Registration Dossier

Toxicological information

Acute Toxicity: other routes

Currently viewing:

Administrative data

Endpoint:
acute toxicity: other routes
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: Acceptable, well-documented publication which meets basic scientific principles

Data source

Reference
Reference Type:
publication
Title:
Alkylnaphthalene. XI. Pulmonary Toxicity of Naphthalene, 2-Methylnaphthalene, and Isopropylnaphthalenes in Mice
Author:
Honda T, Kiyozumi M, and Kojima S
Year:
1990
Bibliographic source:
Chem Pharm Bull 38, 3130-3135
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
Experimental lung model in mice: Comparative study with naphthalene derivatives, based on the expression of pulmonary epithelial necrosis in mouse. 
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2-isopropylnaphthalene (2-IPN)
- 2-IPN from Tokyo Kasai Chemical Co., Tokyo, Japan
- puriefied by column chromatography

Test animals

Species:
mouse
Strain:
other: ddY
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Inoue Breeding Laboratory, Kumamoto, Japan
- Age at study initiation: no data
- Weight at study initiation: 18 - 23 g
- Fasting period before study: no data
- Housing: in cages on hard wood bedding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 3 days

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
olive oil
Doses:
1000mg/kg bw and 3000 mg/kg bw (single dose)
No. of animals per sex per dose:
3 to 5 animals per dose level

Results and discussion

Mortality:
none
Clinical signs:
not relevant (see under "Remarks on results...")
Body weight:
no data
Gross pathology:
see under "Remarks on results..."
Other findings:
see under "Remarks on results..."

Any other information on results incl. tables

No lung damage/necrosis was observed up to 3000 mg/kg (highest dose tested) at 24 h post treatment with and without a GSH depletor, diethyl maleate (DEM), although the GSH level was significantly reduced by the treatment. No or only mild changes in GSH were evident up to ca. 600 mg/kg. No influence on lipid peroxidation was observed.

 

On contrast, naphthalene and methylnaphthalene exhibited massive pathological disorders above approx. 200 and 400 mg/kg, respectively.

 

Note: Administration of naphthalene and 2-methylnaphthalene caused a considerable depletion of pulmonary GSH within 6 h, while 2-isopropyl and 2,6-diisopropyl naphthalene at doses up to 3000 mg/kg bw caused only a slight GSH loss. But also despite pretreatment with DEM associated with a decrease in pulmonary GSH, no lung damage was produced by either test substance.

Applicant's summary and conclusion

Conclusions:
These results suggest that the pulmonary toxicity depends markedly on the number of carbon of the substituent and the damage tends to decrease with an increase in the carbon number and number of alkyl substituents.