2-naphthol

Endpoint summary

Description of key information

The acute toxicity of the test substance 2-naphthol via the oral route was evaluated during a study performed according to the OECD Testing Guideline 401 (Acute Oral Toxicity).  The study was GLP compliant.

 

The fixed dose method was used.  The following doses were investigated and administered by gavage.

 

1250 mg/kg bw: concentration in sesame oil: 25%, administration volume: 5 ml/kg b.w.
1600 mg/kg bw: concentration in sesame oil: 25%, administration volume: 6 and 4 ml/kg b.w.
2000 mg/kg bw: concentration in sesame oil: 25%, administration volume: 8 ml/kg b.w.
2500 mg/kg bw: concentration in sesame oil: 25%, administration volume: 10 ml/kg b.w.

 

Following exposure to the test substance, animals were observed for 14 days.  Lethality occured until day 3 after administration.  The following clinical signs were observed at the day of administration: decreased spontaneous activity, squatting position, prone/lateral position, irregular breathing, respiratory rales, narrowed palpebral fissure and bristled fur.  In higher doses (as from 1600 mg/kw/bw) dizziness, tonic-clonic seizures and decreased position reflexes were observed.  From day 1 after administration withdrawn flanks, blood clored incrusted muzzles and diarrhoea were observed.  For one make animal in the 2500 mg/kg/bw group the position- and paw pinch-reflex was eliminated.  For a female animal in the 2500 mg/kg/bw group no increase of body weight could be determined after 7 days.  At the end of the test period, this animal considerably exceeded its initial weight.  The development of body weight for the other animals was not affected.  The macroscopic examination of the died male and female animals revealed the following characteristics: blood vessels of the gastrointestinal tract considerably injected - stomach and small intestine filled with substance remains - stomach inflated - clotted blood in small intestines - urinary bladder fillded with brownish-gloomy liquid.  The animals killed at the end of the follow-up period were free of macroscopic visible changes.

 

Based on LD50 values of 1340 mg/kw/bw in female rats and 1300 mg/kg/bw in males rats, 2-naphthol was classified as harmful according to the CLP regulation.

 

The acute toxicity of the test substance 2-naphthol via the inhalation route was evaluated during a study performed according to the OECD Testing Guideline 403 (Acute Inhalation Toxicity).  The study was GLP compliant.

 

Groups of 5 male and female Wistar rats were exposed for 4 hours to concentrations of 0.9, 1.94, 2.50, 5.06 mg/L (air) of 2-naphthol. The substance was aerosoled at 50% in polyethylene glycol 400 / ethanol (1:1).

Analysis were conducted during exposure to confirm the actual concentrations the animals were exposed to.

At the end of exposure, animals were observed for 14 days. Bodyweight and clinical signs were recorded. At the end of the observation period, surviving animals were necropsied.

All the animals exposed to the highest concentration of test substance in air were found dead by the end of the observation period. At 2.50 mg/L (air), 9/10 animals died as a result of the exposure. 1/10 animals exposed to 1.94 mg/L (air) of test substance for 4 hours was found dead. All the animals exposed to 0.90 mg/L (air) survived until the end of the observation period.

The animals showed irregular respiration, sonorous rales, panting, gasping, sneezing, narrowed palpebral fissures, stilted, uncoordinated and ataxic gait, ataxia, trembling, decreased spontaneous activity, sunken flanks, squatting posture, prone position, straddling hind limbs, forward crawling, ruffled and bristling coat, blood-coloured encrusted noses, blood coloured nasal discharge, stupor, sedation, reduced or absent pawreflex to pinching, reduced or no placing reflex, delayed or no corneal reflex, corneal opacity and diarrhea.

Body weight development was impaired during the first week. At the end of the study, all surviving animals had surpassed their initial weights.

At necropsy, changes were observed in the lungs of animals.

The 4h-LC50 was determined to be 2.20 mg/L (air) based on the deaths observed during the study. Since this value is between 1.0 and 5.0 mg/L (air), 2-naphthol meets the criteria for classification as Acute Tox. 4; H332 according to Regulation (EC) No.1272/2008.

 

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

Study period:

13.08.1986 - 10.09.1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

12.05.1981

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

age of the animals at the test beginning:
male rats: 7 weeks
female rats: 8 weeks

Route of administration:

oral: gavage

Vehicle:

other: Oleum Sesami, Ph. Eur. III

Details on oral exposure:

1250 mg/kg bw: concentration in sesame oil: 25%, administration volume: 5 ml/kg b.w.
1600 mg/kg bw: concentration in sesame oil: 25%, administration volume: 6 and 4 ml/kg b.w.
2000 mg/kg bw: concentration in sesame oil: 25%, administration volume: 8 ml/kg b.w.
2500 mg/kg bw: concentration in sesame oil: 25%, administration volume: 10 ml/kg b.w.

