Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
2 May 1990 - 13 June 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: study performed similar to standard guideline and under GLP. There is no CoA avaialble for the test substance.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
Extra exposure periods were added; 3-minute, 1-hour, and 4-hour applications.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
Description : opaque, darkplum-coloured, slightly viscous liquid
Container : glass screw-top bottle
Label: CATIMULS 404
Reference: 16085
Storage conditions: room temperature

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., England
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.22-2.50 kg
- Housing: individuall y housed in suspended metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: minimal 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-23
- Humidity (%): 60-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: No data

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): 0.5ml
Duration of treatment / exposure:
3-minute, 1-hour, and 4-hour applications
Observation period:
3-minute: 7 days
1-hour: 7 days
4-hour: 14 days
Number of animals:
3-minute: 6 animals
1-hour: 6 animals (same as for 3 min exposure)
4-hour: 3 animals
Details on study design:
TEST SITE
- Area of exposure: flanks, for 3 minutes the left flank was exposed, 7 days later for 1 hour left flank was exposed of the same animals. 3 new animals were used for the 4 hour exposure and the left flank was exposed.
- % coverage: 2.5 x 2.5 cm guaze patches
- Type of wrap if used:
The patch was secured in position over the test material with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 cm x 4.0 cm). The trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: after 3 minutes, 1 hour of 4 hours.


SCORING SYSTEM: according to draize (Draize J.H. (1959) Association of Food and Drug Officials of the United States, Austin, Texas,
"The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics")
EVALUATION OF SKIN REACTIONS
Erythema and Eschar Formation Value
No erythema ........................................................ . 0
Very slight erythema (barely perceptible) 1
Well -defined erythema ........................................ 2
Moderate to severe erythema 3
Severe erythema (beet 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
millimetre) ..................................................... 3
Severe oedema (raised more than 1 millimetre
ending beyond the area of exposure) 4

Results and discussion

In vivo

Results
Time point:
other: 14 days
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: 4 hour exposure: on day 14 scoring was not possible due to the corrosive effecst of the test substance
Irritant / corrosive response data:
3 minute exposure
Incidents of very slight erythema were noted up to 72 hours after patch removal. Desquamation was noted at one treated skin site. No other adverse
dermal reactions were observed. No corrosive effects were noted.

1 hour exposure
Well-defined erythema was noted at all treated skin sites one hour after patch removal. Haemorrhage of the dermal capil laries was aso commonly
noted. On occasions the reactions extended beyond the site of application. Well-defined or moderate to severe erythema persisted at all treated skin
sites up to the 72-hour observation. Other adverse reactions commonly noted at these times were light brown discolouration of the epidermis and
haemorrhage of the dermal capillaries. The reactions extended beyond the site of application in two animals.
One animal was found dead on day 4 of the test. This was not treatment related and did not affect the integrity of the study. The remaining animals all showed hyperkeratinisation when observed on day 7. One animal also showed signs of reduced re-growth of fur at this time. Slight to severe oedema was observed at all treated skin sites one hour after patch removal. The oedema dropped ventrally below the treatment site in one animal. Slight to severe oedema was observed at the 24-hour observation and slight to moderate oedema persisted at all treatment sites up to 72 hours after patch removal. No oedema formation was observed in the remaining animals on day 7. No corrosive effects were noted.

4 hour exposure
Severe erythema and green-coloured necrosis was noted at all treated skin sites one hour after patch removal. Well-defined er,ythema surrounded the scabs and two treatment sites showed haemorrhage of the dermal capillaries. These reactions persisted at the 24-hour observation.

At the 48-hour observation and for the duration of the study it was not possible to evaluate the erythema due to the other adverse dermal effects. These included hardened dark brown/black-coloured or undulating scabs, light brown discolouration of the epidermis, blanching, well -defined or moderate erythema surrounding the scabs, desquamation, hyperkeratinisation, scabs, lifting to reveal further deep scabbing and scar tissue.

Severe oedema was noted one and 24 hours after patch removal. At the 48-hour observation it was not possible to evaluate the oedema at two treatment sites due to the degree of thickening. The remaining treatment site showed moderate oedema at this time and at the 72-hour observation. On days 7 and 14 it was not possible to evaluate the oedema at any treated skin site. On occasions during the study the oedema was observed to extend beyond the site of application.

The dermal responses seen in all three animals were considered to be indicative of corrosion.

