Registration Dossier

Administrative data

Description of key information

Evaluation in an in vivo acute dermal irritation/corrosion test in rabbits found the test substance to be corrosive after 3-minutes of exposure as after exposure severe signs of irritation were observed and necrosis was noted on day 8.
An in vivo acute eye irritation/corrosion tests performed in rabbits the test substance elicited positive corneal, iridial and conjunctival responses in all eyes at 1 and 24h. Because of the severe nature of the responses and following a veterinary inspection the rabbits were humanely sacrificed following the 24h reading.

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:
18 Nov - 25 Nov 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: No full product composition given
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Breeder: Elevage Cunicole de Val de Selle, 80160 Prouzel, France.
Number of animals: One male New Zealand White rabbit was used.
Acclimation: at least 5 days before the beginning of the study.
Weight: on the day of treatment, the animal had a body weight 2.5 kg.
Identification: individual metal ear tag.
Environmental conditions: under continuous control and recording.
. temperature: 18±3°C
. relative humidity: 30 to 70%
. lightldark cycle: 12 h/12 h
. ventilation: approximately 12 cycles/hour of filtered, non-recycled air.
The animal was housed individually in polystyrene cage (48.2 cm x 58 cm x 36.5 cm).
The cage was equipped with a food container and a water bottle.
During the study, the animal had free access to 112 C pelleted diet (UAR, 91360 Villemoissonsur-Orge, France).
Each batch of food is analysed by the supplier for composition and contaminant levels. (appendix to report)
Drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum.
Bacteriological and chemical analyses of water are performed regularly by external laboratories.

DEVIATION FORM PROTOCOL:
. the relative humidity recorded in the animal room was sometimes outside of the target ranges specified in the protocol.
This minor deviation was not considered to compromise the validity or integrity of the study.
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped using electric clippers
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 ml placed on a dry gauze pad, which was then applied to the right flank (application for 4 hours) or the left flank (application for 3 minutes) of the animal. The pad was held in place by adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.
Duration of treatment / exposure:
3 minutes and 4 hours
After removal of the dressing, any residual test substance was wiped off by means of a moistened gauze pad.
Observation period:
1 hour, 24, 48 and 72 hours after removal of the dressing.
When there was persistent cutaneous irritation after 72 hours, the observation period was extended to a maximum of 14 days (until day 15) in order to determine the progress of the lesions and their reversibility.
Number of animals:
1
Details on study design:
The untreated skin served as control.
Any change in the animal's behaviour was noted.
Irritation parameter:
erythema score
Basis:
mean
Remarks:
3 minute exposure
Time point:
other: 24, 48, and 72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks:
Score 4 on day 8 when killed for ethical reason.
Irritation parameter:
edema score
Basis:
mean
Remarks:
3 minute exposure
Time point:
other: 24, 48, and 72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks:
Score 4 on day 8 when killed for ethical reason.
Irritation parameter:
erythema score
Basis:
mean
Remarks:
4 hr exposure
Time point:
other: 24, 48, and 72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks:
Score 4 on day 8 when killed for ethical reason.
Irritation parameter:
edema score
Basis:
mean
Remarks:
4 hr exposure
Time point:
other: 24, 48, and 72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks:
Score 4 on day 8 when killed for ethical reason.
Irritant / corrosive response data:
After a 3-minute or 4-hour exposure, a moderate to severe erythema (grade 3 or 4) and a slight to severe oedema (grade 2 or 4) were observed between day 2 and day 8; crusts were recorded from day 3 or day 5 and cutaneous necrosis was noted on day 8. The animal was then killed on day 8 for ethical reason.
Mean scores over 24, 48 and 72 hours for the animal after a 4-hour exposure were 3.0 for erythema and 2.0 for oedema.
Other effects:
no data.

Scoring dermal irritation:

      1h 24h 48h 72h Mean        
  rabbit day 1 2 3 4 24/48/72 5 6 7 8
3 min #1 Erythema 2 3 3 3 3,0 4 4 4 4
  Oedema 0 2 2 2 2,0 2 2 2 4
    Other                  
4-hrs #1 Erythema 2 3 3 3 3,0 4 4 4 4
  Oedema 2 2 2 2 2,0 2 2 2 4
    Other     A A   A A A N

A = Crust

N = Necrosis

Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Remarks:
Migrated information
Conclusions:
Signs of necrosis became apparent after 8 days observation following 3 minutes exposure.
Therefore, the test substance STABIRAM MS6 is corrosive when applied topically to rabbits. GHS Cat. 1B.
Executive summary:

Stabiram MS6 was tested under GLP according to OECD 404.

