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Administrative data

Description of key information

There are two reliable studies available covering dermal and eye irritation potential in rabbits. Among them an acute eye irritation/corrosion study according to OECD 405 and an acute dermal irritation study according to OECD 404. Acetoguanamine is shown to be non irritating.

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:
1989-10-31 till 1989-11-03
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Reliable without restrictions; Guideline study (OECD 404; Irritant effects on rabbit skin) according to GLP.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
not specified
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Froxfield Farms (U.K.) Ltd., Petersfield, Hampshire, England
- Age at study initiation: approx. 12 weeks
- Weight at study initiation: 2.5 - 2.7 kg
- Housing: idividually in metal cages with perforated floors.
- Diet (e.g. ad libitum): SDS Standard Rabbit Diet (ad libitum)
- Water (e.g. ad libitum): tap water (ad libitum)
- Acclimation period: "the rabbit selected were all acclimated to the laboratory environment", but no data on time period.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): approx. 19 °C
- Humidity (%): 30-70 %
- Air changes (per hr): approx. 19 per hour
- Photoperiod (hrs dark / hrs light): lighting was controlled by means of a time switch to give 12 hours of artificial light (0700-1900 hours) in each 24 hours period.
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g Acetoguanamine

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL distilled water
- Lot/batch no. (if required): 10/08/89 AG
- Purity: 99.2 %
Duration of treatment / exposure:
four hours
Observation period:
Examintation of the treated skin was made on Day 1 (i.e. approximately 30 minutes after removal of the patches) and on Days 2, 3 and 4.
Number of animals:
three
Details on study design:
TEST SITE
- Area of exposure: dorso-lumbar region
- Type of wrap if used: 2.5 cm square gauze pad

REMOVAL OF TEST SUBSTANCE
- Washing (if done): treatment site was washed using water to remove any residual test substance
- Time after start of exposure: four hours

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

Oedema formation:
0: No oedema
1: Very slight oedema (barely perceptible)
2: Slight oedema (edges of area well-defined by definite raising)
3: Moderate oedema (raised approximately 1 millimetre)
4: Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 30 minutes after removal of the patches and on days 2, 3 and 4
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 30 minutes after removal of the patches and on days 2, 3 and 4
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 30 minutes after removal of the patches and on days 2, 3 and 4
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 30 minutes after removal of the patches and on days 2, 3 and 4
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 30 minutes after removal of the patches and on days 2, 3 and 4
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 30 minutes after removal of the patches and on days 2, 3 and 4
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
The treated skin of all three animals was scored for erythema and oedema. The test substance caused no adverse effects to the skin.
Other effects:
None of the animals showed any response to treatment throughout the observation period.

Table 1: Dermal reactions elicited by Acetoguanamine.

Rabbit Number and Sex

Bodyweight

(Day 1)

E = Erythema

O = Oedema

Day

1*

2

3

4

803 (female)

2525 g

E

O

0

0

0

0

0

0

0

0

804(female)

2650 g

E

O

0

0

0

0

0

0

0

0

805(female)

2670 g

E

O

0

0

0

0

0

0

0

0

* Approximately 30 minutes after removal of the dressing

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: EEC Directive 83/467/EEC Annex VI Part II
Conclusions:
In a dermal irritation study according to OECD 404 three New Zealand White strain rabbits were semi-occlusive dermally exposed to 0.5 g Acetoguanamine for four hours. Examination of the treated skin was made on Day 1 (i.e. approx. 30 minutes after removal of the test substance) and on Day 2, 3 and 4. None of the animals showed any response to treatment throughout the observation period.
Therefore no classification for skin irritation is required for Acetoguanamine.
Executive summary:

In a dermal irritation study according to OECD 404 three New Zealand White strain rabbits were semi-occlusive dermally exposed to 0.5 g of Acetoguanamine for four hours. Examination of the treated skin was made on Day 1 (i.e. approx. 30 minutes after removal of the test substance) and on Day 2, 3 and 4. None of the animals showed any response to treatment throughout the observation period. Therefore no classification for skin irritation is required for Acetoguanamine.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not 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:
1989-11-06 till 1989-11-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Reliable without restrictions; Guideline study (OECD 405) according to GLP
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Froxfield Farms (U.K.) Ltd., Petersfield, Hampshire, England.
- Age at study initiation: 12 to 13 weeks of age
- Weight at study initiation: 2.8 to 3.0 kg
- Housing: individually housed in metal cages with perforated floors
- Diet (e.g. ad libitum): free access to SDS Standard Rabbit Diet
- Water (e.g. ad libitum): free access to tap water
- Acclimation period: yes, but no period of time mentioned

