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Description of key information

Propargite was determined to be irritating to skin and eyes; studies conducted in accordance with EPA OPP 81-5 and 81-4; Kiplinger (1993c; 1993d)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
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
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
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
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
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.

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

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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
22nd July 1991 to 19th August 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
EPA OTS 798.4500 (Acute Eye Irritation)
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hazelton Research Products, Inc., Denver, Pennsylvania, USA
- Age at study initiation: young adult
- Weight at study initiation: 3072-3324 g
- Housing: individually suspended mesh-bottom cages
- Diet: Purina® Certified Rabbit Chow® #5322 ad libitum
- Water: tap water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 66-76 ºF
- Humidity: 50-88 %
- Photoperiod: 12 hours light/12 hours dark
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
Eyelid closed for approximately one second
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
1 male, 5 females
Details on study design:
OCULAR OBSERVATIONS
Both eyes of all rabbits were examined for ocular abnormalities prior to the study initiation. The pre-initiation examination included the use of sodium fluorescein and ultraviolet light.
Both eyes of all rabbits were examined macroscopically for ocular irritation using a hand-held penlight in accordance with the method of Draize at approximately 1, 24, 48 and 72 hours after dosing and at 4, 7, 10, 14, 17 and 21 days if irritation persisted. In addition, both eyes of all rabbits were further examined at 72 hours and 7, 10, 14, 17 and 21 days with sodium fluorescein and ultraviolet light.

SCORING SYSTEM:
(1) Cornea
(A) Opacity-degree of density
No ulceration or opacity 0
Dulling of normal luster,details of iris clearly visible 1
Easily discernible translucent areas, details of iris slightly obscured 2
Nacerous areas, no details of iris visible, size of pupil barely discernible 3
Opaque cornea, iris not discernible through opacity 4

(B) Area of cornea involved
No ulceration or opacity 0
One quarter or less but not zero 1
Greater than one quarter, but less than half 2
Greater than half, but less than three quarters 3
Greater than three quarters, up to whole area 4

(2) Iris
(A) Values
Normal 0
Markedly deepened rugae, congestion, swelling, circumcorneal injection (any or all of these of combination of any thereof) 1
No reaction to light, haemorrhage, gross destruction (any or all) 2

(3) Conjunctivae
(A) redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
Blood vessels normal 0
Some blood vessels definitely hyperemic (injected above) normal 1
Diffuse, deeper crimson colour, individual vessels not easily discernible 2
Diffuse beefy red 3

(B) Chemosis: kids and /or nicitating membranes
No swelling 0
Any swelling above normal 1
Obvious swelling with partial eversion of lids 2
Swelling with lids about half closed 3
Swelling with lids more than half closed 4

(C) Discharge
No discharge 0
Any amount different from normal 1
Discharge with moistening of the lids and hairs just adjacent to the lids 2
Discharge with moistening of the lids and hair and considerable area around the eye 3
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
24/48/72 h
Score:
1.9
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.39
Max. score:
2
Reversibility:
not fully reversible within: 10 days
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0.22
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
2.94
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritant / corrosive response data:
Positive conjunctival reactions were observed in the treated eyes of all animals. Corneal and iridial reactions were observed in the right eye of three and four rabbits, respectively. Corneal and iridial irritation subsided by day 10 or earlier. Conjunctival irritation was seen in all six rabbits and subsided by day 21 or earlier. Conjunctival irritation only persisted to day 21 in three animals and this was considered to be minor and reversible (see Table 1). Mean scores of 2.9, 1.9, 0.39 and 0.22 can be calculated for conjunctival chemosis, conjunctival redness, iridial lesion and corneal opacity, respectively, 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.

Table 1: Individual ocular irritancy scores

 Animal (sex)  Tissue  1 h  24 h  48 h  72 h  4 d  7 d  10 d  14 d  17 d  21 d
 12701 (M)  Cornea (O-A)  0 0  0 0  0 0  0 0  0 0  1 1  0 0  0 0  0 0  0 0
   Iris  0  0  0  0  0  0  0  0  0  0
   Conjunctivae (R-C-D)  1 1 0  2 2 1  2 2 1  2 3 2  2 4 2  2 4 1  1 4 0  1 2 0  1 2 0  0 1 0
 12702 (F)  Cornea (O-A)  0 0  0 0  0 0  0 0  0 0  0 0  0 0  0 0  0 0  0 0
   Iris  0  0  0  1  0  0  0  0  0  0
   Conjunctivae (R-C-D)  1 1 1  2 3 1  2 3 1  1 3 1  1 3 1  1 4 1  1 4 1  1 2 0  1 2 0  0 0 0
 12705 (F)  Cornea (O-A)  0 0  0 0  1 2  1 2  1 2  1 2  0 0  0 0  0 0 0 0
   Iris  0  1  1  1  1  1  0  0  0  0
   Conjunctivae (R-C-D)  1 1 1  2 2 2  2 4 2  2 4 1  2 4 1  1 4 1  1 4 1  1 2 0  1 2 0  1 1 0
 12716 (F)  Cornea (O-A)  0 0  0 0  0 0  0 0  0 0  0 0  NA  0 0  0 0 0 0
   Iris  0  0  0  0  0  0  NA  0  0  0
   Conjunctivae (R-C-D)  2 2 0  2 3 1  2 3 1  2 3 2  2 4 2  1 4 1  NA  1 2 0  0 1 0  0 0 0
 12722 (F)  Cornea (O-A)  0 0  0 0  1 1  1 2  1 2  1 2  0 0  0 0  0 0  0 0
   Iris  0  1  1  1  1  1  0  0  0  0
   Conjunctivae (R-C-D)  1 0 2  1 2 1  2 3 2  2 3 2  1 4 2  1 4 1  1 4 0  1 2 0  0 2 0  0 1 0
 12723 (F)  Cornea (O-A)  0 0  0 0  0 0  0 0  0 0  0 0  0 0  0 0  0 0  0 0
   Iris  0  0  0  0  0  1  0  0  0  0
   Conjunctivae (R-C-D)  1 1 0  2 3 1  2 3 1  2 4 2  2 4 1  1 4 1  1 4 0  1 2 0  1 1 0  0 0 0
Interpretation of results:
other: Category 1 in accordance with EU criteria
Conclusions:
Under the conditions of the test, mean scores of 2.9, 1.9, 0.39 and 0.22 can be calculated for conjunctival chemosis, conjunctival redness, iridial lesion and corneal opacity, respectively, for the six animals, based on individual irritancy scores at 24, 48 and 72 hours.
Executive summary:

0.1 mL of test material was instilled into the lower conjunctival sac of the right eyes of six albino rabbits. The eyelids were held closed for approximately 1 second and released. Left eyes served as contralateral controls.

The eyes were examined for ocular reactions in accordance with the method of Draize at approximately 1, 24, 48 and 72 hours after dosing and at 4, 7, 10, 14, 17 and 21 days if irritation persisted. Sodium fluorescein was used to aid in revealing possible corneal damage at 72 hours, 7, 10, 14, 17 and 21 days.

Positive conjunctival reactions were noted in the treated eye of all animals. Corneal and iridal reactions were observed in the right eye of three and four rabbits, respectively. Corneal and iridal irritation subsided by day 10 or earlier. Positive conjunctival irritation subsided by 21 or earlier. Minor conjunctival irritation not considered a positive score persisted through day 21 for three animals.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a GLP compliant skin irritation study conducted in accordance with a standardised guideline, the skin irritation of the test material was determined. Under the conditions of the test, the test material was determined to be irritating to skin.

In a GLP compliant eye irritation study conducted in accordance with a standardised guideline, the eye irritation of the test material was determined. Under the conditions of the test, the test material was determined to be irritating to eyes.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance requires classification with respect to skin irritation as Category 2 (H315: Causes skin irritation) eye irritation as Category 1 (H318: Causes serious eye damage).

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