Vanadate(1-), oxo[phosphato(3-)-.kappa.O]-, hydrogen, hydrate (2:2:1)

Endpoint summary

Description of key information

skin irritation: negative

seious eye damage: positive

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:

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

Guideline:

EPA OPP 81-5 (Acute Dermal Irritation)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system 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): 0.5 grams per site; two intact sites per animal
- % coverage: at least 10 % of the body area

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

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:

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

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

Observation period (in vivo):

max. 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): Approximately 24 h after application, the treated eyes were rinsed to remove any residual test application.

SCORING SYSTEM: draize score, with the following deviations:

Cornea:
Opaclity - degree of density
No opacIty = 0
SIight dulling of normal luster = +
Scattered or difuse areas of opacity (other than slight dulling of normal luster). details of iris clearly visible . = 1*
Easily discerniole transluscent areas; details of iris slightly obscured = 2*
Nacrous area. no detalles of iris visible, size of pupil barely discernible = 3*
Opaque cornea, iris not discernisle through opacity = 4*

Iris
Normal = 0
Slight deepening of the rugae or slight hyperemia of the circumcorneal blood vessels = +
Markedly deepened folds (above normal). congestion, swelling, moderate circumcorneal hyperemia or injection (any or all of these or combination of thereof), iris still reacting to light (sluggish reaction is positive} = 1*
No reaction to light, hemorrhage, gross destruction (any or all of these} = 2*

"*" = Score considered positive;
"+" = Not included in SPA grading system, values assigned if finding present.

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 in 3 of 6 animals

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 in 3 of 6 animals

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 in 2 of 6 animals

Other effects:

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 (vascularized connective tissue like excrescence) 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).

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	4/+/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	2/2/2/2/2/1		2/1/1/1/0/0
21 d	+/+/1/1/0/0	1/0/0/0/0/0	1/1/1/1/1/1		1/0/0/1/0/0
28 d	2/+/2/2/0/0	0/0/0/0/0/0	1/1/0/1/0/0		1/0/0/1/0/0

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

There are no substance specific information on Vanadate(1-), oxo[phosphato(3-)-κO]-, hydrogen, hydrate (2:2:1) for skin, eye and respiratory irritaion available. However, data from other vanadium compounds were taken into account to access the respective endpoint.

Skin Irritation:

A study was conducted to evaluate the dermal irritation produced by E-326 Catalyst (Divanadyl pyrophosphate, CAS 65232 -89-5) in rabbits when administered for a 4-hour interval under a semi-occlusive covering (BASF, 1989). E-326 Catalyst produced mild and transient dermal irritation. The only irritation seen was very slight (barely perceptible) erythema in three of the six animals which subsided within one to three days. The Average Dermal Irritation Score of E-326 Catalyst is 0.1.

 

Eye Irritation:

The study was conducted to evaluate the ocular irritation produced by E-326 Catalyst (Divanadyl pyrophosphate, CAS 65232 -89-5) in rabbits. E-326 Catalyst was corrosive to the eye. All six animals exhibited severe conjunctival irritation (redness, chemosis, discharge, necrosis), corneal opacity and 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 exhibited residual test material in the eye at 1 and 24 hours. All six animals continued to exhibit severe irritation at termination of the study (Day 28).

 

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

Currently there is no substance specific data on Vanadate(1-), oxo[phosphato(3-)-κO]-, hydrogen, hydrate (2:2:1) for skin irritation / corrosion and eye irritation available. However data from the source compound Divanadyl pyrophosphate (CAS 65232-89-5) as well as the pentavalent vanadium compound Divanadium pentoxide (CAS 1314-62-1) can be taken into account for hazard assessment.

Based on the available data and according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008

Vanadate(1-), oxo[phosphato(3-)-κO]-, hydrogen, hydrate (2:2:1) has to be classified as Eye Damage 1 (H318) and STOT SE 3 (H335). No classification for skin irritation is warrented.