h highest concentration of 14C-activity in liver and skin (may be dose dependent).

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
Watanabe et al, 1976:
In urine three major metabolites (by HPLC) roughly independent of dose; two of the metabolites have been identified as N-acetyl-S-(2-hydroxyethyl)cysteine and thiodiglycolic acid.

Applicant's summary and conclusion