ENVIRONMENTAL CONDITIONS
- Temperature (°C): approx. 19 °C
- Humidity (%): 30-70 %
- Air changes (per hr): 19 air changes per hour
- Photoperiod (hrs dark / hrs light): lightning was controlled to give 12 hours of artificial light (0700-1900 hours) in each 24 hour period.
Vehicle:
not specified
Controls:
not required
Amount / concentration applied:
Approx. 85 mg of Acetoguanamine, the weight occupying a volume of 0.1 ml.
Duration of treatment / exposure:
Acetoguanamine was placed into the lower everted lid of one eye of each animal. The eyelids were then gently held together for one second before releasing. The contralateral eye remained untreated and served as a control.
Observation period (in vivo):
Examination of the eyes was made after 1 hour and 1, 2, 3, 4 and 7 days after instillation.
Number of animals or in vitro replicates:
three
Other effects:
The numerical scores awarded to the ocular reactions elicited by Acetoguanamine, are given in Table 1.
A corneal opacity developed in one animal 24 h after instillation and was still visible 4 d following instillation. The opacity had resolved 7 days after instillation.
No iridial inflammation was seen throughtout oberservation period.
A diffuse crimson-red colouration of the conjunctivae was observed, 1 h after instillation only, in all three animals.
All conjuctival reactions had resolved 24 or 48 h after instillation.

TABLE 1: Ocular reactions elicited by Acetoguanamine.

Rabbit Number and Sex

Bodyweight

(Day 1)

Region of Eye

One hour

Day after instillation

1

2

3

4

7

812

female

2980 g

Corea

Density

0

0

0

0

0

0

Area

0

0

0

0

0

0

Iris

0

0

0

0

0

0

Conjunctivae

Redness

2

0

0

0

0

0

Chemosis

1

0

0

0

0

0

838

female

2870 g

Corea

Density

0

0

0

0

0

0

Area

0

0

0

0

0

0

Iris

0

0

0

0

0

0

Conjunctivae

Redness

2

0

0

0

0

0

Chemosis

1

0

0

0

0

0

839

female

3000 g

Corea

Density

0

2

1

1

1

0

Area

0

1

1

1

1

0

Iris

0

0

0

0

0

0

Conjunctivae

Redness

2

1

0

0

0

0

Chemosis

1

1

0

0

0

0

SCORING SYSTEM:

Cornea:

Opacity: degree of density (area most dense taken from reading)

0       No ulceration or opacity

1       Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible

2       Easily discernible translucent areas, details of iris slightly obscured

3       Nacrous areas, no details of iris visible, size of pupil barely discernible

4       Opaque cornea, iris not discernible through the opacity

Area of cornea involved:

1       One quarter (or less) but not zero

2       Greater than one quarter, but less then half

3      Greater than half, but less than three quarters

4       Greater than three quarters, up to whole area

Iris:

0       Normal

1       Markedly depened rugae, congestion, swelling, moderate circumcorneal hyperaemia or injection, any of these or combination              of any thereof, iris still reacting to light (sluggish reaction is positive)

2       No reaction to light, haemorrhage, gross destruction (any or all of these)

Conjunctivae:

Redness (refers to palpebral and bulbar conjunctivae cornea and iris)

0       Blood vessels normal

1       Some blood vessels definitely hyperaemic (injected)

2       Diffuse, crimson colour, individual vessels not easily discernible

3       Diffuse, beefy red

Chemosis (lids and/or nictitating membranes)

0       No swelling

1       Any swelling above normal (includes nictitating membranes)

2       Obvious swelling with partial eversion of lids

3       Swelling with lids about half-closed

4      Swelling with lids more than half-closed

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Acetoguanamine elicites transient, corneal opacification and temporary well-defined conjuctival reactions. Nevertheless this effects do not lead to a classification of the test substance.
Executive summary:

In an eye irritation study according to OECD 405 approx. 85 mg of Acetoguanamine, the weight occupying a volume of 0.1 mL was placed into the lower lid of one eye of each of the test animals (three adult New Zealand White rabbits). Examination of the eyes was made after 1 hour, and 1, 2, 3, 4 and 7 days after instillation. Irritation was scored and it was determined that Acetoguanamine elicites only transient, corneal opacification and temporary well-defined conjuctival reactions. Nevertheless this effects do not lead to a classification of the test substance.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In an acute skin irritation/corrosion study Acetoguanamine did not show any irritating effects on the intact skin after a contact time of 4 hours. Further no skin reactions were recorded throughout the observation period of 4 days.

In an acute eye irritation study Acetoguanamine elicited transient corneal opacification in one animal and a transcient but well-defined conjunctival reaction in all three animals. Nevertheless this was not relevant for classification.

Justification for classification or non-classification

Acetoguanamine is neither irritating/corrosive to the skin nor irritating to the eyes based on the results of appropriate guideline studies.