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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11th July 1991 to 3rd August 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report date:
1993

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Propargite
EC Number:
219-006-1
EC Name:
Propargite
Cas Number:
2312-35-8
Molecular formula:
C19H26O4S
IUPAC Name:
propargite
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): Omite® Technical
- Stability under test conditions: at least one year at room temperature
- Storage condition of test material: sealed container at room temperature

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hazelton Research Products, Inc., Denver, Pennsylvania, USA
- Age at study initiation: young adult
- Weight at study initiation: 2590-3266 g
- Housing: individual suspended mesh bottom cages
- Diet: Purina® Certified Rabbit Chow® #5322 ad libitum
- Water: tap water ad libitum
- Acclimation period:a minimum of 6 days

ENVIRONMENTAL CONDITIONS
- Temperature: 65-71 ºF
- Humidity: 60-82 %
- Photoperiod: 12 hours light/12 hours dark

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL per animal
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
Three per sex
Details on study design:
OBSERVATION TIME POINTS
Application sites were observed for erythema, oedema and other dermal findings at approximately 30-60 minutes, 24, 48 and 72 hours after patch removal and daily thereafter to day 14 and on day 21.

SCORING SYSTEM:
Erythema and Eschar Formation   
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beat redness) to slight eschar formation (injuries in depth) 4

Oedema Formation
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well defined by definite raising) 2
Moderate oedema (raised approximately 1 mm) 3
Severe oedema (raised > 1mm and extending beyond area of exposure) 4

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
2.17
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritant / corrosive response data:
The test material induced moderate to severe erythema and oedema in all animals. Four sites had eschar initially on days 5, 6 and 9. Fissuring was observed on 5 sites sporadically from days 5-21. Desquamation was noted at all sites initially on days 8-11. Individual dermal irritancy scores are given in Table 1. The Primary Dermal Irritation Index was calculated to be 4.5. Mean erythema and oedema scores of 3.0 and 2.2, respectively, can be calculated for the six animals based on individual irritancy scores at 24, 48 and 72 hours.
Other effects:
There were no mortalities or significant body weight changes.

Any other information on results incl. tables

Table 1: Individual dermal irritancy scores

   Animal number (sex)
   12654 (M)  12655 (M)  12744 (M)  12658 (F)  12660 (F)  12751 (F)
   Ery  Oed  Ery  Oed  Ery  Oed  Ery  Oed  Ery  Oed  Ery  Oed
 1 h  2  0  1  1  2  0  2  1  2  1  1  0
 24 h  3  2  3  3  3  2  3  2  3  3  3  1
 48 h  3  2  3  2  3  2  3  3  3  3  3  2
 72 h  3  2  3  2  3  2  3  2  3  2  3  2
 4 d  3  2  3  3  3  2  3  2  3  2  3  2
 5 d  3  3  4  3  4  3  3  3  3  2  3  3
 6 d  3  3  4  4  4  3  4  4  3  2  3  3
 7 d  3  3  4  3  4  2  4  3  3  2  3  2
 8 d  3  3  4  4  4  3  4  3  3  2  3  2
 9 d  4  4  4  4  4  2  4  2  3  2  3  2
 10 d  4  4  4  3  4  2  4  2  3  2  3  2
 11 d  4  4  4  3  4  2  4  2  2  1  2  2
 12 d  3  2  4  2  2  1  2  1  2  1  2  2
 13 d  2  2  2  1  1  1  1  1  1  1  2  2
 14 d  2  1  2  1  1  1  2  1  2  1  2  2
 21 d  2  2  2  1  1  0  1  0  2  1  2  1

Ery = Erythema

Oed = Oedema

Applicant's summary and conclusion

Interpretation of results:
other: Category 2 in accordance with EU criteria
Conclusions:
Under the conditions of the test, the Primary Irritation Index was calculated to be 4.5.
Executive summary:

Single 0.5 mL doses of the test material were applied to the shaved, intact skin of six albino rabbits under semi-occlusive dressing for 4 hours. At completion of exposure, the bandages were removed and the sites washed. Application sites were evaluated according to Draize at approximately 30-60 minutes, 24, 48, 72 hours after patch removal and daily thereafter through to day 14 and on day 21.

There were no deaths or significant body weight changes during the study period.

Up to day 4, the test material induced moderate erythema and very slight to moderate oedema on all animals. Subsequently, severe erythema and oedema were noted on four and three sites respectively. Eschar on four sites and fissuring on five sites was initially noted on days 5-10 with the exception of fissuring that was not noted until day 21 on one animal. Desquamation was present on all sites. Very slight to slight erythema and desquamation on all sites and very slight to slight oedema on four sites was present at study termination.

The Primary Irritation Index (PII) was calculated to be 4.5. The test material received a descriptive rating of moderately irritating when interpreted in strict accordance with the protocol. However, the highest levels of irritation were not observed until days 5-9 which are intervals not used in the calculation of PII. Therefore the irritation potential of the test material may be greater than that arrived at by classification based solely on the PII due to the delayed reactions that were observed.

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