Propyl 4-hydroxybenzoate

Repeated dose toxicity: dermal

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

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

Test material information

Constituent 1

Reference substance name:

Propyl 4-hydroxybenzoate

EC Number:

202-307-7

EC Name:

Propyl 4-hydroxybenzoate

Cas Number:

94-13-3

Molecular formula:

C10H12O3

IUPAC Name:

propyl 4-hydroxybenzoate

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 or test system 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