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Administrative data

Endpoint:
toxicity to reproduction
Remarks:
other: In vitro mechanistical study on oviductal function impairment
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
unsuitable test system

Data source

Reference
Reference Type:
publication
Title:
Pyridines in cigarette smoke inhibit hamster oviductal functioning in picomolar doses
Author:
Riveles K, Iv M, Arey J, Talbot P
Year:
2003
Bibliographic source:
Reprod Toxicol. 2003, 17(2):191-202; PMID: 12642152

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
From female golden hamsters, oviducts and ovaries were removed on day 5 of the estrous cycle and oocyte cumulus complexes (OCC) were recovered from the ovaries.

OOCYTE PICK UP ASSAY
The infundibula were dissected from the oviducts and placed into a perfusion chamber with the test item solution under a microscope. An OCC was placed at the base of the infundibulum and the time needed to traverse a defined length to the ostrium was measured.

CILIARY BEAT FREQUENCY ASSAY
Ciliary beat frequency was measured using hamster oviduct explants, which were placed in perfusion chambers containing the test item and being filmed with a video camera recording a defined number of frames per second. The number of frames per ciliary beat was measured and converted to beats per second.

INFUNDIBULAR MUSCLE CONTRACTION ASSAY
Muscle contraction of the infundibulum in a perfusion chamber with the test item was recorded using a microscope with attached video camera and measured on the monitor. This distance was then converted to actual distance by comparison to a micrometer placed under the microscope.
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2,2'-bipyridyl
EC Number:
206-674-4
EC Name:
2,2'-bipyridyl
Cas Number:
366-18-7
Molecular formula:
C10H8N2
IUPAC Name:
2,2'-bipyridyl
Details on test material:
- Name of test material (as cited in study report): 2,2-bipyridine

Test animals

Species:
hamster
Strain:
other: Golden hamster
Sex:
female

Administration / exposure

Route of administration:
other: in vitro immersion of oviducts into test item solution
Vehicle:
physiological saline
Remarks:
Earle's Balanced Salt Solution (EBSS)
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
The parts of the oviducts under examination were immersed in perfusion chambers containing EBSS and 2,2'-bipyridine.
Doses / concentrations
Remarks:
0.1 pM - 0.1 M
Basis:
nominal conc.
No. of animals per sex per dose:
6-10 measurements were performed per concentration
Control animals:
yes

Results and discussion

Results: P0 (first parental generation)

Details on results (P0)

Consecutive dosing in the range of 0.1 pM to 0.1 M was used to determine the concentration that caused effects in the three bioassays. For treatment with 2,2’-bipyridine, the LOAEL was determined to be 8.74 * 10^(-4) M in the oocyte pick-up assay, and 8.74 * 10(-2) M in the two other assays (Ciliary Beat Frequency and Infundibular Muscle Contraction Assay).

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

Table 1: LOAEL and efficacy of 2,2’-bipyridine on the oviduct measuring oocyte pick-up rate, ciliary beat frequency, and infundibular smooth muscle contraction rate

Effect measured

LOAEL [mol/L]

Inhibition at LOAEL [%]

oocyte pick-up rate

8.74 * 10-4

54.75

ciliary beat frequency

8.74 * 10-2

24.86

infundibular smooth muscle contraction rate

8.74 * 10-2

56.67

Applicant's summary and conclusion

Conclusions:
The test item 2,2'-bipyridine, when applied directly on the oviduct of female hamsters inhibits oviductal functioning. The LOAELs were determined to be 8.74 * 10^(-4) M (55% inhibition of oocyte transport), and 8.74 * 10^(-2) M (25% inhibition of ciliar movement and 57% inhibition of infundibular muscle contraction).
Executive summary:

The effect of 2,2’-bipyridine on oviductal function impairment was tested with 3 in vitro assays using female hamster oviducts. Measured parameters included oocyte pick-up rate, ciliary beat frequency and infundibular smooth muscle contraction rate.

Consecutive dosing in the range of 0.1 pM to 0.1 M was used to determine the concentration that caused effects in the three bioassays. For treatment with 2,2’-bipyridine, the LOAEL was determined to be 8.74 * 10 -4 M in the oocyte pick-up assay, and 8.74 * 10 -2 M in the two other assays (Ciliary Beat Frequency and Infundibular Muscle Contraction Assay).