2-naphthol

Acute Toxicity: inhalation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Commission Directive of 25 April 1984

Deviations:

no

Test guideline 2

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

Test material

Test material information

Constituent 1

Reference substance name:

2-naphthol

EC Number:

205-182-7

EC Name:

2-naphthol

Cas Number:

135-19-3

Molecular formula:

C10H8O

IUPAC Name:

2-naphthol

Test material form:

solid

Test animals

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

Administration / exposure

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.

Results and discussion

Effect levels

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

Any other information on results incl. tables

See attached background documents

Applicant's summary and conclusion

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.