Registration Dossier

Administrative data

Description of key information

Skin irritation:

The in vitro skin irritation test in the EPISKIN model with cadmium telluride (Kiss, CiToxLAB Hungary 2012) indicates that the test item is Non Irritant (NI).

In the acute skin irritation study performed with CdTe in New Zealand White rabbits (Zelenak, CiToxLAB Hungary 2012), the irritancy of the test item was evaluated according to the Draize method (OECD No.: 404, 2002). The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for erythema were 0.33, 0.00 and 0.00 respectively.

The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for oedema were 0.00, 0.00 and 0.00 respectively.

Eye irritation:

The in vitro eye irritation study in the Isolated Chicken Eyes model with cadmium telluride (Kiss, CiToxLAB Hungary 2011) suggests that the test item is not irritating. According to the guideline OECD 438, cadmium telluride does not require a classification as a severe eye irritant. Cadmium telluride remained adhered to the cornea surface after the post-treatment rinse. An in vivo study is required for classification.

In the acute eye irritation study performed with CdTe in New Zealand White rabbits (Török-Bathó, CiToxLAB Hungary 2012), the irritation effects of the test item were evaluated according to the Draize method (OECD No.: 405, 2002).Cadmiumtelluride applied to rabbits’ eye mucosa, caused significant conjunctival irritant effects at one hour which were reduced at 24 hours after application. The effects were fully reversible within 72 hours.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: S&K-LAP Kft. 2173 Kartal, Császár út 135, HUNGARY
- Age at study initiation: ~12 weeks old
- Weight at study initiation: 3075-3323 g
- Housing: Rabbits were individually housed in AAALAC approved metal wire rabbit cages (65x65 cm with height of 45 cm). Cages were of an open wire structure and cages were placed together to allow some social interaction with rabbit(s) in adjoining cages.
- Diet: Animals received PURINA Base – Lap gr. diet for rabbits produced by AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi út, Hungary, ad libitum
- Water: municipal tap water, as for human consumption, ad libitum, from an automatic system.
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.1-19.0 °C
- Humidity (%): 24-60%
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5g
Duration of treatment / exposure:
4 hours
Observation period:
72h
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: approximately 6 cm² area of intact skin

REMOVAL OF TEST SUBSTANCE
- Washing: the remaining test item was removed with water at body temperature
- Time after start of exposure: After 4 hours

SCORING SYSTEM:

The dermal irritation scores were evaluated according to the scoring system by Draize (1959)

SCORING SYSTEM OF ERYTHEMA AND OEDEMA FORMATION

Erythema and eschar formation

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

Maximum possible erythema score: 4

Oedema formation

No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of it will be well defined
by definite raising) 2
Moderate oedema (raised appr. 1 mm) 3
Severe oedema (raised more than 1 mm and extending
beyond area of exp.) 4

Maximum possible oedema score: 4



Irritation parameter:
erythema score
Basis:
mean
Remarks:
animals #1, #2, #3
Time point:
other: 1h
Score:
1.33
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animals #1, #2, #3
Time point:
24 h
Score:
0.33
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animals #1, #2, #3
Time point:
48 h
Score:
0
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animals #1, #2, #3
Time point:
72 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal)
Time point:
24/48/72 h
Score:
0.33
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal)
Time point:
24/48/72 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal)
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
mean
Remarks:
animals #1, #2, #3
Time point:
other: 1h
Score:
1
Irritation parameter:
edema score
Basis:
mean
Remarks:
animals #1, #2, #3
Time point:
24 h
Score:
0
Irritation parameter:
edema score
Basis:
mean
Remarks:
animals #1, #2, #3
Time point:
48 h
Score:
0
Irritation parameter:
edema score
Basis:
mean
Remarks:
animals #1, #2, #3
Time point:
72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal)
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal)
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal)
Time point:
24/48/72 h
Score:
0
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
24/48/72 h
Score:
0.11
Other effects:
MORTALITY : no mortality observed during the study.
BODY WEIGHTS: no effect of treatment on body weight.
CLINICAL OBSERVATION

General Daily Examination: no treatment-related clinical signs noted.

