Fatty acids, C6-19-branched, zinc salts

Repeated dose toxicity: dermal

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

Test material information

Constituent 1

Reference substance name:

Neodecanoic acid

EC Number:

248-093-9

EC Name:

Neodecanoic acid

Cas Number:

26896-20-8

IUPAC Name:

2-ethyl-2,5-dimethylhexanoic acid

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 or test system 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

1

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.

2

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.