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Toxicological information

Specific investigations: other studies

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Administrative data

Endpoint:
biochemical or cellular interactions
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Influence of sodium salts of saturated medium chain length (C6, C9, C10 and C12) dicarboxylic acids on the uterine horn of rat in vitro
Author:
Mingrone G, Mancinelli R and Metro D
Year:
1988
Bibliographic source:
Quart. J. Exp. Physiol. 73, 153-162

Materials and methods

Principles of method if other than guideline:
The in vitro action of C6, C9, C10 and C12 dicarboxylic acid sodium salts  on the mechanical and extracellular electrical activity on the uterine  
horn of rats was studied
Type of method:
in vitro

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
35 female Wistar rats in natural oestrus and weighing 250-300 g 

Administration / exposure

Details on exposure:
The in vitro action of C6, C9, C10 and C12 dicarboxylic acid sodium salts  on the mechanical and extracellular electrical activity on the uterine  horn 
of rats was studied:
- Rats: 35 female Wistar rats in natural oestrus and weighing 250-300 g  were anesthetized. After a mid-line incision, both uterine horns were  
quickly removed and placed in a bath of Krebs solution (37 °C, pH 7.4).
- For measuring only mechanical events, a vertical arrangement was used.  The ovarian end of a uterine horn was ligated and tied to an isometric  
force transducer connected to a chart recorder; the cervical end of the  horn was connected to a hook in the bath.
- For measuring mechanical and electrical events, a similar arrangement  in horizontal position was used. The extracellular electrical activity  was 
recorded by means of a glass capillary pressure electrode. Mechanical  and electrical activities were simultaneously recorded.
- Concentrations of acetylcholine, oxytocin and prostaglandins evoking  maximal isometrical contraction were checked for each uterine horn.
- Dicarboxylic salt effect was measured as the percentage reduction in  amplitude and in frequency of the spontaneous activity and as the  
percentage reduction for only the amplitude of the evoked contraction.

Results and discussion

Any other information on results incl. tables

- Spontaneous activity of the uterine muscle in rats was inhibited in  vitro by the sodium salts of dicarboxylic acids.
- Total abolition of mechanical events was observed at a dodecanedioic  acid concentration of 0.024 M.
- The intensity of this effect decreased in the order C12 > C10 > C9 > C6  dicarboxylic acid: 

0.024 M - 0.032 M - 0.040 M - 0.064 M.
- A 50 % decrease in amplitude and frequency of spontneous contraction  waves was observed at 

0.009 M / 0.016 M / 0.033 M - 0.038 M for C12 / C10  / C9 / C6 dicarboxylic acid.
- Activity of the uterine muscle induced by administration of  acetylcholine, oxytocin or prostaglandins (PGF2a) was antagonized by  

these salts. The order of reactivity was also C12 > C10 > C9 > C6.
- In general, inhibition of induced contractions required higher dicarboxylic acid concentrations than inhibition of spontaneous  

contractions.
- The results suggested that the inhibitory effects on smooth muscle could be due to a cellular membrane hyperpolarization.

Applicant's summary and conclusion

Conclusions:
In vitro effects were noted at very high concentration of concentration of 24 mmolar.
Executive summary:

The influence of the sodium salt of some dicarboxylic acids (adipic acid, C6; azelaic acid, C9; sebacic acid, C10; dodecandioic acid, C12) on both spontaneous and evoked activity of uterine horn of rats has been studied in vitro. Spontaneous activity of uterine muscle was inhibited by dicarboxylic salts (DS) causing the total abolition of mechanical events at concentrations of 64 x 10(-3) M-C6, 40 x 10(-3) M-C9, 32 x 10(-3) M-C10 and 24 x 10(-3) M-C12. Dicarboxylic salts antagonized the maximal isometric contraction of the uterine horn induced by administration of acetylcholine, oxytocin or prostaglandins (PGF2 alpha). The amount of antagonism was dependent upon the concentration of DS used. Dicarboxylic salt showed an aspecific inhibitory effect on the uterine horn which progressively increased with their chain length (C12 greater than C10 greater than C9 greater than C6). The results suggested that the inhibitory effects of DS on smooth muscle could be due to a cellular membrane hyperpolarization.