Creosote oil, acenaphthene fraction

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study, limited documentation, acceptable for assessment of sub-lethal effects

Data source

Reference

Reference Type:

publication

Title:

Toxic effects of acute inhalation exposure to 1-methylnaphthalene and 2-methylnaphthalene in experimental animals

Author:

Korsak, Z.; Majcherek, W.; Rydzynski, K.

Year:

1998

Bibliographic source:

Inter. J. Occup. Med. Environ. Health 11, 335-342 (1998)

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

: male animals only, no post-exposure observation, lethal doses not technically attainable, additional testing (neurotoxic effects)

Principles of method if other than guideline:

The focus of the study was laid on test substance induced depression of CNS functions, thus allowing for the evaluation of sub-lethal effects.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1-methylnaphthalene

EC Number:

201-966-8

EC Name:

1-methylnaphthalene

Cas Number:

90-12-0

Molecular formula:

C11H10

IUPAC Name:

1-methylnaphthalene

Constituent 2

Reference substance name:

2-methylnaphthalene

EC Number:

202-078-3

EC Name:

2-methylnaphthalene

Cas Number:

91-57-6

Molecular formula:

C11H10

IUPAC Name:

2-methylnaphthalene

Constituent 3

Reference substance name:

202-078-2

IUPAC Name:

202-078-2

Details on test material:

- Name of test material (as cited in study report): 1-methylnaphthalene (1-MN)
- Source Riedel de Haen

- Name of test material (as cited in study report): 2-methylnaphthalene (2-MN)
- Source Fluka

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: IMP: DAK outbred stock
- Weight at study initiation: 250 - 300 g
- Housing: wire-mesh stainles steel cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 1 week, used within 4 weeks after arrival

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 25
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

clean air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: dynamic inhalation chamber
- Exposure chamber volume: 0.25 m3
- Air change 12 - 15x
- Method of holding animals in test chamber:
- Source and rate of air:
- Method of conditioning air:
- System of generating particulates/aerosols: Vapours were generated by heating the solvent in a washer to 85 °C.
- Method of particle size determination: none
- Treatment of exhaust air:
- Temperature, humidity, pressure in air chamber:

TEST ATMOSPHERE
- Brief description of analytical method used:
- Samples taken from breathing zone: yes/no

VEHICLE
- Composition of vehicle (if applicable):
- Concentration of test material in vehicle (if applicable):
- Justification of choice of vehicle:
- Lot/batch no. (if required):
- Purity:

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration:

Analytical verification of test atmosphere concentrations:

yes

Remarks:

GC FID, every 30 min

Duration of exposure:

4 h

Concentrations:

nominal: 150 - 500 mg/m3
1-MN - mean analytical concentrations: 152, 253, and 407 mg/m3 (the latter maximally attainable)
2-MN - mean analytical concentrations: 229, 325, and 522 mg/m3 (the latter maximally attainable)

No. of animals per sex per dose:

10 - 20

Control animals:

yes

Details on study design:

- Duration of observation period following administration: < 2 d
- Frequency of observations and weighing:
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, behaviour, pain tolerance

Statistics:

Kruskal-Wallis test for evaluating the decrease in the sensitivity to pain.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LC0

Effect level:

> 404 mg/m³ air (analytical)

Based on:

test mat.

Remarks:

1-MN

Exp. duration:

4 h

Remarks on result:

other: concentration maximally attainable

Effect levels 2

Sex:

male

Dose descriptor:

LC0

Effect level:

> 522 mg/m³ air (analytical)

Based on:

test mat.

Remarks:

2-MN

Exp. duration:

4 h

Remarks on result:

other: concentration maximally attainable

Effect levels 3

Sex:

male

Dose descriptor:

other: NOAEC (pain sensitivity)

Effect level:

152 mg/m³ air (analytical)

Based on:

test mat.

Remarks:

1-MN

Exp. duration:

4 h

Remarks on result:

other: Test for central-nervous effects

Effect levels 4

Sex:

male

Dose descriptor:

other: NOEC (pain sensitivity)

Effect level:

229 mg/m³ air (analytical)

Based on:

test mat.

Remarks:

2-MN

Exp. duration:

4 h

Remarks on result:

other: Test for central-nervous effects

Effect levels 5

Sex:

male

Dose descriptor:

other: NOAEC (balance reflexes)

Effect level:

404 mg/m³ air (analytical)

Based on:

test mat.

Remarks:

1-MN

Exp. duration:

4 h

Remarks on result:

other: Test for central-nervous effects

Effect levels 6

Sex:

male

Dose descriptor:

other: NOAEC (balance reflexes)

Effect level:

522 mg/m³ air (analytical)

Based on:

test mat.

Remarks:

2-MN

Exp. duration:

4 h

Remarks on result:

other: Test for central-nervous effects

Mortality:

none

Clinical signs:

other: no details

Body weight:

not applicable

Gross pathology:

not performed

Other findings:

Other observations:
1. Rotarod test (according to Kaplan and Murphy 1972):
No statistically significant influence on performance,
but 1/10 animals of the high-dose 2-MN group failed. (n = 10 per group)

2. Pain tolerance test (hot plate):
A statistically significant concentration-related influence on the paw-lick response was observed (see below).

Any other information on results incl. tables

Latency of the paw-lick response (hot-plate behaviour) in rats exposed to 1- or 2 -Methylnaphthalene, respectively

(Report, Table 3 and 4):

Group [mg/m^3]	Animal number	Latency of response [sec]	Mean decrease in pain sensitivity [%] #
1-Methylnaphthalene
Control	50	10.2 ±2.3	0
152	10	12.8 ±2.9	4.8
253	20	24.8 ±15.9 *	29
407	20	36.1 ±18.6 *	51.8
2- Methylnaphthalene
Control	20	10.5 ±2.6	0
229	10	13.9 ±3.3	6.8
352	10	25.7 ±6.3 *	30.7
525	20	33.3 ±19.9*	46.0

* Statistically significant difference from control: p =< 0.001

# Latency elongation to 60 sec over the control was taken as 100 % decrease in pain sensitivity

Applicant's summary and conclusion

Interpretation of results:

other: not classifiable

Executive summary:

1 -Methyl- and 2 -methylnaphthalene vapours were not lethal to rats exposed for 4 h to concentrations that were maximally attainable (407 and 522 mg/m3, respectively). They produced significant CNS depression shown by concentration-related decrease in the pain tolerance. The NOAECs for this sublethal effect were approx. 150 and 200 mg/m3 for 1 -MN and 2 -MN, respectively.

No significant but only slight impairment of the trained rotarod performance was observed with 1 of 10 failures in the high-dose 2 -MN group.