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Toxicological information

Repeated dose toxicity: dermal

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Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report which meets basic scientific principles: pre-GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1964
Report Date:
1964

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Test substance was applied to animals once a day for 10 days with a rest period between the fifth and sixth applications.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): MRD-64-3
- Physical state: liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Housing: individually
- Diet (e.g. ad libitum): chow ad libitum
- Water (e.g. ad libitum): ad libitum

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on exposure:
Route of Administration: dermal
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.5 ml/kg at doses of 0.5 or 2.5 ml/kg (400 or 2280 mg/kg-bw/day, respectively)
- Concentration (if solution): assumed 100%
- Constant volume or concentration used: yes
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
10 daily applications with a two-day rest between the 5th and 6th applications.
Frequency of treatment:
Daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0.5 or 2.5 ml/kg
Basis:
nominal per unit body weight
No. of animals per sex per dose:
4
Control animals:
other: isopropyl alcohol at 2.5 ml/kg
Positive control:
Isopropyl alcohol

Examinations

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

DETAILED CLINICAL OBSERVATIONS: Yes / No / No data
- Time schedule:

DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: daily for signs of irritation

BODY WEIGHT: Yes
- Time schedule for examinations: study termination

HAEMATOLOGY: Yes
- Time schedule for collection of blood: initially and prior to the final application
- Parameters checked in table: total erythrocyte count, total and differential leukocyte count, hematocrit.

NECROPSY
- Brain, thyroid, lungs, heart, liver, kidneys, adrenals, skin, bone marrow.
Sacrifice and pathology:
HISTOPATHOLOGY: Yes, liver and kidney
Other examinations:
N/A
Statistics:
N/A

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:
effects observed, treatment-related
Clinical biochemistry findings:
effects observed, treatment-related
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
GENERAL APPEARANCE AND BEHAVIOR
Wheezing was noted in one animal at the 0.5 ml dose level. Animals at the lower dose level generally showed an overall body weight gain while those at the high level showed terminal weight losses.

DERMAL IRRITATION
The low level animals generally showed slight erythema and moderate atonia and desquamation following the first or fourth application and during the remainder of the study. At the high level, moderate erythema and moderate or marked atonia and desquamation were present in all animals. In addition, slight edema was present following the fifth application and slight fissures or cracks were observed in several animals following the last seven applications. The exposed skin also became hypersensitive to the touch.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Remarks:
Systemic effects
Effect level:
2.5 other: ml/kg
Sex:
male
Basis for effect level:
other: No adverse effects related to treatment.
Dose descriptor:
LOAEL
Remarks:
Local effects
Effect level:
0.5 other: ml/kg
Sex:
male
Basis for effect level:
other: Skin irritation.

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

0.5 ml/kg 2.5 ml/kg
24 hours after application No. Erythema Atonia Desquamation Erythema Edema Atonia Desquamation Fissures
1 + (4) + (4)
2 (4) ++(4)
3 + (4) + (4) + (4) ++(4) ++(4)
4 + (4) ++(4) ++(2)+(2) ++(4) ++(4) + (4) +(1)
5 + (4) ++(4) ++(4) ++(4) + (4) +++(3)++(1) +++(2)++(2) +(1)
6 + (4) ++(4) ++(4) ++(3)+(1) +++(3)++(1) +++(3)++(1) +(4)
7 + (4) ++(4) ++(4) ++(4) +++(3)++(1) +++(4) +(2)
8 ++(1)+(3) ++(4) ++(4) ++(4) +++(3)++(1) +++(4) +(2)
9 ++(1)+(3) ++(4) ++(4) ++(4) +++(4) +++(4) +(2)
10 ++(1)+(3) ++(4) ++(4) ++(4) +++(4) +++(3)++(1) +(2)
Key: + = slight; ++ = moderate; +++ = severe; number in paraenthesis is number of animals showing the sign.

Applicant's summary and conclusion

Conclusions:
No NOAEL was identified; no adverse systemic effects were reported.
Executive summary:

In this study, neodecanoic acid was applied repeatedly (once daily for 10 applications with a rest period on days 5 and 6) to the skin of rabbits at doses of 0.5 or 2.5 ml/kg.  All animals survived the exposure.  Wheezing was noted in one animal at the 0.5 ml dose level.  Animals at the lower dose level generally showed an overall body weight gain while those at the high level showed terminal weight losses.  The low level animals generally showed slight erythema and moderate atonia and desquamation following the first or fourth application and during the remainder of the study.  At the high level, moderate erythema and moderate or marked atonia and desquamation were present in all animals.  In addition, slight edema was present following the fifth application and slight fissures or cracks were observed in several animals following the last seven applications.  The exposed skin also became hypersensitive to the touch. There were no indications of systemic toxicity are attributable to exposure.