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Toxicological information

Repeated dose toxicity: dermal

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Administrative data

Endpoint:
sub-chronic toxicity: dermal
Type of 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: source substance and target substance are sharing very similar structural formula
Justification for type of information:
source substance and target substance are sharing very similar structural formula
Cross-reference
Reason / purpose:
read-across source
Reference
Endpoint:
sub-chronic toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Qualifier:
according to
Guideline:
other: Food and Drug Administration (FDA) Good Laboratory Practice Regulations for Nonclinical Studies (GLP Guidelines)
GLP compliance:
yes
Species:
mouse
Strain:
B6C3F1
Sex:
male/female
Type of coverage:
not specified
Vehicle:
ethanol
Remarks:
Doses / Concentrations:
0, 200, 400, 600, 800 and 1000mg/kglday
Basis:
nominal per unit area
No. of animals per sex per dose:
There were 10 mice ofeach sex in each dose group
Observations and examinations performed and frequency:
Body weight determinatiousand clinical observations were recorded weekly. Mice were bled for hematology determinations at study termination, were necropsied,organ weights recorded, and tissues processed for microscopic examination.
Other examinations:
Hematologyparameters were not affected by camphor treatment.Absolute lung weights were reduced in female mice at the 1000 mglkg dose. All necropsy findings were considered incidental and consistent with gross lesions fi:equently occurring in B6C3F1 mice ofthis age.
The only treatment-relatedmicroscopic change was increasedepidermal hyperplasia seen in the skin from the application site ofall 1000mglkg mice
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
not specified
Haematological findings:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Details on results:
The only treatment-relatedmicroscopic change was increasedepidermal hyperplasia seen in the skin from the application site ofall 1000mglkg mice. The epithelial hyperplasia seen in this subchronic study was qualitatively similar to that observed in the l4-day dermal study. Continuation of treatment through 90 days did not appear to cause a significant progressionofthe skin reaction. Several animals at the 800, 600, and 400 dose levels also exhibited epithelial hyperplasia. Based on a finding ofhyperplasia in a control female mouse,the incidenceof this condition in the 400 mglkg group was considered within normal limits. Thus, the no-effect level for epithelial hyperplasiawas considered to be400 mg/kg.
Dose descriptor:
other: NEL
Effect level:
400 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: epithelial hyperplasia
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
Critical effects observed:
not specified

Data source

Reference
Reference Type:
review article or handbook
Title:
Unnamed
Year:
1998

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Food and Drug Administration (FDA) Good Laboratory Practice Regulations for Nonclinical Studies (GLP Guidelines)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female

Administration / exposure

Type of coverage:
not specified
Vehicle:
ethanol
Doses / concentrations
Remarks:
Doses / Concentrations:
0 (vehicle), 16,32,64, 125 and 250 mg/kglday
Basis:
nominal per unit area
No. of animals per sex per dose:
There were 10 rats ofeach sex in the Core Study dose groups

Examinations

Observations and examinations performed and frequency:
Body weights and clinical observations were recorded weekly.

Results and discussion

Results of examinations

Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
kidney weight increases, lung weight decreases
Details on results:
Hematology parameters were not adversely affected by camphor treatment. Decreases in blood urea nitrogen and alanine aminotransferase appeared to be related to camphor treatment and were evident early (on Days 4 and 23). However, these indices were unchanged at Day 93 and, thus, were considered not to have any toxicological significance.Relative lung weights were reduced in female rats at doses of64 and 250 mg/kg and relative kidney weights were increased in males at 64 mg/kg. All other findings at necropsy were considered incidental and consistent with those frequently seen in Fischer 344 rats ofthis age.

Effect levels

Dose descriptor:
NOAEL
Effect level:
250 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion