1,8-naphthylenediamine

Endpoint summary

Description of key information

Valid studies for acute oral, dermal and inhalation toxicity are available

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Five male and five female Wistar rats received a single dose of 200, 356, 632, 1124, or 2000 mg/kg bw (male rats) and 200, 356, 474, 632, or 2000 mg/kg bw (female rats) of 1,8-naphtylendiamine per gavage. The animals were observed for mortality, body weights and clinical signs through day 14. A gross necropsy was performed on animals which died during the observation period or were sacrificed at the end of the 14 days observation period.

GLP compliance:

yes

Test type:

standard acute method

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

other: 1,2-propandiol

Doses:

male rats: 200, 356, 632, 1124, or 2000 mg/kg bw (
female rats: 200, 356, 474, 632, or 2000 mg/kg bw

No. of animals per sex per dose:

5 mael and 5 female rats/dose

Control animals:

no

Sex:

female

Dose descriptor:

LD50

Effect level:

591 mg/kg bw

Based on:

test mat.

Sex:

male

Dose descriptor:

LD50

Effect level:

>= 1 124 - <= 2 000 mg/kg bw

Based on:

test mat.

For male rats a LD50 in the range between 1124 and 2000 mg/kg bw was found, and for female rats a LD50 of 591 mg/kg bw was determined

As signs of intoxication in all dose groups sedation was observed. Some animals in the higher dose groups revealed, a poor general condition, polyurie and cyanosis. Body weight development was not affected, but one female rats had a body weight reduction in the 2nd week.

In the dose group of 474 to 2000 mg/kg bw, the stomach was filled with discolored liquid, stomach and intestines were stained.

some animals revealed a urinary bladder fileed with brownish-red liquid.. Two male animals killed at the end of the observation period had pale kidneys. All other animals had no pathological findings.

Executive summary:

Five male and five female Wistar rats received a single dose of 200, 356, 632, 1124, or 2000 mg/kg bw (male rats) and 200, 356, 474, 632, or 2000 mg/kg bw (female rats) of 1,8-naphtylendiamine per gavage. The animals were observed for mortality, body weights and clinical signs through day 14. A gross necropsy was performed on animals which died during the observation period or were sacrificed at the end of the 14 days observation period.

For male rats a LD50 in the range between 1124 and 2000 mg/kg bw was found, and for female rats a LD50 of 591 mg/kg bw was determined

As signs of intoxication in all dose groups sedation was observed. Some animals in the higher dose groups revealed, a poor general condition, polyurie and cyanosis. Body weight development was not affected, but one female rats had a body weight reduction in the 2nd week.

In the dose group of 474 to 2000 mg/kg bw, the stomach was filled with discolored liquid, stomach and intestines were stained.

some animals revealed a urinary bladder fileed with brownish-red liquid.. Two male animals killed at the end of the observation period had pale kidneys. All other animals had no pathological findings.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

591 mg/kg bw

Quality of whole database:

The materials/methods and results are described in detail and are sufficient for evaluation.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Four groups of 5 male and 5 female Wistar rats were nose/head-only exposed to an aerosol concentration of 1,8-naphthylendiamine at an analytical concentration of 0, 156, 413 or 877 mg/m³ (highest technical feasible concentration) for 4 hours. The animals were observed for mortality, weight and clinical signs through day 14. A gross necropsy was performed.

GLP compliance:

yes

Test type:

standard acute method

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

other: acetone-polyethylenglycol 400 in air

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

0. 156, 413 or 877 mg 1,8-naphthylendiamine/m³ air

No. of animals per sex per dose:

5 male and 5 female rats/concentration

Control animals:

yes

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 877 mg/m³ air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: highest technical feasible concentration

An exposition up to 877 mg/m³ 1,8-naphtylenediamine (highest technical feasible concentration) was tolerated without mortality. All animals exposed to 413 and 877 mg/m³ and revealed at the first exposition day a reduced motility and a bloody nose, additional one rat exposed to 413 mg/m³ a reduced respiration rate. All rats had no clinical symptoms at the first post-observation day. At the 3rd post-observation day in all rats exposed to 413 mg/m³ and in female rats exposed to 877 mg/m³ a reduction of weight gain was observed.

