Naphthalene

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well documented study performed equivalent to OECD guideline.

Data source

Reference

Reference Type:

publication

Title:

Naphthalene Toxicity in CD-l Mice: General Toxicology and lmmunotoxicology

Author:

Shopp GM, White KL, Holsapple MP, Barnes DW, et al.

Year:

1984

Bibliographic source:

FUND. APPL. TOXICOL 4: 406-419 (1984)

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Acclimatisation period of test animals only 4 days instead of at least 5 days.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Naphthalene

EC Number:

202-049-5

EC Name:

Naphthalene

Cas Number:

91-20-3

Molecular formula:

C10H8

IUPAC Name:

naphthalene

Details on test material:

- Name of test material (as cited in study report): Naphthalene
- Source: Aldrich Chemical Company, Milwaukee, Wisconsin
- Substance type: organic, aromatic hydrocarbon
- Physical state: solid
- Analytical purity: pure, purity confirmed at 99.3% employing gas chromatography.
- Impurities (identity and concentrations): none reported
- Lot/batch No.: Lot No. EE09 1397

Test animals

Species:

mouse

Strain:

other: CD-1 ICR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Wilmington, Mass.
- Age at study initiation: 6 weeks
- Housing: in plastic cages with hardwood bedding (PWI Hardwood Sawdust, Lowville, N.Y.)
- Diet (e.g. ad libitum): Purina Rodent Chow No. 5001 (Ralston Purina Co., St. Louis, MO.) ad libitum
- Water (e.g. ad libitum): deionised water ad libitum
- Acclimation period: 4 days
- Fasting period: Mice were fasted for 18 hr prior to oral dosing, with food being returned 1 hr after dosing.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24°C
- Humidity (%): 40-60%.
- Photoperiod (hrs dark / hrs light): light-dark cycle was maintained on 12-hr intervals

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS:
A corn oil (Mazola Pure Corn Oil, Best Food, Englewood Cliffs, N.J., Lot No. 6-0729) suspension of naphthalene was prepared daily and stirred continuously during dosing

VEHICLE
- Concentration in vehicle: Concentrations of the corn oil-naphthalene suspension were prepared such that all doses could be delivered in a volume of I0 ml/kg body wt.
- Vehicle: Mazola Pure Corn Oil, Best Food, Englewood Cliffs, N.J.
- Lot/batch no. (if required): Lot No. 6-0729
- Purity: pure

Doses:

Five dose levels (200, 400, 600, 800, 1000 mgjkg) were employed to determine the acute oral LD50.

No. of animals per sex per dose:

8

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The mice were continuously observed for 1 hr after dosing, hourly for the next 4 hr, and then twice each day for the next 14 days.
- Necropsy of survivors performed: yes All mice that died during the observation period and those that survived the 14-day period were necropsied.

Statistics:

All mice that died during the observation period and those that survived the 14-day period were necropsied. The LDIO, LDSO, and LD90 were computed for each sex by the Log Probit Analysis as described by Finney (1971).

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

710 mg/kg bw

Based on:

test mat.

95% CL:

> 584 - < 827

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

533 mg/kg bw

Based on:

test mat.

95% CL:

> 397 - < 659

Mortality:

The majority of the naphthalene-associated deaths occurred within the first 5 hr after dosing, and all deaths occurred within the first 5 days.

Clinical signs:

other: With the exception of the low dose mice (200 mg/kg in males and 400 mg/kg in females) all mice developed ptosis with clear red secretions around the eye within 1 hr after dosing. Death followed depressed breathing and ataxia.

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Naphthalene did not induce haemolytic anaemia or cataract formation in CD 1 mice at the dosage levels employed. Male CD-1 mice (LD50 533 mg/kg body weight) are more susceptible to naphthalene than females (710 mg/kg body weight).

Executive summary:

An interesting finding in these studies was the lack of either naphthalene induced haemolytic anaemia or cataract formation in CD 1 mice at the dosage levels employed. Both these pathological lesions have been associated with human exposure to naphthalene.The acute toxicity data reported indicate that male CD-1 mice are more susceptible to naphthalene than females. Since little is known about the mechanisms associated with the acute toxicity of this compound, including whether the toxicity is associated with the parent compound or a metabolite, an understanding of the mechanisms responsible for the sex differences must await further investigation.

Naphthalene appears to be more toxic in mice when administered orally than parenterally.