Examination of Skin-Irritancy:

At observation one hour after patch removal:
well defined erythema (score2) was noted in one animal, very slight erythema (score 1) was observed in two animals and very slight oedema (score 1) was noted in all animals. The test item was also staining on the hair and skin in all animals.

At observation 24 hours after patch removal:
very slight erythema (score 1) was observed in one animal and the test item was staining on the hair and skin in all animals.

At observation 48 and 72 hours after patch removal:
there were no observed clinical signs noted on the skin of the treated animals

As no clinical signs were observed the study was terminated after the 72 hours observation.

The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for erythema were 0.33, 0.00 and 0.00 respectively.

The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for oedema were 0.00, 0.00 and 0.00 respectively.

The Primary Irritation Index (considering readings at 24, 48 and 72 hours after patch removal) was calculated as 0.11.

SCORING OF ERYTHEMA FORMATION

 

 

TABLE 1

 

Animal No./
Sex

Body weight (g)

1 h

24 h

48 h

72 h

at the beginning
of the study

at the end
of the study

00141/ M

3323

3380

2

1

0

0

00123/M

3120

3172

1

0

0

0

00149/M

3075

3144

1

0

0

0

TOTAL

-

-

4

1

0

0

MEAN

-

-

1.33

0.33

0

0

       

 

 

 

SCORING OF OEDEMA FORMATION

 

 

TABLE 2

 

Animal No./
Sex

Body weight (g)

1 h

24 h

48 h

72 h

at the beginning
of the study

at the end
of the study

00141/ M

3323

3380

1

0

0

0

00123/M

3120

3172

1

0

0

0

00149/M

3075

3144

1

0

0

0

TOTAL

-

-

3

0

0

0

MEAN

-

-

1

0

0

0

 

 

M   = male

d     = day

h     = hour



 

MEAN VALUES OF SKIN IRRITATION SCORES

(24, 48, 72 hours reading)

 

TABLE 3

 

 

Animal Number

Sex

Erythema

Oedema

00141

male

0.33

0.00

00123

male

0.00

0.00

00149

male

0.00

0.00

 

 


 

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to the UN Globally Harmonised System of Classification and Labelling of Chemicals,Cadmium telluride does not require classification as a skin irritant.

 
Executive summary:

An acute skin irritation study was performed with Cadmium telluride in New Zealand White rabbits. Parameters monitored during this study included mortality, body weight measurements and clinical observations. The irritancy of the test item was evaluated according to the Draize method (OECD No.: 404, 2002).

A weight of 0.5g granules test item was applied to the skin of the experimental animals as ground to a powder. The test item was applied as a single dose. Sufficient water to damp the material was used to ensure good contact with the skin and an adhesive clear plastic patch was applied. The trunk was wrapped in clear plastic with medical tubing used to hold the patch in place. The untreated skin of each animal served as control.

After 4 hours, the remaining test item was removed with water at body temperature.

 

To assess skin irritation, animals were examined at 1, 24, 48 and 72 hours after the patch removal. Additional general examinations were performed daily.

There was no mortality or systemic clinical changes related to Cadmium telluride administration.

There was no effect of treatment on body weight.

 

At observation one hour after patch removal,well defined erythema (score2) was noted in one animal, very slight erythema (score 1) was observed in two animals and very slight oedema (score 1) was noted in all animals.The test item was also staining on the hair and skin in all animals.

 

At observation 24 hours after patch removal,very slight erythema (score 1) was observed in one animal and the test item was staining on the hair and skin in all animals.

 

At observation 48 and 72 hours after patch removal,there were no observed clinical signs noted on the skin of the treated animals

 

As no clinical signs were observed the study was terminated after the 72 hours observation.

The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for erythema were 0.33, 0.00 and 0.00 respectively.

The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for oedema were 0.00, 0.00 and 0.00 respectively.

 

The Primary Irritation Index (considering readings at 24, 48 and 72 hours after patch removal) was calculated as 0.11.