Executive summary:

Four groups of 5 male and 5 female Wistar rats were nose/head-only exposed to an aerosol concentration of 1,8-naphthylendiamine at an analytical concentration of 0, 156, 413 or 877 mg/m³ (highest technical feasible concentration) for 4 hours. The animals were

observed for mortality, weight and clinical signs through day 14. A gross necropsy was performed.

An exposition up to 877 mg/m³ 1,8-naphtylenediamine (highest technical feasible concentration) was tolerated without mortality. All animals exposed to 413 and 877 mg/m³ and revealed at the first exposition day a reduced motility and a bloody nose, additional one rat exposed to 413 mg/m³ a reduced respiration rate. All rats had no clinical symptoms at the first post-observation day. At the 3rd post-observation day in all rats exposed to 413 mg/m³ and in female rats exposed to 877 mg/m³ a reduction of weight gain was observed. Therefore the LC50 is > 877 mg/kg bw for male and female rats

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

877 mg/m³ air

Quality of whole database:

The materials/methods and results are described in detail and are sufficient for evaluation.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

5 male and 5 female Wistar rats were treated occlusively with a single application of 2000 mg/kg bw of 1,8-naphthylendiamine. The animals were observed for mortality, body weights and clinical signs through day 14. Gross pathological examinations were done on all animals sacrificed at the end of study. Necropsy records were prepared for all animals.

GLP compliance:

yes

Test type:

standard acute method

Species:

rat

Strain:

Wistar

Sex:

male/female

Type of coverage:

occlusive

Vehicle:

other: 1,2-propandiole

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 male and 5 female rats were applied a dose of 2000 mg/kg bw

Control animals:

no

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

No signs of systemic poisoning were observed and no skin changes were seen. Two male rats and one female rats showed a slight decrease in body weight during the 1st and 2nd study week, respectively. No deaths occured. None of the animals sacrificed at the end of the 14-day observation period showed any noticable gross pathological findings.

Executive summary:

Five male and five female Wistar rats were treated occlusively with a single application of 2000 mg/kg bw of 1,8-naphthylendiamine. The animals were observed for mortality, body weights and clinical signs through day 14. Gross pathological examinations were done on all animals sacrificed at the end of study. Necropsy records were prepared for all animals.

No death occured (LD50 > 2000 mg/kg bw). No signs of systemic poisoning were observed and no skin changes were seen. Two male rats and one female rats showed a slight decrease in body weight during the 1st and 2nd study week, respectively. None of the animals sacrificed at the end of the 14-day observation period showed any noticable gross pathological findings.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

The materials/methods and results are described in detail and are sufficient for evaluation.

Additional information

Five male and five female Wistar rats received a single dose of 200, 356, 632, 1124, or 2000 mg/kg bw (male rats) and 200, 356, 474, 632, or 2000 mg/kg bw (female rats) of 1,8-naphtylendiamine per gavage. For male rats a LD50 in the range between 1124 and 2000 mg/kg bw was found, and for female rats a LD50 of 591 mg/kg bw was determined.

Four groups of 5 male and 5 female Wistar rats were nose/head-only exposed to an aerosol concentration of 1,8-naphthylendiamine at an analytical concentration of 0, 156, 413 or 877 mg/m³ (highest technical feasible concentration) for 4 hours. An exposition up to 877 mg/m³ 1,8-naphtylenediamine (highest technical feasible concentration) was tolerated without mortality.

Five male and five female Wistar rats were treated occlusively with a single application of 2000 mg/kg bw of 1,8-naphthylendiamine.

No death occured (LD50 > 2000 mg/kg bw).

Justification for selection of acute toxicity – oral endpoint
key study used

Justification for selection of acute toxicity – inhalation endpoint
key study used

Justification for selection of acute toxicity – dermal endpoint
key study used

Justification for classification or non-classification

Due to the results of the acute oral toxicity study (LD50 = 591 mg/kg bw for female rats) a classification as Xn, R22 (GHS: Acute tox. 4, H302) is justified.

For acute dermal and inhalation toxicity a classification is not justifed based on reliable experimental studies.