0.5 ml was dermally applied to the clipped skin of one rabbits under semi-occusive conditions for 3 minutes and 4 hours. Following both exposure durations the mean score for erythema and edema at 24, 48 and 72 hours after patch removal were 3.0 for erythema and 2.0 for edema. Also following both exposures necrosis was noted on day 8.

Therefore Stabiram MS6 should be classified according to GHS as: Corrosive (Category 1B).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

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:
16 Mar - 23 Mar 1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: pre-GLP; Includes GLP-like QA statement.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Three New Zealand White strain rabbits in the weight range 2.5 to 3.1 kg, prior to treatment on Day 1 and approximately 11 to 14 weeks of age were
obtained from Froxfield Rabbits, Petersfield, Hampshire. The rabbits selected for the study were all acclimated to the laboratory environment.

The rabbits were individually housed in metal cages with perforated floors in Building R 14 Room 3. They had free access to tap water and SDS
Standard Rabbit Diet. Animal room temperature was maintained at approximately 19°C and relative humidity at 30-70%. Air exchange was
maintained at approximately 19 air changes per hour and lighting was controlled to give 12 hours of artificial light (0700-1900 hours) in each 24
hour period. All animals were observed daily for signs of ill health or toxic signs.
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
0.1 ml
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3
Details on study design:
The eyes of each animal were examined prior to instillation of the test substance to ensure that there was no pre-existing corneal damage or
conjunctival inflammation. A 0.1 ml aliquot of Redicote EN 611 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.

Examination of the eyes was made after 1 hour and 1, 2, 3, 4 and 7 days after instillation. Observation of the eyes was aided by the use of a hand held
torch.
Irritant / corrosive response data:
All three animals gave a "positive" response. Corneal opacification developed in all three animals and was still present seven days after instillation,
when vascularisation of the cornea was also seen in one animal. Iridial inflammation was observed in all three animals. A diffuse, crimson colouration of the conjuntivae accompanied by swelling with partial eversion of the eyelids or with the eyelids about half-closed was seen in all three animals.
A copious discharge was observed in all three animals. All three animals were killed on humane grounds, seven days after instillation, due to the
severity of the ocular reactions.

Summary of ocular lesions

Anim.

No.

Effect

Hours

Days after application

Mean

score cornea

Days

1/2/3

Mean score iritis

Days 1/2/3

Mean score redness Days 1/2/3

Mean score chemosis Days 1/2/3

1

1

2

3

4

7

1

Cornea

Iris

Redness

Chemosis

D

0

2

2

1

0

2

1

1

1

2

1

2

1

2

1

2

1

2

1

2

0K

1

1

1.33

0.67

2

1

2

Cornea

Iris

Redness

Chemosis

D

0

1

2

1

1

1

3

1

1

2

2

2

1

2

3

2

1

2

3

1

1K

2

2

1.33

1

1.67

2.67

3

Cornea

Iris

Redness

Chemosis

D

0

1

2

1

0

1

1

2

1

2

2

2

1

2

2

2

1

2

2

3V

1K

2

2

1.67

0.67

2

2

D Dulling of cornea

V Vascularization of cornea

K Killed

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Remarks:
Migrated information
Conclusions:
Instillation of Redicote EN 611 into the rabbit eye elicited a positive response in all of the three treated animals according to OECD test criteria.
Severe ocular reactions were observed including vascularization of the cornea. Based on the severity of the reactions, the test article should be
classified as corrosive under GHS.
Executive summary:

The study was conducted to asseses the irritation potential of Redicote EN 611 when instilled into the eyes of rabbits in accordance with OECD 405. 0.1 ml was instilled into one eye of three rabbits. Eye were evaluated 1 hour after instillation and again 1, 2, 3, 4 and 7 days later.

Instillation of Redicote EN 611 into the rabbit eye elicited a positive response in all of the three treated animals according to OECD test criteria. Severe ocular reactions were observed including vascularization of the cornea. Based on the severity of the reactions, the test article should be classified as corrosive under GHS.

Label requirements under GHS: Symbol "Corrosion"; Signal word "Danger"; Hazard statement "Causes serious eye damage"

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Diamine quaternised C16-18, C18 unsaturated, product is commonly marketed as an about 50% solution in water with organic solvent. Studies have been performed with commercial products.

