Registration Dossier

Toxicological information

Exposure related observations in humans: other data

Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1979
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Documentation insufficient for assessment
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Study period:
1979
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Study was conducted according to a non-standard method, appplying 0.05 g of test material instead of 0.5 g. Documentation was insufficient for assessment.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Principles of method if other than guideline:
A group of 6 miniature swine were dermally exposed to the test material, under a patch, for 48 h and then scored for irritation reactions.
GLP compliance:
not specified
Species:
other: miniature swine
Strain:
other: Pitman-Moore Improved strain
Details on test animals and environmental conditions:
No data
Type of coverage:
occlusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.05 g
Duration of treatment / exposure:
Single treatment (48 h exposure)
Observation period:
48 h after application of test material
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: dorsal surface
- % coverage: 15 mm diameter patch
- Type of wrap if used: adhesive tape. The entire trunk of the animal was then wrapped with rubberized cloth for the 48 h period of exposure.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data
- Time after start of exposure: 48 hours

HISTOPATHOLOGY:
After scoring, all animals were killed and the dorsal skin was removed. Specimens of all animal skins were fixed in 10 % formalin solution. Celloidin-paraffin embedding was performed. 5 µ thick specimens were stained with hematoxylin-eosin for microscopic observation.

SCORING SYSTEM
Evaluation of skin reactions were performed as follows
1. On the living skin
Reddening rate (erythema)
- : no reddening
± : very slight reddening {barely perceptible}
+ : well defined reddening
++ : moderate reddening
+++: severe reddening (beet redness)
Others: scaling, crust formation, loss of elasticity and fissures
2. On the removed skin
dilating rate
swelling rate (edema)
bluing rate (increased capillary permeability)
bleeding rate
3. Total score
Total score (72 h reading) = dilating rate + swelling rate + bluing rate + reddening rate
Irritation parameter:
other: total score
Basis:
mean
Remarks:
all animals
Time point:
48 h
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
None
Other effects:
No data

None

Conclusions:
Under the test conditions, topical application of gamma-undecalactone did not induce skin irritation in miniature swine.
Executive summary:

In a primary dermal irritation study, a group of 6 miniature swine of the Pitman-Moore Improved strain was dermally exposed to gamma-undecalactone (0.05 g) on dorsal surface of each animal under a 15 mm diameter patch. The patches were secured in place by adhesive tape. The entire trunk of the animal was then wrapped with rubberized cloth for the 48 h period of exposure. After 48 h exposure the patches were removed and reactions were observed.

Gamma-Undecalactone did not induce skin irritation in miniature swine and the irritation score was 0.

Under the test conditions, topical application of gamma-undecalactone did not induce skin irritation in miniature swine. This study was conducted according to a non-standard method and documentation was insufficient for assessment.

Reason / purpose:
reference to same study
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Study period:
1979
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Study was conducted according to a non-standard method , involving repeated exposure. Documentation was insufficient for assessment.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Principles of method if other than guideline:
A group of 6 rabbits were dermally exposed to the test material and skin reactions were recorded at 24, 48 and 72 h after first, second and third application, respectively. After the 72 h reading, skin was removed and processed for evaluation of skin reactions and histopathological examinations.
GLP compliance:
not specified
Species:
rabbit
Strain:
Angora
Details on test animals and environmental conditions:
None
Type of coverage:
open
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 g
Duration of treatment / exposure:
3 days
Observation period:
Skin reactions were recorded at 24, 48 and 72 h after first, second and third application, respectively.
Number of animals:
6
Details on study design:
- Test material was kept in contact with the animals for 24 h. After 24 h reading, the hair on the test area was clipped and the test compound was again applied 30 minutes later. A second set of reading and application was made 48 h later. After the 72 h reading, all the hair on the dorsal surface of each animal was clipped.
- Animals were killed, the dorsal skin was removed and evaluation of skin reactions was performed using Evans blue.
- Histopathological examination: Specimens of all animal skins were fixed in 10 % formalin solution. Celloidin-paraffin embedding was performed. 5 µ thick specimens were stained with hematoxylin-eosin for microscopic observation.
- Scoring system: Evaluation of skin reactions were performed as follows:
1. On the living skin
Reddening rate (erythema)
- : no reddening
± : very slight reddening (barely perceptible)
+ : well defined reddening
++ : moderate reddening
+++: severe reddening (beet redness)
Others: scaling, crust formation, loss of elasticity and fissures
2. On the removed skin
dilating rate
swelling rate (edema)
bluing rate (increased capillary permeability)
bleeding rate
3. Total score
Total score (72 h reading) = dilating rate + swelling rate + bluing rate + reddening rate
Irritation parameter:
other: total score
Basis:
mean
Remarks:
all animals
Time point:
72 h
Score:
3
Max. score:
3
Reversibility:
no data
Remarks on result:
positive indication of irritation
Remarks:
severe skin irritation
Irritant / corrosive response data:
None
Other effects:
No data

None

Conclusions:
Under the test conditions, topical application of gamma-undecalactone induced severe skin irritation in rabbits.
Executive summary:

In a primary dermal irritation study, a group of 6 angora rabbits was dermally exposed to gamma-undecalactone (0.1 g) on the dorsal, mid-lumbar region (3 x 3 cm). The opposite site was left untreated. Test material was kept in contact with the animals for 24 h. After 24 h reading, the hair on the test area was clipped and the test compound was again applied 30 minutes later. A second set of reading and application was made 48 h later. After the 72 h reading, animals were killed, the dorsal skin was removed and evaluation of skin reactions was performed using Evans blue solution. Removed skin was also processed for histopathological examinations.

Gamma-undecalactone induced severe skin irritation in rabbits and the total irritation score was 3.

