N,N'-diphenylguanidine monohydrochloride

Neurotoxicity

Description of key information

It was confirmed that the test item in doses of 5 mg/kg influences the activity of the cerebral cortex (outer layer of the brain). Thus, the test item has a stimulating effect - the response in the animals accelerates, then at one moment breaks down and there is no response any more. With doses at up to 1 mg/kg, no toxic effects on the nervous system were observed.

The dosage of 5 mg/kg turned out to be the lowest dose at which effects were observed. However, based on the conditions of this study these effects cannot be judged as adverse.

Key value for chemical safety assessment

Effect on neurotoxicity: via oral route

Link to relevant study records

Reference

Endpoint:

neurotoxicity: chronic oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1970

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Principles of method if other than guideline:

Using a method of conditioned reflexes in a chronic experiment the nature and extend of the effects of the test substance on the central nervous system of the tested animals was determined.

GLP compliance:

no

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

White male rats were tested.
Weight: 120 - 140 g
The rats were devided in 6 groups - 3 groups were treated with the source substance and 3 groups were treated with the target substance. Additionally, 2 groups were included as control groups.

Route of administration:

oral: unspecified

Vehicle:

water

Details on exposure:

The test substances were were administered in equal volumes of destilled water at a rate of 1 mL per 100 g weight. The control group received the same amount distilled water as the treatment groups.

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

Treatment: 4 months

Frequency of treatment:

6 times a week

Dose / conc.:

0.025 mg/kg bw/day (nominal)

Dose / conc.:

0.5 mg/kg bw/day (nominal)

Dose / conc.:

5 mg/kg bw/day (nominal)

No. of animals per sex per dose:

5 males per treatment group

Control animals:

yes, concurrent vehicle

Details on study design:

The source substance was tested in 3 treatments - 0.05, 1 and 10 mg/kg.

Key result

Dose descriptor:

NOAEL

Effect level:

0.5 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Key result

Dose descriptor:

LOAEL

Effect level:

5 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Key result

Critical effects observed:

no

In the control groups the mean signal number was 43 with latent period of 0.92 +/- 0.06 seconds.

In treatments 0.05 and 1 mg/kg bw of the source substanmce, no signifficant differences with the control group were observed. In treatment group 10 mg/kg bw an effect was observed - the latent period was 1.9 +- 0.19 seconds, which was double the period of the control aminals. It is considered that at a dose level of 10 mg/kg bw the substance has an inhibitory effect of the central nervous system of white rates.

In treatments groups 0.025 and 0.5 mg/kg bw with the substance, no signifficant difference was observed with the control animals. Mean number of signals was 42 - 43. The latent period also did not differ with the one for the control animals. In the treatment of 5 mg/kg bw target substance an effect was observed. The latent period was decreased - 0.74 +- 0.06 seconds, compared to the control. The reaction period increased at 3.6 ,compared to 1.0 for the control animals. There was also some acceleration of the development of the reflex, but the reaction was strengthened even later than in the animals in the control group.

Differences in the strength of the motor reaction in experimental and control animals were not detected.

The reversability was fast and the normal reflexes in the animals were restored.

It was confirmed that the target test substance in doses of 5 mg/kg bw influences the activity of the cerebral cortex (outer layer of the brain). Thus, the test item has a stimulation effect - the responce in the animals accelerates, then at one moment breaks down and there is no responce more. If the dose in up to 1 mg/kg bw, no toxic effects on the nervous system will be observed.

The dosage of 5 mg/kg bw turned out to be the lowest dose at which effects were observed.

Conclusions:

It was confirmed that the target test substance in doses of 5 mg/kg bw influences the activity of the cerebral cortex (outer layer of the brain). Thus, the test item has a stimulation effect - the response in the animals accelerates, then at one moment breaks down and there is no response any more. If the dose in up to 1 mg/kg bw, no toxic effects on the nervous system will be observed.
The dosage of 5 mg/kg bw turned out to be the lowest dose at which effects were observed.

Executive summary:

A study on white male rats was performed to determined the effects of the target test substance on the central nervous system. Six groups of 5 male rats each were treated. 3 concentrations of the target test substance - 0.025, 0.5 and 5 mg/kg bw, and 3 concentrations of the source substance - 0.05, 1 and 10 mg/kg bw were tested. Parallel ran 2 control groups. The tested substances were applied orally 6 times a week for 4 months. Using a method of conditioned reflexes in a chronic experiment the nature and extend of the effects of the test substance on the central nervous system of the tested animals was determined. The reflexes of the treated animals towards a bell sound were observed. The latent period and reflex signals were noted. Treated animals with 0.05 and 1 mg/kg bw source substance and with 0.025 and 0.5 mg/kg bw target substance showed no significant differences to the control groups. At the highest tested concentrations for both substances - 5 mg/kg bw for the target and 10 mg/kg bw for the source, inhibitory effects on the activity of the cerebral cortex were observed. The NOAEL for the target substance was determined to be 0.5 mg/kg bw, while the LOAEL was 5 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

0.5 mg/kg bw/day

Study duration:

chronic

Species:

rat

Effect on neurotoxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Effect on neurotoxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

A study on white male rats was performed to determined the effects of the target test substance on the central nervous system. Six groups of 5 male rats each were treated. 3 concentrations of the target test substance - 0.025, 0.5 and 5 mg/kg, and 3 concentrations of the source substance - 0.05, 1 and 10 mg/kg were tested. Parallel ran 2 control groups. The tested substances were applied orally 6 times a week for 4 months. Usind a method of conditioned reflexes in a chronic experiment the nature and extend of the effects of the test substance on the central nervous system of the tested animals was determined. The reflexes of the treated animals towards a bell sound were observed. The latent period and reflex signals were noted. Treated animals with 0.05 and 1 mg/kg source substance and with 0.025 and 0.5 mg/kg target substance showed no significant differences to the control groups. At the highest tested concentrations for both substances - 5 mgkg for the target and 10 mg/kg for the source, inhibitory effects on the activity of the cerebral cortex were observed. The NOEL for the test item was determined to be 0.5 mg/kg, while the LOEL was 5 mg/kg.