Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: dermal
Type of information:
experimental study
Adequacy of study:
other information
Study period:
12 Nov 1979 - 13 Feb 1981
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: The test substance was one ingredient of a formulation.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 411 (Subchronic Dermal Toxicity: 90-Day Study)
Deviations:
yes
Remarks:
only one dose was tested, application site was left uncovered, no ophthamological examination conducted
GLP compliance:
no
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Medicated Lotion, 13824-32
- Analytical purity: no data
- Composition of test material, percentage of components: contains 0.3% Propylparaben

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Blue Spruce Farms, Altamont, NY, USA
- Weight at study initiation: 176 - 200 g (males), 151 - 175 g (females)
- Housing: Animals were housed singly in stainless steel cages with wire floors.
- Diet: Teklad Mouse/Rat Pellets, ad libitum
- Water: Licket, ad libitum
- Acclimation period: 10 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 1
- Humidity (%): 50 ± 5
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
From: 12 Nov 1979
To: 13 Feb 1980

Administration / exposure

Type of coverage:
open
Vehicle:
other: the test substance is an ingredient of Medicated Lotion, 13824-32
Details on exposure:
TEST SITE
- % coverage: 10 - 15
- Time intervals for shavings: once weekly
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
12.4 mg/kg bw/d
Basis:
nominal per unit body weight
No. of animals per sex per dose:
10
Control animals:
yes, concurrent no treatment

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: once daily

DERMAL IRRITATION (if dermal study): Yes

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

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

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: during weeks 7 and 13
- Anaesthetic used for blood collection: Yes, diethyl ether
- Animals fasted: Yes, overnight
- How many animals: all animals

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: during weeks 7 and 13
- Animals fasted: Yes, overnight
- How many animals: all animals

URINALYSIS: Yes
- Time schedule for collection of urine: during weeks 7 and 13
- Animals fasted: Yes, overnight

NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes (adrenals, brain, esophagus, eye, heart, hind leg muscle and sciatic nerve, kidneys, large and small intestines, liver, lungs, ovaries, pancreas, treated skin site, spleen, stomach, testes, thyroid, trachea, mesenteric lymph nodes, urinary bladder, uterus, sternum, any unusual lesions), including organ weights of adrenals, brain, heart, kidneys, liver, lungs, spleen, testes, uterus

HISTOPATHOLOGY: Yes (adrenals, heart, brain, kidneys liver, lungs, pancreas, treated skin site, spleen, testes, uterus, bone marrow from sternum, any unusual lesions)

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
but non-adverse
Dermal irritation:
effects observed, treatment-related
Description (incidence and severity):
but non-adverse
Mortality:
mortality observed, treatment-related
Description (incidence):
but non-adverse
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
but non-adverse
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
but non-adverse
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
but non-adverse
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
but non-adverse
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
histopathological changes of the treated skin site
Histopathological findings: neoplastic:
not specified
Details on results:
CLINICAL SIGNS AND MORTALITY
No mortality occurred during the study period. Sporadic minimal to moderate skin irritation at the treated skin sites and a brown discoloration of the fur immediately around the treated skin site was noted. Additionally, in a number of animals, significant thinning of the fur around the treatment site was observed. Hyperactivity just before and immediately after dosing was noted in a few animals and some problems regarding equilibrium were observed.

BODY WEIGHT AND WEIGHT GAIN
Lower body weight and a significant decrease in body weight gain was observed for males. The body weight and body weight gain for females was consistent with the values of the concurrent control group.

HAEMATOLOGY
The determined blood parameters are in the range of the values of the untreated control group, with exception of the mean corpuscular volume (MCV), which was slight but significantly elevated in females after 7 and 13 weeks.

CLINICAL CHEMISTRY
Most of the tested serum chemistry values were comparable to that of the untreated control. After 7 weeks, a decreased glucose value in females was noticed, which was in the range of the untreated control after 13 weeks. At the end of the study period, significant increases were observed in male urea nitrogen values and in female alkaline phosphate values.

URINALYSIS
No treatment related changes were noticed in the urinalysis after 7 and 13 weeks.

ORGAN WEIGHTS
In males, significant decreases in absolute brain, heart, liver, spleen and adrenal weights and significantly increased relative brain, lung and testes weights were observed. In females, absolute liver and relative heart and liver weights were significantly increased and absolute and relative spleen weight were significantly decreased.

GROSS PATHOLOGY
No treatment related abnormalities were noticed at necropsy.

HISTOPATHOLOGY: NON-NEOPLASTIC
Significant histopathological changes were limited to the treated skin site.

Effect levels

Dose descriptor:
NOAEL
Effect level:
12.4 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: corresponding to 0.3% of the test substance in the formulation

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion