Registration Dossier

Administrative data

Description of key information

Irritation:
- skin: not irritating (rabbit)
- eye: risk of serious damage to eyes (rabbit)

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:
05.07.1988 - 29.08.1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment.
Qualifier:
according to
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazleton Research Animals Inc., Denver, Pennsylvania.
- Age at study initiation: young adults (at least 8 weeks old)
- Weight at study initiation: no data
- Housing: individually
- Diet: Lab Rabbit Chow HF (Purina #5326), 125 g/day while on test.
- Water: tap water, ad libitum.
- Acclimation period: 55 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 21 °C
- Humidity (%): 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12 h / 12 h
Type of coverage:
semiocclusive
Preparation of test site:
other: closely clipped
Vehicle:
physiological saline
Controls:
other: untreated skin of the same animals served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 x 0.5 grams

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.25 ml
Duration of treatment / exposure:
4 h
Observation period:
3 days
Number of animals:
6 (2 males, 4 females).
Details on study design:
TEST SITE
- Type of wrap if used: gauze and porous tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): excess test material was removed using dry gauze.
- Time after start of exposure: 4 h

SCORING SYSTEM: draize score
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 h - 48 - 72 h
Score:
0.1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 h - 48 h - 72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects

Erythema findings: right front/left front:

 Time  animal 1  animal 2  animal 3  animal 4  animal 5 animal 6
 0,5 h  1/0 0/1   0/0  0/1  0/0  0/0
 24 h  0/1  0/0  0/0  0/1  0/0  0/0
 48 h  1/1  0/0  0/0  0/1  0/0  0/0
 72 h  0/0  0/0  0/0  0/0  0/0  0/0

Edema findings: right front/left front:

 Time  animal 1  animal 2  animal 3  animal 4  animal 5 animal 6
 0,5 h  0/0   0/0  0/0    0/0   0/0   0/0
 24 h   0/0   0/0   0/0   0/0   0/0  0/0
 48 h   0/0   0/0   0/0   0/0  0/0   0/0
 72 h   0/0   0/0   0/0  0/0   0/0   0/0

The test substance produced only mild to transient dermal irritation. The only irritation seen was slight (barely perceptible) erythema in three of the six animals, which subsided within one to three days.

Interpretation of results:
not irritating
Remarks:
Migrated information
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:
30.08.1988 - 27.09.1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment.
Qualifier:
according to
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hazleton-Dutchland Inc., Denver, Pennsylvania.
- Age at study initiation: young adults (at least 8 weeks old)
- Weight at study initiation: no data
- Housing: individually
- Diet: Lab Rabbit Chow HF (Purina #5326), 125 g/day while on test.
- Water: tap water, ad libitum.
- Acclimation period: 56 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 21 °C
- Humidity (%): 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12 h / 12 h
Vehicle:
unchanged (no vehicle)
Controls:
other: the adjacent eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1 cm3
Duration of treatment / exposure:
Single application, eyes were not washed after treatment.
Observation period (in vivo):
28 days
Number of animals or in vitro replicates:
6 (3 males and 3 females)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): No wash was performed after application of the material. Approximately 24 h after application, the treated eyes were rinsed to remove any residual test application.

SCORING SYSTEM: draize score

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24 h - 48 h - 72 h
Score:
1.3
Max. score:
4
Reversibility:
not fully reversible within: 28 days
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24 h - 48 h - 72 h
Score:
1.1
Max. score:
2
Reversibility:
fully reversible within: 28 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24 h - 48 h - 72 h
Score:
2.7
Max. score:
3
Reversibility:
not fully reversible within: 28 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24 h - 48 h - 72 h
Score:
2.4
Max. score:
4
Reversibility:
not fully reversible within: 28 days

Findings animals 1/2/3/4/5/6 (undiluted test substance):

 Time   Opacity Iritis   Conjunctival  Erythema  Conjunctival Chemosis                  
1 h +/+/+/0/+/+ +/0/+/+/0/+ 2/1/1/1/1/1 0/0/0/0/0/1                  
24 h 2/1/2/2/2/2 1/1/1/1/1/1 3/3/3/3/3/3 3/3/3/3/3/3                  
48 h

