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Toxicological information

Neurotoxicity

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Administrative data

Endpoint:
neurotoxicity
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Documentation insufficient for assessment No data on purity, on number of animals per group, no quantitative data

Data source

Reference
Reference Type:
publication
Title:
Dithiocarbamate fungicides decrease histochelical reactivity of cholinesterases in the gut wall of the rat.
Author:
Savolainen K and Hervonen H.
Year:
1985
Bibliographic source:
Arch. Toxicol. suppl. 8: 272-276

Materials and methods

GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Other name : Ethylenethiourea (ETU)
ETU was obtained from Fluka AG, Swizerland

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 160-220g
- Fasting period before study: no data
- Housing: plastic cages on pine cutter chips
- Diet (e.g. ad libitum): Standard pellet diet (Hankkija, Finland), ad libitum
- Water (e.g. ad libitum): not precised, ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
other: saline solution
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
4 days
Frequency of treatment:
once a day
Doses / concentrations
Remarks:
Doses / Concentrations:
200 mg/kg/day
Basis:
nominal conc.
Control animals:
yes, concurrent vehicle

Examinations

Observations and clinical examinations performed and frequency:
no data
Specific biochemical examinations:
Sections of ileum were removed after the 4-day treatment. Their reactivity to acetylcholinesterase and non specific cholinesterase was semi-quantitatively histochemically studied (0 to +++).
Neurobehavioural examinations performed and frequency:
no data
Positive control:
no data
Statistics:
no data

Results and discussion

Results of examinations

Description (incidence and severity):
Migrated information from 'Further observations for developmental neurotoxicity study'

Details on results (for developmental neurotoxicity):Possible damage to the cholinergic innervation of the gut of the rat. (migrated information)
Details on results:
Compared with the controls (+++) there was a decrease in the reactivity to both acetylcholinesterase and non-specific cholinesterase (++).

Any other information on results incl. tables

Table : Summary of the effects of ETU on the histochemical enzyme activity for acetylcholinesterase (AchE) and for non-specific cholinesterase (nsChE) in the rat intestine.

The reaction intensities are estimated by eye in the coded specimens using a scale from 0 (no reaction product) to 3+ (maximal reaction). Each estimation represent the mean of 3 samples.

Treatment

Cholinesterase reactivity

AChE

nsChE

Control/W

+++

+++

ETU

++

++

Control/W indicates saline controls, Control/GCW indicates control receiving 1% gum acacia in saline. ETU were given as a solution in saline.

Applicant's summary and conclusion

Executive summary:

Male Wistar rats were given ETU in saline i.p.200 mg/kg daily for 4 d, and the control rats received a corresponding volumeof saline i.p. After decapitation, pieces of ileum were taken, and the enzyme histochemical reactivity for the acetylcholinesterase (AChE) and for the non­specific cholinesterase (nsChE) in the ilea of the treated and control animals wasstudied. The reaction intensities in the samples were estimated by eye using a scale from 0 (no reaction product) to 3 + (maximal reaction). DSF was used as an internal standard. Controls showed the maximal reaction for the AChE and for the nsChE. ETU showed consistent decrease in the reactivity for the AChE (+ +) and for the nsChE (+ +). The decrease by DSF of the reactions for both the AChE (+) as well as for the nsChE(+) was even more pronounced indicating a possible nerve damage to the cholinergicinnervation of rat intestine.