Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Cited as secondary source with limited data.

Data source

Reference
Reference Type:
secondary source
Title:
2-Week dermal dose range finding study of diphenyl ether, beta-naphthyl methyl ether, p-methylanisol and 2-phenoxyethyl isobutyrate in rats.
Author:
C.Atkinson, M.Mulhern, F.Macnaughtan and C.J.Perry.
Year:
1994
Bibliographic source:
Report to RIFM; Location 23238.

Materials and methods

Principles of method if other than guideline:
A 2-week range-finding study, performing daily dermal applications for 6 hours per day for 14 days in Sprague-Dawley rats.
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): p-methylanisole

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: approx. 9 weeks
- Weight at study initiation: 225-235g (male), 156-179g (female)
- Housing: 1 per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 15 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+/- 2
- Humidity (%): 55 +/- 10
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
other: Diethylphtalate
Details on exposure:
TEST SITE
- Area of exposure: 4 cm2
- Type of wrap if used: gauze with silver foil back + semiocclusive dressing secured with tape
- Time intervals for shavings or clipplings: once weekly


REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed with diethylphtalate
- Time after start of exposure: immediately after removal of dressing and before next test substance application.


TEST MATERIAL
The neat test material or the test material in diethyl phthalate (DEP) was applied at a volume of 1 and 2 ml/kg, respectively.
Tested as a 50% solution in DEP at 66, 190, and 700 mg/kg bw/d.
Tested as the neat material at 1000 mg/kg bw/d.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
6 hours per day for 14 days
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 66, 190, 700, 1000 mg/kg bw/d
Basis:
nominal per unit body weight
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
other: Control group for the dose group receiving neat test material was treated with 2 ml/kg bw destilled water
Positive control:
no

Examinations

Observations and examinations performed and frequency:
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: no data

DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: no data

BODY WEIGHT: Yes
- Time schedule for examinations: no data

FOOD CONSUMPTION: Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data

WATER CONSUMPTION: Yes
- Time schedule for examinations: no data

HAEMATOLOGY: Yes
- Time schedule for collection of blood: No data
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- Parameters: No data

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: No data
- Animals fasted: No data
- Parameters: No data

URINALYSIS: Yes
- Time schedule for collection of urine: No data
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters: No data
Sacrifice and pathology:
GROSS PATHOLOGY: Yes + organ weights (no further data)
HISTOPATHOLOGY: Yes (no further data)

Results and discussion

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

1000 mg/kg bw/d: With the neat test material, all rats were sacrificed on day 9 due to severe irritation.

700, 190, 66 mg/kg bw/d: Besides irritation at the test site, no findings were observed that were considered to be related to treatment with the test material.

Applicant's summary and conclusion