 

According to Directive 2001/59/EC,Cadmium telluride does not require classification as a skin irritant.

 

According to the UN Globally Harmonised System of Classification and Labelling of Chemicals,Cadmium telluride does not require classification as a skin irritant.

 

According to the classification system based on the scheme devised by Draize (1959),Cadmium telluride is a "mild irritant".

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: S&K-LAP Kft. 2173 Kartal, Császár út 135, HUNGARY
- Age at study initiation: ~13 weeks old
- Weight at study initiation: 3232 – 3500 g
- Housing: Rabbits were individually housed in AAALAC approved metal wire rabbit cages. Cages were of an open wire structure and cages were placed together to allow some social interaction with rabbit(s) in adjoining cages
- Diet: Animal received PURINA Base – Lap gr. diet for rabbits produced by AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi road, Hungary, ad libitum.
- Water: municipal tap water, as for human consumption, ad libitum, from an automatic system.
- Acclimation period: 20 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.1- 21.4°C
- Humidity (%): 24 - 60 %
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 100mg


Duration of treatment / exposure:
1 hour
Observation period (in vivo):
The eyes were examined at 1, 24, 48 and 72 hours after treatment. The study was terminated after 72 hours observation.
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): eyes of the test animals were washed out
- Time after start of exposure: at 1 hour after application of test item

SCORING SYSTEM:
The eye irritation scores were evaluated according to the scoring system by Draize (1977) and OECD 405 (24 April 2002)

Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal)
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal)
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal)
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Remarks:
animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal)
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Remarks:
animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal)
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Remarks:
animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal)
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
other: discharge
Basis:
animal #1
Remarks:
animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal)
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
other: discharge
Basis:
animal #2
Remarks:
animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal)
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
other: discharge
Basis:
animal #3
Remarks:
animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal)
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation

MORTALITY: no mortality observed during the study.

BODY WEIGHTS: The body weight and body weight change were considered to be normal with no indication of treatment related effect

CLINICAL OBSERVATION:

General daily examination: no clinical signs observed that could be related to treatment.

Examination of eye-irritancy:

The eyes were examined at 1, 24, 48 and 72 hours after the application.

 

Initial Pain Reaction(IPR) (score 1) was observed in the animals.

One hour after the application:Conjunctival redness (score 1) and discharge (score 1 or 3) was noted in 2/3 animals.

At 24 hours after treatment:Conjunctival redness (score 1) was noted in one animal and discharge (score 1) was noted in 2/3 animals.

At 48 hours after treatment:Conjunctival redness (score 1) and discharge (score 1) was noted in one animal.

At 72 hours after treatment:There were no clinical signs, and noconjunctival orcorneal effects observed.

 

As there were no clinical signs observed, the study was terminated 72 hours after the treatment.

During the study, the control eye of each animal was symptom-free.


The general state and behavior of animals were normal throughout the study period.

 There were no notable body weight changes during the study period.

 The animal’s individual mean scores (considering readings at 24, 48 and 72 hours after the treatment) were as follows:

chemosis          : 0.00, 0.00, 0.00

discharge         : 0.00, 0.33, 0.67

redness             : 0.00, 0.67, 0.00

cornea opacity : 0.00, 0.00, 0.00

iris                    : 0.00, 0.00, 0.00

TABLE 1:Individual Scores for Ocular Irritation

 

Abbreviations:   R    = Redness                                OD =   Opacity degree of density

                               CH = Chemosis                              OE =   Extent of opaque area

D    = Discharge                              IPR=   Initial pain reaction

 

Time

Animal No.

Score of irritation

IPR

Conjunctivae

Opacity of cornea

Iris

Control eye

Other sign

R

CH

D

OD

OE

R

1 hour

00124

1

0

0

0

0

0

0

-

1

00182

1

0

3

0

0

0

0

-

1

00122

0

0

1

0

0

0

0

-

1

Time of Observation: Day 0

Time

Animal No.

