1,8-naphthylenediamine

Endpoint summary

Description of key information

Ten male an ten female rats were exposed on 5 consecutive days for 6 hours per day nose/head only to an aerosol of 10, 75 or 394 mg 1,8-naphthylenediamine/m³ under dynamic conditions. The post-exposere time was 3 (intermediate section) or 17 days (endsection).
The animals were observed for mortality and clinical signs. In addition, clinical pathology of blood samples was performed. Organs and tissues were subjected to gross and histopathological investigation. 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: study based on OECDguideline 412 with a five days exposure

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)

Deviations:

yes

Remarks:

exposure 5 x 6 hours

Principles of method if other than guideline:

Ten male an ten female rats were exposed on 5 consecutive days for 6 hours per day nose/head only to an aerosol of 10, 75 or 394 mg 1,8-naphthylenediamine/m³ under dynamic conditions. The post-exposere time was 3 (intermediate section) or 17 days (endsection).
The animals were observed for mortality and clinical signs. In addition, clinical pathology of blood samples was performed. Organs and tissues were subjected to gross and histopathological investigation.

GLP compliance:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

other: ethanol/polyethyleneglycol

Duration of treatment / exposure:

6 hours each on 5 consecutive days

Frequency of treatment:

daily

Remarks:

Doses / Concentrations:
0, 10, 75 or 394 mg/m³
Basis:
analytical conc.

No. of animals per sex per dose:

10 male and 10 female rats/dose

Control animals:

yes, concurrent vehicle

Dose descriptor:

NOAEC

Effect level:

75 mg/m³ air (analytical)

Based on:

test mat.

Sex:

male/female

Critical effects observed:

not specified

The exposition to the test substance was tolerated by all animals without mortality. Animals exposed to 394 mg/m³ 1,8-naphtylene- diamine revealed a decreased motility and a reduction in body weight gain.

A concentration dependant decrease of the rectal temperature was evident at a concentration of 10 mg/m³.

A decrease of the leucocyte number and an increase of the bilirubin concentration in plasma was found on animals exposed to 394 mg/m³.

The relative spleen weight was reduced in male rats at 394 mg testsubstance/m³.

All effects were reversible within the post-observation period.

Executive summary:

Ten male an ten female rats were exposed on 5 consecutive days for 6 hours per day nose/head only to an aerosol of 10, 75 or 394 mg 1,8-naphthylenediamine/m³ under dynamic conditions. The post-exposere time was 3 (intermediate section) or 17 days (endsection).

The animals were observed for mortality and clinical signs. In addition, clinical pathology of blood samples was performed. Organs and tissues were subjected to gross and histopathological investigation.

The exposition to the test substance was tolerated by all animals without mortality. Animals exposed to 394 mg/m³ 1,8-naphtylene- diamine revealed a decreased motility and a reduction in body weight gain. A concentration dependant decrease of the rectal temperature was evident at a concentration of 10 mg/m³. A decrease of the leucocyte number and an increase of the bilirubin concentration in plasma was found on animals exposed to 394 mg/m³. The relative spleen weight was reduced in male rats at 394 mg testsubstance/m³. All effects were reversible within the post-observation period.

Animals exposed to 394 mg 1,8-naphylenediamin revealed effects induced by the test material. Based on the hypothermic effect on animals exposed to 10 mg 1,8-naphthylendiamine a NOEL could not be established. The NOAEC is regarded to be 10 mg 1,8 -naphthylenediamine/m³.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEC

75 mg/m³

Study duration:

subacute

Species:

rat

Quality of whole database:

scientifically acceptable and well documented - but only 5 days exposure

Repeated dose toxicity: inhalation - local effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: study based on OECDguideline 412 with a five days exposure

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)

Deviations:

yes

Remarks:

exposure 5 x 6 hours

Principles of method if other than guideline:

Ten male an ten female rats were exposed on 5 consecutive days for 6 hours per day nose/head only to an aerosol of 10, 75 or 394 mg 1,8-naphthylenediamine/m³ under dynamic conditions. The post-exposere time was 3 (intermediate section) or 17 days (endsection).
The animals were observed for mortality and clinical signs. In addition, clinical pathology of blood samples was performed. Organs and tissues were subjected to gross and histopathological investigation.