Doses:

1250 mg/kg bw, 1600 mg/kg bw, 2000 mg/kg bw, 2500 mg/kg bw

No. of animals per sex per dose:

10 (5 male, 5 female)

Control animals:

not specified

Details on study design:

observation period after administration: 14 d

Statistics:

LD50, 95% CL and the equation of the probit straight line were determined via probit analysis from different lethality rates.

Preliminary study:

In preliminary tests the doses to be further investigated were found to be 1600 - 2500 mg/kg b.w.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

1 300 mg/kg bw

Based on:

test mat.

95% CL:

>= 426 - <= 1 710

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

1 340 mg/kg bw

Based on:

test mat.

95% CL:

>= 469 - <= 1 750

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 320 mg/kg bw

Based on:

test mat.

95% CL:

>= 728 - <= 1 560

Mortality:

Lethality occured until day 3 after administration.

Clinical signs:

other: The following clinical signs have been observed at the day of administration: decreased spontaneous activity, squatting position, prone / lateral position, irregular breathing, respiratory rales, narrowed palpebral fissure and bristled fur. In higher dose

Gross pathology:

The macroscopic examination of the died male and female animals revealed the following cahracteristics:
- blood vessels of the gastrointestinal tract considerably injected
- stomach and small intestine filled with substance remains
- stomach inflated
- clotted blood in small intestine
- urinary bladder filled with brownish-gloomy liquid

Other findings:

The killed animals at the end of the follow-up period were free of macroskopic visible changes.

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

former R 22

Conclusions:

Based on LD50 values of 1340 mg/kg bw in female rats and 1300 mg/kg bw in male rats 2-naphthol was classified as harmful according to the criteria of EC Directive 83/467/CEE.
Based on these values the test item beta-naphthol has to be classified as harmful according to CLP-regulation.

Executive summary:

In an assay according to OECD TG 401 on the acute oral toxicity of beta-naphthol the following values for the LD₅₀ were determined:

For male and female animals: 1320 mg/kg bw (wistar rats)

For male animals: 1300 mg/kg bw (wistar rats)

For female animals: 1340 mg/kg bw (wistar rats)

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 300 mg/kg bw

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

Study period:

1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Version / remarks:

Commission Directive of 25 April 1984

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

Version 1981.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

traditional method

Limit test:

no

Species:

rat

Strain:

Wistar

Remarks:

Hoe: WISKf (SPF71)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG, Kastengrund, SPF Breeding Colony
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 10 weeks
- Weight at study initiation: Females: 176 - 206 g. Males: 177 to 217 g.
- Fasting period before study: not specified
- Housing: Groups of 5 animals in Makrolon cages (Type 4) on soft wood granulates.
- Diet: Altromin 1324 rat diet ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24°C
- Humidity (%): 30 - 70%
- Air changes (per hr): air-conditioned rooms, air changes not specified.
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Remarks:

The test substance was aerosoled in polyethylene glycol 400 / ethanol

Mass median aerodynamic diameter (MMAD):

1.657 µm

Geometric standard deviation (GSD):

2.03

Remark on MMAD/GSD:

MMAD was determined for all test concentrations. See attached background information.

Details on inhalation exposure:

The exposure camber consisted of a stainless-steel and glass cylinder with a volume of 60L, standing in a vent pipe with a volume of ca. 4 m3. The chambers were tested to confirm they yielded a uniform distribution of aerosols in the breathing zones of the animals.
After passing through an oil separation filter and an absolute filter, air was pumped at a pressure of 4 bar into a special nozzle with a welded-in supply tube for the test substance. The air supply at the nozzle was maintained at 800 L/h by means of an air calibrated rotameter.
The test substance could not be dispersed either in its original state or after micronizing, and was therefore aerolised in polyethylene glycol 400 / ethanol at 50%. It was injected into a nozzle at a constant speed by means of a continuous infusion apparature and then directly in the inhalation chamber (primary aerosol). This application method was chosen, as higher concentrations could be achieved when compared with secondary aerosol technique.
In order to ensure a higher atmospheric humidity, air was passed via a porous stone at a rate of 100 L/h through a 1,000 mL vacuum filter flask filled with water. The moisturized air was then conducted straight into the exposure chamber.
A suction device at the bottom of the exposure chamber drew off the aerosol at a rate of 1,100 L/h through a washing flask filled with water, a cotton-wool filter, a Buehler filter and a calcium chloride flask.
The difference in rate between the introduction of air at 800 L/h through the nozzle and its extraction at 1,100 L/h is necessary to maintain the kinetic energy of the aerosol particles and to ensure a laminar flow of the aerosol from the top to the bottom of the exposure chamber. Additional air enters via the animal cages, but causes no significant dilution of the aerosol.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

