Registration Dossier

Administrative data

Endpoint:
neurotoxicity
Remarks:
acute
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The methodology used by the authors is not fully described and most elements of the study design and of te experimental conditions are unknwon. Hence, this study should be considered as not assignable due to insufficient documentation, a Klimisch 4.e study.

Data source

Reference
Reference Type:
publication
Title:
The effect of industrial solvents on adrenergic transmitter mechanisms
Author:
Holmberg B. and Malmfors T.
Year:
1974
Bibliographic source:
Wenner-Gren Cent. Ist. Symp. Ser., 22, 191-200.

Materials and methods

Principles of method if other than guideline:
The effects of benzyl chloride on the adrenergic transmission was studied by using both in vitro and in vivo systems. The authors studied in both cases the mechanical response of mouse vas deferens innervated or denervated.
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
α-chlorotoluene
EC Number:
202-853-6
EC Name:
α-chlorotoluene
Cas Number:
100-44-7
Molecular formula:
C7H7Cl
IUPAC Name:
(chloromethyl)benzene
Constituent 2
Reference substance name:
Chloromethylbenzene
IUPAC Name:
Chloromethylbenzene
Details on test material:
- Name of test material (as cited in study report): benzyl chloride
No further data

Test animals

Species:
mouse
Strain:
NMRI
Sex:
not specified

Administration / exposure

Route of administration:
intravenous
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
one single exposure by i.v. injection
Frequency of treatment:
once
Doses / concentrations
Remarks:
Doses / Concentrations:
3, 10, 100 ppm
Basis:
no data
No. of animals per sex per dose:
No data
Control animals:
yes

Results and discussion

Applicant's summary and conclusion

Conclusions:
In the test conditions, the authors report that benzyl chloride may affect the adrenergic transmission probably on both the nerve and the effector side. However, the practical significance of these results remain to be confirmed in further in vivo experiments. Thus further testing would be requested to conclude about the neurotoxic potential of benzyl chloride.
Executive summary:

The neurotoxic effects of benzyl chloride (CAS n° 100 -44 -7 ) on the adrenergic transmission was studied by using both in vitro and in vivo systems. The authors studied in both cases the mechanical response of NMRI mice vas deferens innervated or denervated. A screening step wes conducted in vitro to establish benzyl chloride effects on the adrenergic transmission. This experiment' results has triggered further testing in vivo. Only in vivo results will be discussed here. Furthermore, in order to elucidate te sensitivity to benzyl chloride of the effector cells involved in the adrenergic transmission, the adrenergic nerves of mice were removed by 6-OH-DA injected the day before to the animals and the mechanical response of vas deferens was elicited by exogenous NA in complement or not to various concentrations of benzyl chloride, namely 3, 10 or 100 ppm.

Hence, in the test conditions, benzyl chloride had a marked potentiating effect after nerve stimulation. However, the responses observed were not consistent with the in vitro experiment. Indeed, there was a slight potetianting effect in the innervated mouse vas deferens, while 100 ppm of benzyl chloride rather had a slight opposite effect in the denervated mouse vas deferens. This indicated the inhibiting effect on the NA uptake of benzyl chloride might have some importance in the innervated mouse vas deferens, while the absence of post-synaptic supersensitivity in the denervated mouse vas deferens makes the potentiating effect after electric stimulation more difficult to explain. However, the authors explained that in unpublished results, 100 ppm of benzyl chloride in vitro had a degenerative effect on the smooth muscle cells and thus leading to an irrversible damage of the smooth muscle cells at that concentration. They assume then that the potentiating effect of benzyl chloride at electric stimulationmust therefore be explained by an excessive release of the transmitter by the nerve impulses.

Finally, in the test conditions, the authors report that benzyl chloride may affect the adrenergic transmission probably on both the nerve and the effector side. However, the practical significance of these results remain to be confirmed in further in vivo experiments. Thus further testing would be requested to conclude about the neurotoxic potential of benzyl chloride.

The methodology used by the authors is not fully described and most elements of the study design and of te experimental conditions are unknwon. Hence, this study should be considered as not assignable due to insufficient documentation, a Klimisch 4.e study.