Score of irritation

Conjunctivae

Opacity of cornea

Iris

Control eye

Other sign

R

CH

D

OD

OE

R

24 hours

00124

0

0

0

0

0

0

0

-

00182

1

0

1

0

0

0

0

-

00122

0

0

1

0

0

0

0

-

Time of Observation: Day 1

Time

Animal No.

Score of irritation

Conjunctivae

Opacity of cornea

Iris

Control eye

Other sign

R

CH

D

OD

OE

R

48 hours

00124

0

0

0

0

0

0

0

-

00182

1

0

0

0

0

0

0

-

00122

0

0

1

0

0

0

0

-

Time of Observation: Day 2

Time

Animal No.

Score of irritation

Conjunctivae

Opacity of cornea

Iris

Control eye

Other sign

R

CH

D

OD

OE

R

72 hours

00124

0

0

0

0

0

0

0

-

00182

0

0

0

0

0

0

0

-

00122

0

0

0

0

0

0

0

-

Time of Observation: Day 3

TABLE 2: MEAN VALUES OF EYE IRRITATION (24, 48, 72 hour reading)

 

 

Animal Number

Sex

Cornea Opacity

Iris

Conjunctivae

Redness

Chemosis

Discharge

00124

male

0.00

0.00

0.00

0.00

0.00

00182

male

0.00

0.00

0.67

0.00

0.33

00122

male

0.00

0.00

0.00

0.00

0.67

TABLE 3: BODY WEIGHT DATA

 

 

 

Animal Number

Beginning of study
(g)

At the end of study
(g)

Body weight gain
(g)

00124

3500

3551

51

00182

3232

3279

47

00122

3337

3380

43

 

 

 

 

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item Cadmium telluride, applied to rabbit eye mucosa, caused significant conjunctival irritant effects at one hour which were reduced at 24 hours after application. The effects were fully reversible within 72 hours.

According to Regulation (EC) No 1272/2008, Cadmium telluride does not require classification as an eye irritant.

Executive summary:

An acute eye irritation study of the test item Cadmium telluride was performed in New Zealand White rabbits. The irritation effects of the test item were evaluated according to the Draize method (OECD No.: 405, 2002).

The test item was placed into the conjunctival sac of the left eye of each animal. The untreated right eye served as control. An amount of 0.1g of the test item was administered as a single dose.

 

The eyes were examined at 1, 24, 48 and 72 hours after the application.

 

Initial Pain Reaction(IPR) (score 1) was observed in the animals.

One hour after the application:Conjunctival redness (score 1) and discharge (score 1 or 3) was noted in 2/3 animals.

At 24 hours after treatment:Conjunctival redness (score 1) was noted in one animal and discharge (score 1) was noted in 2/3 animals.

At 48 hours after treatment:Conjunctival redness (score 1) and discharge (score 1) was noted in one animal.

At 72 hours after treatment:There were no clinical signs, and noconjunctival orcorneal effects observed.

 

As there were no clinical signs observed, the study was terminated 72 hours after the treatment.

During the study, the control eye of each animal was symptom-free.

The general state and behavior of animals were normal throughout the study period.

There were no notable body weight changes during the study period.

 

The animal’s individual mean scores (considering readings at 24, 48 and 72 hours after the treatment) were as follows:

chemosis          : 0.00, 0.00, 0.00

discharge         : 0.00, 0.33, 0.67

redness             : 0.00, 0.67, 0.00

cornea opacity : 0.00, 0.00, 0.00

iris                    : 0.00, 0.00, 0.00


 

The test item Cadmium telluride, applied to rabbit eye mucosa, caused significant conjunctival irritant effects at one hour which were reduced at 24 hours after application. The effects were fully reversible within 72 hours.

 

According toRegulation (EC) No 1272/2008,Cadmium telluride does not require classification as an eye irritant.


 

 

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Based upon the in vivo skin irritation data and according to Regulation (EC) No 1272/2008, cadmium telluride does not require classification as a skin irritant.

Based upon the in vivo eye irritation data and according to Regulation (EC) No 1272/2008, cadmium telluride does not require classification as an eye irritant.