0.90, 1.94, 2.50 and 5.06 mg/L (air)

No. of animals per sex per dose:

5 animals/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Behaviour check were carried out twice daily (once daily during week-end). Animals were weighted on Days 1, 8 and 15.
- Necropsy of survivors performed: yes

Statistics:

The LC50, 95% limits of confidence and equation of the probit lines were established on the basis of the mortality rates by probit analysis.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

2.2 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

10/10 exposed to 5.06 mg/L (air) of test substance for 4 hours died as a result of the exposure.
9/10 animals exposed to 2.50 mg/L (air) of test substance for 4 hours died as a result of the exposure.
1/10 animals exposed to 1.94 mg/L (air) of test substance for 4 hours died as a result of the exposure.
0/10 animals exposed to 0.90 mg/L (air) of test substance for 4 hours died as a result of the exposure.

Clinical signs:

other:

Body weight:

Body weight development was impaired during the first week. At the end of the study, all surviving animals had surpassed their initial weights.

Gross pathology:

Autopsy of the animals found dead revealed the following changes:
- Lungs discoloured red, dark red and black
- Lungs patchy (red or dark-red)
- Foam or blood coloured liquid escaped after dissection of lungs

See attached background documents

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LC50 of the test item in rats following a 4-hour exposure via the inhalation route was determined to be 2.20 mg/L (air). The test item meets the criteria for classification as Acute Tox. 4; H332 according to Regulation (EC) No.1272/2008 since the value is between 1.0 and 5.0 mg/L.

Executive summary:

The acute toxicity: inhalation of the test substance was determined in accordance with the OECD Guideline for Testing of Chemicals 403. The study was GLP-compliant.

Groups of 5 male and female Wistar rats were exposed for 4 hours to concentrations of 0.9, 1.94, 2.50, 5.06 mg/L (air) of 2-naphthol. The substance was aerosoled at 50% in polyethylene glycol 400 / ethanol (1:1).

Analysis were conducted during exposure to confirm the actual concentrations the animals were exposed to.

At the end of exposure, animals were observed for 14 days. Bodyweight and clinical signs were recorded. At the end of the observation period, surviving animals were necropsied.

All the animals exposed to the highest concentration of test substance in air were found dead by the end of the observation period. At 2.50 mg/L (air), 9/10 animals died as a result of the exposure. 1/10 animals exposed to 1.94 mg/L (air) of test substance for 4 hours was found dead. All the animals exposed to 0.90 mg/L (air) survived until the end of the observation period.

The animals showed irregular respiration, sonorous rales, panting, gasping, sneezing, narrowed palpebral fissures, stilted, uncoordinated and ataxic gait, ataxia, trembling, decreased spontaneous activity, sunken flanks, squatting posture, prone position, straddling hind limbs, forward crawling, ruffled and bristling coat, blood-coloured encrusted noses, blood coloured nasal discharge, stupor, sedation, reduced or absent pawreflex to pinching, reduced or no placing reflex, delayed or no corneal reflex, corneal opacity and diarrhea.

Body weight development was impaired during the first week. At the end of the study, all surviving animals had surpassed their initial weights.

At necropsy, changes were observed in the lungs of animals.

The 4h-LC50 was determined to be 2.20 mg/L (air) based on the deaths observed during the study. Since this value is between 1.0 and 5.0 mg/L (air), 2-naphthol meets the criteria for classification as Acute Tox. 4; H332 according to Regulation (EC) No.1272/2008.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

2.2 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because inhalation of the substance is likely

Justification for classification or non-classification

Following an acute oral toxicity study in rats, it was determined the 2-naphthol had an LD50 value of 1300 mg/kg/bw and is classified as harmful according to Regulation EC No. 1272/2008.

 

Following an acute inhalation toxicity study in rats, it was determined that 2-naphthol had an LC50 value of 2.2 mg/m3 and meets the criteria for classification as Acute tox. 4 according to Regulation EC No. 1272/2008.