Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
No data
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Older proprietary study conducted prior to development of GLP and test guideline. Reporting is considered minimal, and the methodology is not comparable to the recommended guideline.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1971
Report date:
1971

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The study was conducted prior to adoption of the current test guidelines. Four rabbits (2/sex) were exposed to a limit dose of the test substance for 24 hours. The application site in 1 rabbit/sex was abraded prior to application.
GLP compliance:
no
Remarks:
Conducted prior to development of GLP
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
aurantium
IUPAC Name:
aurantium
Constituent 2
Reference substance name:
RIFM 71-32
IUPAC Name:
RIFM 71-32
Test material form:
liquid: viscous
Details on test material:
- Name of test material (as cited in study report): RIFM 71-32
- Physical state: clear yellow viscous liquid
- Lot/batch No.: 5-11-71

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: 1.9 to 3.3 kg

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: A single application of test material was made to the clipped intact and abraded skin of the backs and flanks of each animal, at a dose of 10 mL/kg bw. The application site of one male and one female from each group was prepared by making epidermal abrasions every 2-3 cm longitudonally over the exposure area. The abrasions penetrated the stratum corneum, but not the dermis.
- Type of wrap if used: The test substance was applied beneath dental dam binders which were placed around the trunk of each animal. The trunk was then covered with a gauze and adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Test sites were sponged with warm tap water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 mL/kg bw
- Concentration (if solution): Applied undiluted
Duration of exposure:
24 hours
Doses:
10 mL/kg bw (equivalent to approximately 10000 mg/kg bw)
No. of animals per sex per dose:
2/sex
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: Observations for signs of toxicity, mortality and dermal irritation were made once daily following removal of the dental dam, for 14 days. Body weights were recorded prior to dosing, and again at 14 days.
- Necropsy of survivors performed: Yes (Day 14).
- Other examinations performed: Clinical signs, body weight, dermal irritation.
Statistics:
Not required.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Based on a dose of 10 mL/kg bw
Mortality:
No mortalities occurred.
Clinical signs:
No clinical signs were noted during the study.
Body weight:
Body weight gain averaged 0.5 kg over the 14 day observation period.
Gross pathology:
No abnormalities were detected at necropsy.
Other findings:
Dermal irritation was observed at the test sites. Well-defined to moderate erythema and very slight to slight oedema were noted 24 hours after test substance removal, at the intact skin sites. The oedema cleared by Day 4 and the erythema cleared by Day 10. Well-defined to moderate erythema and slight oedema were noted at the abraded test sites, persisting until study termination; slight to well-defined erythema and slight oedema were noted at the final observation.

Any other information on results incl. tables

The acute dermal LD50 of the test material was reported to be > 10 mL/kg bw, equivalent to approximately >10000 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the study, the acute dermal LD50 was estimated to be greater than 10 mL/kg bw, equivalent to approximately 10000 mg/kg bw.
Executive summary:

The acute dermal toxicity of aurantiol pure (RIFM 71 -32) was investigated in a group of two male and two female New Zealand White rabbits. The test substance was applied to the clipped back skin of each rabbit and held in place under an occlusive dressing for 24 hours. A dose of 10 mL/kg bw was applied to each rabbit. The test site was abraded on 1 male and 1 female prior to application. The rabbits were observed for signs of toxicity, mortality and dermal irritation daily for 14 days following application. Gross necropsies were performed on all animals at study termination (Day 14). There were no mortalities, and no clinical signs of toxicity were observed during the study. Well-defined to moderate erythema and slight to moderate oedema was observed in all rabbits. Dermal irritation had cleared by Day 10 in the intact sites, but persisted to Day 14 in the abraded test sites. No abnormalities were detected at necropsy.

Under the conditions of the study, the acute dermal LD50 was estimated to be greater than 10 mL/kg bw, equivalent to approximately 10000 mg/kg bw.