GLP compliance:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

other: ethanol/polyethyleneglycol

Duration of treatment / exposure:

6 hours each on 5 consecutive days

Frequency of treatment:

daily

Remarks:

Doses / Concentrations:
0, 10, 75 or 394 mg/m³
Basis:
analytical conc.

No. of animals per sex per dose:

10 male and 10 female rats/dose

Control animals:

yes, concurrent vehicle

Dose descriptor:

NOAEC

Effect level:

75 mg/m³ air (analytical)

Based on:

test mat.

Sex:

male/female

Critical effects observed:

not specified

The exposition to the test substance was tolerated by all animals without mortality. Animals exposed to 394 mg/m³ 1,8-naphtylene- diamine revealed a decreased motility and a reduction in body weight gain.

A concentration dependant decrease of the rectal temperature was evident at a concentration of 10 mg/m³.

A decrease of the leucocyte number and an increase of the bilirubin concentration in plasma was found on animals exposed to 394 mg/m³.

The relative spleen weight was reduced in male rats at 394 mg testsubstance/m³.

All effects were reversible within the post-observation period.

Executive summary:

Ten male an ten female rats were exposed on 5 consecutive days for 6 hours per day nose/head only to an aerosol of 10, 75 or 394 mg 1,8-naphthylenediamine/m³ under dynamic conditions. The post-exposere time was 3 (intermediate section) or 17 days (endsection).

The animals were observed for mortality and clinical signs. In addition, clinical pathology of blood samples was performed. Organs and tissues were subjected to gross and histopathological investigation.

The exposition to the test substance was tolerated by all animals without mortality. Animals exposed to 394 mg/m³ 1,8-naphtylene- diamine revealed a decreased motility and a reduction in body weight gain. A concentration dependant decrease of the rectal temperature was evident at a concentration of 10 mg/m³. A decrease of the leucocyte number and an increase of the bilirubin concentration in plasma was found on animals exposed to 394 mg/m³. The relative spleen weight was reduced in male rats at 394 mg testsubstance/m³. All effects were reversible within the post-observation period.

Animals exposed to 394 mg 1,8-naphylenediamin revealed effects induced by the test material. Based on the hypothermic effect on animals exposed to 10 mg 1,8-naphthylendiamine a NOEL could not be established. The NOAEC is regarded to be 10 mg 1,8 -naphthylenediamine/m³.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

375 mg/m³

Study duration:

subacute

Species:

rat

Quality of whole database:

scientifically acceptable and well documented - but only 5 days exposure

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The exposition to the test substance was tolerated by all animals without mortality. Animals exposed to 394 mg/m³ 1,8-naphtylene- diamine revealed a decreased motility and a reduction in body weight gain.

A concentration dependant decrease of the rectal temperature was evident at a concentration of 10 mg/m³.

A decrease of the leucocyte number and an increase of the bilirubin concentration in plasma was found on animals exposed to 394 mg/m³. The relative spleen weight was reduced in male rats at 394 mg test substance/m³. All effects were reversible within the post-observation period.

The systemic NOAEC was regarded to be 75 mg/m³. No local adverse effect was obseved at 394 mg/m³ (highest applied dose).

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
key study used

Justification for classification or non-classification

The systemic NOAEC was regarded to be 75 mg/m³ due to the effects on blood parameters (leucocyte count, bilirubin), decreased motility, reduction in body weight gain and the decrease of spleen weight at 394 mg/m³. No local adverse effect was observed at 394 mg/m³ (highest applied dose).

As the exposure duration in this subacute study was only 5 days, for specific target organ toxicity- repeated, insufficient data are available (data lacking) for classification.