 

Skin irritation/corrosion:

1.    Skin irritation (HRC, 87403D/AKZ 246/SE, 1987, OECD 404, QA statement): Irritating

2.    Skin irritation (CIT, 20193 TAL, 2000, OECD 404, GLP): Irritating

3.    Skin irritation (CIT, 20302 TAL, 2000, OECD 404, GLP): Corrosive

4.    Skin irritation (CIT, 19301 TAL, 2000, OECD 404, GLP): Corrosive

 

The skin irritation potential of N,N,N',N',N'-Pentamethyl-N-C16-18(even numbered)C18 unsatured-alkyl-1,3 propanediammonium chloride was determined in 4 studies performed according to the OECD 404 guideline, where 3 of the studies were performed under GLP conditions. While two of the studies only observed an irritating effect on skin, the remaining two studies demonstrated a corrosive effect. These differences are considered to reflect both the type of product tested, as the composition is not similar, and the amount of active ingredient. A worst case assumption of corrosive to skin is supported.

 

1. Substance tested:30-40% active; 10-15% CaCl2and 50-60% water. Four hour semi-occlusive application resulted to severe irritation. In one animal necrotic patches were noted.

 

2.Substance tested:54% active; 27% IPA and ca. 20% water.3-minutes exposure: A very slight or well-defined erythema (grade 1 or 2) was observed from day 1 up to day 7, then dryness of the skin, sometimes associated with crusts, was recorded from day 7 up to the end of the observation period (day 15). 4-hour exposure: Mean scores over 24, 48 and 72 hours for each animal were 3.0, 2.7 and 3.0 for erythema and 2.0, 1.3 and 1.7 for oedema. For two of the three animals not fully reversible within 15 days. Dryness of the skin from day 7 through to end.

 

3. Substance tested: 48.7% active; 27.6% water and ca. 24% IPA. One animal tested 3 minutes, resulted to slight to severe erythema (grades 1 to 4) and a very slight or slight oedema (grade 1 or 2) were observed from day 1 or day 2 up to day 10, the end of observation period. Not reversible: Erythema 4 at day 10, and crust & dryness observed on days 7 through 10.

4-hour exposure: Severe cutaneous reactions including a well-defined to severe erythema (grades 2 to 4), a very slight to severe oedema (grades 1 to 4), dryness of the skin and crusts were noted in all animals from day 1. Cutaneous necrosis was also recorded in one animal between day 3 and day 6.

 

4.Substance tested: 47.1% active; 28.1% water and ca. 25% IPA. 0.5 ml was dermally applied to the clipped skin of one rabbits under semi-occusive conditions for 3 minutes and 4 hours. Following both exposure durations the mean score for erythema and edema at 24, 48 and 72 hours after patch removal were 3.0 for erythema and 2.0 for edema. Also following both exposures necrosis was noted on day 8.

 

Eye Irritation / corrosion:

One pre-GLP study is recorded for this endpoint.

Substance tested: 30-40% active substance, with 10-15% CaCl2 and 50-60% water. 0.1 ml was

instilled into one eye of three rabbits in accordance with OECD 405. Corneal opacification developed in all three animals and was still present seven days after instillation, when vascularisation of the cornea was also seen in one animal. Iridial inflammation was observed in all three animals. A diffuse, crimson colouration of the conjuntivae accompanied by swelling with partial eversion of the eyelids or with the eyelids about half-closed was seen in all three animals.

A copious discharge was observed in all three animals. All three animals were killed on humane grounds, seven days after instillation, due to the severity of the ocular reactions.


Justification for selection of skin irritation / corrosion endpoint:
Study of highest quality and validity.

Justification for selection of eye irritation endpoint:
Only study available and of adequate reliability.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

Skin Irritation:

In thein vivodermal corrosion study in rabbits, severe signs of irritation were observed after 3-minute exposures and necrosis was noted on day 8. Consequently, GHS classification 1B is appropriate, with hazard statement H314: Causes severe skin burns and eye damage.

 

Eye Irritation:

According to the results of the available study, the substance must be considered as highly irritating for eyes and warrants a classification in category 1, eye damage.Under GHS with the hazard phrase ‘H314 Causes severe skin burns and eye damage’ additional classification for eyes is not necessary.

 

Respiratory tract irritation:

There is no information is available following exposure via inhalation. The substance is a paste with a very low vapourpressure.Due to its physical state and physical chemical properties, it is unlikely that it will form inhalable dust, mist or fumes limiting the possible extend of exposure via inhalation. Inhalation of aerosols may cause respiratory irritation due to the corrosive properties of the substance.

For STOT-SE Cat 3 Respiratory Tract Irritation (RTI): Although the substance is very corrosive substances, the low vapour pressure prohibits occurrence of respiratory irritation by vapour. The classification of corrosive is already considered to implicitly cover the potential of RTI and additional Cat.3 is considered to be superfluous (Guidance CLP Ch. 3.8.2.5)