Any other information on results incl. tables

Legenda

N = green-coloured necrosis

Me = moderate erythema surrounding scab

We = well-defined erythema surrounding scabs

Hy = hyperkeratinisation

?e = evaluation of erythema not possible due to adverse dermal reactions

St = hardened dark brown/black-coloured scabs

Sw = undulating scab

B7 = blanching

D = desquamation

Sd = scab lifting to reveal further deep scabbing

?Od = degree of thickening precluded evaluation of oedema

R = reactions extends beyond treatment site

Hd = haemorrhage of the dermal capillaries

Br = light brown discolouration of the epidermis

Sc = scar tissue

Fr = reduced re-growth of fur

Oe = oedema drops ventrally below treatment site

* = animal found dead on day 4 of the study

3 minute exposure

Skin Reaction  Reading (Hours)                 Individual score - Rabbit No. and Sex
     97 115  119  123  129  130 
     Male Male  Female  Male  Male  Male 
 Erythema/eschar formation  1  0 1
   24
   48
   72 0 1D 
   7 days 0D 
 oedema formation  1 0  0 0 0  
   24
   48 0
   72 0 0
    7 days  

1 hour exposure

Skin Reaction  Reading (Hours)                 Individual score - Rabbit No. and Sex
     97 115  119  123  129  130 
     Male Male  Female  Male  Male  Male 
 Erythema/eschar formation  1  2Hd  2RHd  2RHd  2Hd  2R  2Hd
   24  3HdBr  2HdBr  2HdBrR  2HdBr  2R  2Hd  
   48  3Br  2Br 2HdBrR  2Br  2R  2Hd
   72  3Br  2Br  2BrR  2Br  2R 2Br
   7 days  0Hy  0Hy  0HyFr  0Hy  0Hy  *
 oedema formation  1  4 4 3  30e  2  2  
   24  4 3  3  2  2
   48  3 3  3  3  2
   72  2 3 3  3  3  2
    7 days  0  0  0  0  0  *

4 hour exposure

Skin Reaction  Reading (Hours)                 Individual score - Rabbit No. and Sex
     24 35 48  
     Female Male  Male 
 Erythema/eschar formation  1  4NWe  4NhdWe  4NhdWe      
   24  4NWe  4NhdWe  4NhdWe      
   48  ?eStSwWe  ?eStBrBlMe  ?eStSwWe      
   72  ?eStSwWeBl  ?eStSwBrBlMe  ?eStSwWeBl      
   7 days  ?eStSwD  ?eStSwHy  ?eStSw      
 14 days  ?eSdD  ?eScD  ?eSdD        
 oedema formation 1  4  4      
   24  4R 4R  4      
   48  ?0d  3R  ?0d      
   72  ?0d  3R  ?0d      
    7 days  ?0d  ?0d  ?0d      
   14 days  ?0d  ?0d  ?0d      

Applicant's summary and conclusion

Interpretation of results:
Category 1C (corrosive) based on GHS criteria
Remarks:
Migrated information
Conclusions:
The test material produced evidence of visible necrosis following an exposure period of up to four hours and no recovery was observed within 14 days. Based on this study the test substance should be regarded as corrosive to skin. The symbol "C" and risk phrase R 34 "CAUSES BURNS" are therefore required.
Executive summary:

The study was based on the recommendations of the OECD Guidelines for Testing of Chemicals (1981) No. 404 "Acute Dermal Irritation/Corrosion" and performed under GLP. In total 9 new zealand white rabbits were dermally exposed under semi-occlusion to 0.5ml of the undiluted test substance. 6 rabbits were first exposed for 3 minutes on their left flank, 7 days later the same animals were exposed on their right flank for 1 hour. The other three animals were exposed for 4 hours on their left flank. After exposure the test substance was removed by gentle swabbing with cotton wool soaked in distilled water. Obervations were made at 1 , 24, 48 72 hours and after 7 days. The animals exposed for 4 hours were observed up to 14 days. After 3 minutes exposure slight effects were observed and these were reversible after 7 days. Irritation was observed after the 1 hour exposure and these effects were not revesible within 7 days. The test material produced evidence of visible necrosis following an exposure period of up to four hours and no rceovery was observed within 14 days. Based on this study the test substance should be regarded as corrosive to skin. The symbol "C" and risk phrase R 34 "CAUSES BURNS" are therefore required.

This study on Tall oil, reaction products with tetraethylenepentamine is valid for the evaluation of AAI substances for which higher ethyleneamines were used such as Tall oil fatty acids, reaction products with polyethylenepolyamines (Amidoamine/Imidazoline).

All substances within the AAI group show the same reactive groups, show similar composition of amide, imidazoline, and some dimer structures of both, with the length of original EA amines used for production as biggest difference. Inherent reactivity and toxicity is not expected to differ much between these substances.

As all in vivo skin irritation/corrosion studies performed on AAI substances all indicate them to be corrosive following 4 hour exposure, there seems to be no big difference in response with the variation on EA length used for the production of the AAI. Consequently, similar results can be expected forTall oil fatty acids, reaction products with polyethylenepolyamines (Amidoamine/Imidazoline).