2/+/2/1/2/2

2/1/1/1/1/1 3/3/3/2/2/3 3/2/3/2/2/2                  
72 h 2/+/1/+/+/+ 2/1/1/1/+/1 3/2/3/2/2/2 2/2/2/2/2/2                  
 7 d 2/+/1/2/+/1 2/1/1/1/0/+ 2/2/2/2/1/2 1/1/2/1/1/1                  
14 d 2/+/2/1/0/0 2/1/1/0/0/0 2/2/1/2/2/1 2/1/1/1/0/0                  
 28 d  2/+/2/2/0/0  0/0/0/0/0/0 1/1/1/1/0/0  1/0/0/1/0/0                   

The test substance caused serious damage to eyes. All six animals exhibited severe conjunctival irritation (redness, chemosis, discharge, necrosis), corneal opacity, ulceration and iridial damage. All six animals also exhibited pannus (neovascularization of the corneal surface) one or more times between days 7 and 28. On day 7 one animal had an enlarged blood vessel on the anterior surface of the iris. Two animals had a fluid filled blister on the corneal surface on day 21 and/or 28. Three animals were noted to have hair loss around the eye. All six animals continued to exhibit severe irritation at termination of the study (day 28).

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Classification: risk of serious damage to eyes
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation:

In the key study (BIO/DYNAMICS, 1998; Validity 2) performed according to EPA-guideline OPP 81-5 (Acute Dermal Irritation) and GLP, the potential of the test article to cause acute dermal irritation or corrosion was assessed by a topical application of 2x 0.5 g of the test substance to two test sites on the intact skin of 6 white New Zealand rabbits for 4 hours under semi-occlusive dressing. The only irritation seen was slight (barely perceptible) erythema in three of the six animals, which subsided within one to three days. The average score (24 to 72 hours) for irritation was calculated to be 0.1 for erythema and 0.0 for edema.

 

Eye irritation:

In the key study (BIO/DYNAMICS, 1998; Validity 2) performed according to EPA-guideline OPP 81-4 (Acute Eye Irritation) and GLP, the potential of the test article to cause damage to the eye was assessed in 6 white New Zealand rabbits, subjected to a single occular application of 1cm³ volume of the test substance. All six animals exhibited severe conjunctival irritation (redness, chemosis, discharge, necrosis), corneal opacity, ulceration and iridial damage. All six animals also exhibited pannus (neovascularization of the corneal surface) one or more times between days 7 and 28. On day 7 one animal had an enlarged blood vessel on the anterior surface of the iris. Two animals had a fluid filled blister on the corneal surface on day 21 and/or 28. The effects were not reversible within the 28-day observation period.

Respiratory Irritation:

There are several epidemiological studies linking upper respiratory symptoms to vanadium pentoxide exposure (Kiviluoto, 1980; Kiviluoto et al., 1979a; Lewis, 1959, Zenz and Berg, 1967 Zenz et al. 1962). Effects were observed even after single exposure (e.g. Zenz & Berg, 1967). Long-term chronic exposure data of workers in the vanadium industry are reported in several publications by Kiviluoto et al. In a factory manufacturing vanadium pentaoxide, 63 workers exposed toV2O5 at concentrations of 0.1 to 3.9 mg V/m3 measured as total dust for 11 years (average 0.2-0.5 mg V/m3) did not have an increased prevalence of upper respiratory symptoms in the case study by Kiviluoto et al (1979a,b, 1980, 1981a,b). However, other epidemiological data support that respiratory symptoms are observed at exposure concentrations of V2O5 that are above 0.1 mg/ V/m3.

According to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, Annex VI, V2O5 is classified with STOT SE 3.


Justification for classification or non-classification

Based on the available data on the registered substance and as well as the pentavalent vanadium compound Divanadium pentoxide (CAS 1314-62-1) and according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 Divanadyl pyrophosphate (CAS 65232-89-5) has to be classified as Eye Damage 1 (H318) and STOT SE 3 (H335). No classification for skin irritation is warrented.