Heptanal

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Study period:

From 1 December 1980 To 29 December 1980

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: 3b: Significant methodological deficiences

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)

Deviations:

no

Remarks:

One dose was tested instead of three. Time exposure was of 14 days instead of 21/28 days. No haematology and no clinical biochemistry determination on blood were performed.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Heptanal

EC Number:

203-898-4

EC Name:

Heptanal

Cas Number:

111-71-7

Molecular formula:

C7H14O

IUPAC Name:

heptanal

Details on test material:

- Name of test material (as cited in study report): C-191
- Substance type: C7 aldehyde
- Physical state: colorless liquid
- Impurities (identity and concentrations): no data
- Analytical purity: no data
- Purity test date: no data
- Lot/batch No.: C-191
- Expiration date of the lot/batch: no data
- Storage condition of test material: Room temperature (stored under nitrogen blanket)

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: dutchland Laboratory Animals Denver, Pennsylvania.
- Age at study initiation: young adults
- Weight at study initiation: 2.1 to 3.2 kg (Males); 2.3 to 3.2 kg (Females)
- Fasting period before study:
- Housing: individual
- Diet : ad libitum, Purina Rabbit chow.
- Water : ad libitum.
- Acclimation period: 21 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 to 21
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod : 12 hrs dark / 12 hrs light


IN-LIFE DATES: From: 1 December 1980 To: 29 December 1980

Administration / exposure

Type of coverage:

open

Vehicle:

other: mineral oil

Details on exposure:

TEST SITE
- Area of exposure: dorsal and lateral surfaces
- % coverage: about 10 % of the total body surface
- Time intervals for shavings or clipplings: Prior to the first dose, the hair was clipped and it was reclipped as necessary during the dosing period.


REMOVAL OF TEST SUBSTANCE
- Washing (if done):
- Time after start of exposure:


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg/kg/day
- Concentration (if solution):
- Constant volume or concentration used: yes/no
- For solids, paste formed: yes/no


VEHICLE
- Justification for use and choice of vehicle (if other than water):
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:


USE OF RESTRAINERS FOR PREVENTING INGESTION: yes/no

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

two consecutive weeks

Frequency of treatment:

5 days per week

Doses / concentrations

Remarks:

Doses / Concentrations:
500 mg/kg/day
Basis:
nominal per unit body weight

No. of animals per sex per dose:

5

The skin of half the animals (3 males and 2 females per group) was abraded and the skin of half the animals (2 males, 3 females) remained intact.

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: no data

Positive control:

None

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

DETAILED CLINICAL OBSERVATIONS: No data

DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: observations for signs of dermal irritation were made prior to the first dose and daily thereafter.


BODY WEIGHT: Yes
- Time schedule for examinations: Body weights were recorded pretest and weekly during the study.


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


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 data


WATER CONSUMPTION: No data


OPHTHALMOSCOPIC EXAMINATION: No data


HAEMATOLOGY: No data

CLINICAL CHEMISTRY: No data

URINALYSIS: No data

NEUROBEHAVIOURAL EXAMINATION: No data

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Other examinations:

None

Statistics:

No statistics were performed.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Dermal irritation:

effects observed, treatment-related

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

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:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

CLINICAL SIGNS AND MORTALITY
No mortality was observed during the course of the study.

BODY WEIGHT AND WEIGHT GAIN
Most animals exhibited sight weight losses (0.1 to 0.4 kg) after one and/or two weeks of study. Animals held for a two week recovery period exhibited weight gains during this interval.

DERMAL OBSERVATIONS
Most animal exhibited slight or moderate erythema with minimal edema and no necrosis or eschar formation during the first week of study. Necrosis and eschar formation, atnia, fissuring, desquamation and exfoliation occurred subsequently (during the second week of study) in all animals. One animal exhibited hair loss. Dermal responses subsided in animals held for recovery.

GROSS PATHOLOGY
Morphologic abnormalities of the treated skin were observed more frequently in rabbits from treated group than in animals from control. Discolorations of the gastric mucosa were observed in several of the treated animals. Other morphologic findings observed grossly occured sporadically in the treated and/or control animals. They did not appear to be related to the administration of the test compounds.

MICROSCOPIC OBSERVATIONS
Treatment-related tissue reactions occurred in abraded as well as non-abraded sites where the compound was applied. Epidermal necrosis was present in the application sites of animals and was accompanied by epidermal hyperplasia and hyperkeratosis. The skin application sites in all surviving animals appeared healed by two-weeks post treatment (scheduled recovery period). In all cases the sites were re-epithelialized and continuous; they also revealed mild to moderate epidermal hyperplasia and hyperkeratosis and well as normal follicular structure and population.

OTHER
A variety of inflammatory changes were also observed in kidneys, lungs and brain and, less frequently, in other organs. These were random and were interpreted as spontaneous. Other changes were too few and mild to conclusively demonstrate the presence or absence of systemic effect of the compounds tested.

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Body weight:

Most animals exhibited weight losses (0.1 to 0.4 kg) after one and/or two weeks of study. Animals held for a two weeks recovery period exhibited weight gains during this interval.

Dermal observation and pharmacologic and toxicologic signs:

Most animals exhibited slight to moderate erythema with minimal edema and no necrosis or eschar formation during the first week of study. Necrosis and eschar formation, atonia, fissuring, desquamation and exfoliation occurred subsequently (during the second week of study) in all animals. Ona animals exhibited hair loss. Dermal responses subsided in animals held for recovery. Several animals exhibited decrease food consumption during the second and third weeks of study. Other signs occurred sporadically, generally in single animals. Recovery animals were free of signs of significant toxicity at termination of the study.

Applicant's summary and conclusion

Conclusions:

Under the conditions of this test, the test compound induced severe irritation on the site of application after two weeks of exposure. Dermal irritation decreased during the post-exposure period. No other effects related to the administration of the test compound were reported.

Executive summary:

In a 28 day dermal toxicity study (Bio/dynamics, 1981), ten rabbits (5/sex) were treated with 500 mg/kg bw/day (2 ml/kg/day of a 25 % mineral oil) of heptanal for 5 days/week for 2 weeks. Four rabbits were hell for a 2 week post-exposure recovery period. Treatment did not cause mortality. Most animals lost weight during the treatment period, but gains were observed in all rabbits during the first recovery week. Moderate to severe erythema and edema, eschar and necrosis developed during the second treatment week in all animals. All dermal effects reversed during the recovery period. No significant gross or microscopic pathologies were observed.