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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study submitted in the ELINCS notification dossier.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EU Method B.26 (Sub-Chronic Oral Toxicity Test: Repeated Dose 90-Day Oral Toxicity Study in Rodents)
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2-(phenylmethoxy)naphthalene
EC Number:
405-490-3
EC Name:
2-(phenylmethoxy)naphthalene
Cas Number:
613-62-7
Molecular formula:
C17H14O
IUPAC Name:
2-(benzyloxy)naphthalene

Test animals

Species:
rat
Strain:
Wistar

Administration / exposure

Route of administration:
oral: feed
Vehicle:
acetone
Duration of treatment / exposure:
90 days
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
200 ppm
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
1000 ppm
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
5000 ppm
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
20000 ppm
Basis:
nominal in diet
No. of animals per sex per dose:
20 in the control and in the highest concentration.
10 in the remaining groups
Control animals:
yes, concurrent no treatment

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Decrease of body weight on certain weeks in the group 5 animals and in females of group 4. Not reversible in males of the group 5 at the end of the recovery period (duration unknown). Same observation for the body weight gain.
Food consumption and compound intake (if feeding study):
no effects observed
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
On week 13, in males: reduced red cell count (group 4) and prothrombin time (group 5). Females: reduced red cell count (group 4 and 5), decrease of hemoglobin (group 4), of hematocrit (groups 4 and 5), and white cells count (all treated groups), higher MC
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
Dose dependent increase of gamma-GT activity, statistically significant in the group 5. This effect is reversible.
Urinalysis findings:
no effects observed
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
In the males of the group 5: Increase of the relative liver, testis and kidney weights. In the females: Increase of the relative liver weight (group 4 and 5), of the spleen (group 4 and 5) and of the brain (group 4). The effects are reversible in the fem
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed

Effect levels

Dose descriptor:
NOAEL
Effect level:
5 000 ppm
Sex:
male/female
Basis for effect level:
other: corresponding to 427 mg/kg/day for males and 513 mg/kg/day for females.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The effects that were considered to be linked to the substance are the reduction of the body weight and of the body weight gain in the group 5, and also the increase of the gamma-GT activity. This effect is related to the increase of the relative liver weight without histolopathological effect. In the other groups, the abnormalities are slight and in the normal range of variation of this strain of rats.
Executive summary:

A sub-chronic study has been performed in the rat with the substance administered in the diet at concentrations of 200; 1000; 5000 and 20000 ppm. The study was in accordance with the guideline B26.

A recovery period was included in the study.

The NOAEL is 5000 ppm corresponding to 427 mg/kg/day and 513 mg/kg/day in males and females, respectively. The effects observed were a reduction of the body weight and of the body weight gain, and an increased activity of the gamma-GT linked to an increase of the relative liver weight. No histopathological effects was observed.