Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No OECD-Guideline dose-range finding study but of reliable qualitiy and conducted according to GLP
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: EPA TSC Health Effects Test Guideline (OTS 1983)
Qualifier:
according to
Guideline:
other: EPA Pesticide Assessment Guidelines-Subdivision F-Hazard Evaluation, 1982
GLP compliance:
yes (incl. certificate)
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): (Z)-9-octadecenylamine

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: in-house breeding station at Intox
- Age at study initiation: young adults
- Weight at study initiation: 206 - 321 g
- Fasting period before study: no
- Housing: stainless-steel cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: approx 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 22 °C
- Humidity (%): 40 - 56
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light): 12 hours periodically

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
other: mineral oil
Details on exposure:
TEST SITE
- Area of exposure: 10 %
- % coverage: 100
- Type of wrap if used: porous gauze covered with Vetwrap elastic bandage
- Time intervals for shavings or clipplings: 7 days

REMOVAL OF TEST SUBSTANCE
- Washing (if done): daily
- Time after start of exposure: 6 hours after test article apllication

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5 mL/kg
- Concentration (if solution): 0, 0.3, 1.5 and 3%
- Constant volume or concentration used: yes
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Two 5-days periods with an intermediate 2-day non-dosing period
Frequency of treatment:
daily, 5 days per week, 2 weeks
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0 %
Basis:
nominal per unit area
Remarks:
Doses / Concentrations:
0.3 %
Basis:
nominal per unit area
Remarks:
Doses / Concentrations:
1.5 %
Basis:
nominal per unit area
Remarks:
Doses / Concentrations:
3.0 %
Basis:
nominal per unit area
No. of animals per sex per dose:
4
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: based on pilot study
- Rationale for animal assignment (if not random): random
- Rationale for selecting satellite groups: no satellite groups
- Post-exposure recovery period in satellite groups: n.a.
- Section schedule rationale (if not random): n.a.
Positive control:
no

Examinations

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

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily

DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: days 2, 4, 6, 8, 10, 12 and 14 (first dosing day = day 1)

BODY WEIGHT: Yes
- Time schedule for examinations: prior to study initiation, weekly thereafter

FOOD CONSUMPTION:
- Food consumption: determined weekly

OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: No data

CLINICAL CHEMISTRY: No data

URINALYSIS: No data
Sacrifice and pathology:
GROSS PATHOLOGY: No data
HISTOPATHOLOGY: No

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Dermal irritation:
effects observed, treatment-related
Description (incidence and severity):
erythema at lowest test concentration; necrosis at mid- and high dose
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
weight loss in females of highest dose during first week
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
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 examined
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
not examined

Effect levels

Dose descriptor:
LOAEL
Remarks:
local dermal effects
Effect level:
0.3 other: %
Sex:
male/female
Basis for effect level:
other: dermal irritation responses

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Based on mild to moderate dermal irritation observed in all dose groups, a NOAEL for local effects could not be established. Based on the grading of dermal effects, the lowest dosage of 0.3% (v/v) is regarded to be a LOAEL.
Executive summary:

Octadecenylamine (oleylamine) was dermally applied on two 5-days periods with intermediate 2-day non dosing-period to male and female Sprague-Dawley rats (Intox Laboratories, 1985). Animals of the control groups received the vehicle only (mineral oil).

Based on the results of a pilot study, groups of young adult rats (4 males and 4 females) were treated dermally with the test substance at concentrations of 0, 0.3, 1.5 and 3.0% (v/v) in mineral oil (corresponding to doses of 0, 12.5, 62.5 and 125 mg/kg bw/d). Rats were treated for two five-day dosing periods with an intermediate two-day non-dosing period in order to more closely reproduce conditions of human exposure to the test substance. The first day of dosing was designated as Day 1. Due to excessive tissue destruction indicated by sloughing, scores of moderate to severe erythema, scabbing, hardening of the skin, and sensitivity to touch, the dosing at the intermediate and high dose levels (1.5 and 3.0%) was discontinued on Day 9. These animals were subsequently sacrificed on Day 10. At initiation of dosing the rats’ body weights ranged from 205.7 to 321.3 g. Rats were acclimated to the laboratory for seven days prior to test substance application. Water and food were provided ad libitum. Approximately 24 hours prior to test substance application, the fur was clipped from the dorsal area of each animal. Shaving was repeated one week later. The test substance was applied at a volume dosage of 5 ml/kg. The application site was covered by a porous gauze dressing that was held in place with tape, and covered with a taped elastic bandage. Each day, wrappings were removed approximately six hours after test substance application and the test sites were washed with warm water to remove excess test substance. Observations of signs of toxicity were made once each day. Body weights were recorded during acclimation, weekly during the study and at sacrifice. Food consumption was recorded weekly during the study. Morbidity/mortality checks were examined prior to test substance administration on days 2, 4, 6, 8, 10, 12 and 14 for signs of erythema and necropsies were performed. Animals were killed and discarded three days following the completion of dosing.

All rats survived until scheduled sacrifice. Concentrations of 1.5 and 3.0% produced moderate to severe irritation (erythema scores 2-4), which in some instances progressed to hardening and sloughing of the skin. A number of rats were sensitive to touch. In the 0.3 % group, erythema scores of 1 to 2 were observed, indicating mild to moderate irritation, and flaking of the outer layers of the epidermis was observed. An increased sensitivity in females to the irritant effects of the test substance as compared to males was observed. In the control group, one male showed an erythema score of 1 at one observation. All rats in the 1.5 and 3% groups were sacrificed on day 9 of the study due to the irritant/corrosive effects of the test substance. No other treatment-related irritant effects or clinical signs were observed. A significant treatment-related effect on body weight was observed for males at day 7. Individual group comparisons revealed that body weights in both the 1.5 and 3% groups were significantly lower than controls. Females in the 3.0% group showed a mean weight loss during the first week of the study, although this finding was not significant. Food consumption during the first week of study was reduced significantly in the 1.5% group males when expressed as total food consumed. No significant difference was noted when expressed on a per weight basis. The study provides additional data on the toxicity of repeated dermal dosing, including severe irritation, of this test substance at concentrations of 0.3, 1.5 and 3.0%. A NOAEL for local dermal effects could not be derived, the LOAEL was 0.3% (v/v). No NOAEL for systemic toxicity was derivable because of lack of histomorphology data from other organs and tissues.