Under the test conditions, topical application of gamma-undecalactone induced severe skin irritation in rabbits. This study was conducted according to a non-standard method, involving repeated exposure, and documentation was insufficient for assessment.

Reason / purpose:
reference to same study
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Study period:
1979
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Study was conducted according to a non-standard method , involving repeated exposure. Documentation was insufficient for assessment.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Principles of method if other than guideline:
A group of 6 guinea pigs were dermally exposed to the test material and skin reactions were recorded at 24, 48 and 72 h after first, second and third application, respectively. After the 72 h reading, skin was removed and processed for evaluation of skin reactions and histopathological examinations.
GLP compliance:
not specified
Species:
guinea pig
Strain:
Hartley
Details on test animals and environmental conditions:
None
Type of coverage:
open
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 g
Duration of treatment / exposure:
3 days
Observation period:
Skin reactions were recorded at 24, 48 and 72 h after first, second and third application, respectively.
Number of animals:
6
Details on study design:
- Male Hartley guinea pigs were treated dermally with 0.1 g of 100 % gamma-undecalactone on the dorsal, mid-lumbar region (3 x 3 cm). The opposite site was left untreated.
- Test material was kept in contact with the animals for 24 h. After 24 h reading, the hair on the test area was clipped and the test compound was again applied 30 minutes later. A second set of reading and application was made 48 h later. After the 72 h reading, all the hair on the dorsal surface of each animal was clipped.
- Animals were killed, the dorsal skin was removed and evaluation of skin reactions was performed using Evans blue.
- Histopathological examination: Specimens of all animal skins were fixed in 10 % formalin solution. Celloidin-paraffin embedding was performed. 5 µ thick specimens were stained with hematoxylin-eosin for microscopic observation.
- Scoring system: Evaluation of skin reactions were performed as follows:
1. On the living skin
Reddening rate (erythema)
- : no reddening
± : very slight reddening (barely perceptible)
+ : well defined reddening
++ : moderate reddening
+++: severe reddening (beet redness)
Others: scaling, crust formation, loss of elasticity and fissures
2. On the removed skin
dilating rate
swelling rate (edema)
bluing rate (increased capillary permeability)
bleeding rate
3. Total score
Total score (72 h reading) = dilating rate + swelling rate + bluing rate + reddening rate
Irritation parameter:
other: total score
Basis:
mean
Remarks:
all animals
Time point:
72 h
Score:
2
Max. score:
3
Reversibility:
no data
Remarks on result:
positive indication of irritation
Remarks:
moderate skin irritation
Irritant / corrosive response data:
None
Other effects:
No data

None

Conclusions:
Under the test conditions, topical application of gamma-undecalactone induced moderate skin irritation in guinea pigs.
Executive summary:

In a primary dermal irritation study, a group of 6 male Hartley guinea pigs was dermally exposed to gamma-undecalactone (0.1 g) on the dorsal, mid-lumbar region (3 x 3 cm). The opposite site was left untreated. Test material was kept in contact with the animals for 24 h. After 24 h reading, the hair on the test area was clipped and the test compound was again applied 30 minutes later. A second set of reading and application was made 48 h later. After the 72 h reading, animals were killed, the dorsal skin was removed and evaluation of skin reactions was performed using Evans blue solution. Removed skin was also processed for histopathological examinations.

Gamma-undecalactone induced moderate skin irritation in guinea pigs and the total irritation score was 2.

Under the test conditions, topical application of gamma-undecalactone induced moderate skin irritation in guinea pigs. This study was conducted according to a non-standard method and documentation was insufficient for assessment.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1979

Materials and methods

Type of study / information:
Skin irritation score
Endpoint addressed:
skin irritation / corrosion
Principles of method if other than guideline:
A panel of 50 adult male volunteers were dermally exposed to the test material, under a patch, for 48 h and then scored for irritation reactions.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Gamma-undecalactone
- Analytical purity: >95 %
- Storage condition of test material: Kept in light-intercepting ampoules at 5 °C
- Stability under test conditions: No detectable changes in compositions were observed during the experiment.

Method

Details on study design:
- A panel of 50 adult male volunteers was dermally exposed to 0.05 mL of gamma-undecalactone (32 % in acetone) under a 15 mm lint patch.
- Individuals with known allergic reactions were excluded.
- Patches were placed in contact with the skin on the back of each subject and left for 48 h.
- Patches were then removed and the sites were swabbed with dry gauze to remove any residual test materials. 30 minutes later, the test sites were evaluated for dermal reactions. If necessary, 72, 96 and 120 h readings were performed.

- Scoring of patch test reactions:
-: negative reading
±: questionable erythema not covering the entire patch area
+: definite erythema of the entire patch area
++: erythema and edema
+++: erythema, edema, and vesicles (or papules)
++++: bullous reaction
Exposure assessment:
measured

Results and discussion

Results:
Gamma-undecalactone did not induce the skin irritation in human and the irritation score was 0.

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:
Under the test conditions, topical application of γ-Undecalactone did not induce skin irritation in human. This study was conducted according to a non-standard method and documentation was insufficient for assessment.
Executive summary:

In a dermal irritation study, a panel of 50 adult male volunteers was dermally exposed to 0.05 mL of γ-Undecalactone (32 % in acetone) under a 15 mm lint patch. Individuals with known allergic reactions were excluded. The patches were placed in contact with the skin on the back of each subject and left for 48 h. The patches were then removed and the sites were swabbed with dry gauze to remove any residual test materials. After 30 minutes, the test sites were evaluated for dermal reactions. If necessary, 72, 96 and 120 h readings were performed.

γ-Undecalactone did not induce the skin irritation in human and the irritation score was 0.

Under the test conditions, topical application of γ-Undecalactone did not induce skin irritation in human. This study was conducted according to a non-standard method and documentation was insufficient for assessment.