Tris(pentane-2,4-dionato-O,O')vanadium

Endpoint summary

Description of key information

The parent compound Vanadium-tris-acetylacetonate is rapidly hydrolysed to 2,4 -pentanedione (CAS no. 123 -54- 6) and Vanadyl acetylacetonate (CAS no. 3153 -26 -2) in the presence of water or moisture (> 80% hydrolysis after 1h at pH 1.2, 4, 7 and 9). Hence, the half life is < 1 h under neutral and acidic conditions. Accordingly, reliable data of the hydrolysis products 2,4-Pentadione (Cas no. 123-54-6) and Vanadyl acetylacetonate (3153-26-2) or comparable inorganic Vanadium compounds are used to address the endpoint, which is entirely appropriate to draw conclusions on the potential of Vanadium-tris-acetylacetonate to cause sensitisation to the skin of mammals.

Acetylacetonate, LLNA (OECD TG 429, GLP): not sensitising

V₂O₅, human patch test: not sensitising

V₂O₅, monkey, inhalation, 26 weeks: not sensitising

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2008-11-03 - 2008-11-21

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Version / remarks:

OECD Guideline for the testing of chemicals 429. Skin Sensitisation: Local Lymph Node Assay (Adopted: 22 July 2010)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Bayerisches Landesamt für Arbeitsschutz, Arbeitsmedizin und Sicherheitstechnik, 21 July 2004

Type of study:

mouse local lymph node assay (LLNA)

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature and protected from light

Species:

mouse

Strain:

CBA:J

Remarks:

CBA/J Rj

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Janvier, F - 53940 Le Genest-Saint-Isle
- Females (if applicable) nulliparous and non-pregnant: not specified
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 21 - 25 g
- Housing: The animals were kept in IVC cages, type II L, Polysulphone cages on Altromin saw fiber bedding.
- Diet (e.g. ad libitum): Feeding ad libitum, Altromin 1324 maintenance diet for rats and mice
- Water (e.g. ad libitum): Free access to tap water, sulphur acidified to a pH value of approx. 2.8 (drinking water, municipal residue control, microbiol. controlled at regular intervals)
- Acclimation period: Adequate acclimatisation period (at least 5 days)
- Indication of any skin lesions: Prior to the application and once a day thereafter all animals were observed in order to detect special clinical signs or reactions to treatment. At the daily clinical observation the animals did not show any visible clinical symptoms and no lesions were stated.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 55 ± 10 %
- Air changes (per hr): The animals were barrier maintained (semi-barrier) in an air conditioned room (Air change: at least 10 x / hour).
- Photoperiod (hrs dark / hrs light): Artificial light, sequence being 12 hours light, 12 hours dark

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

10 % and 50 % test item concentration and 100 % AOO as negative control (preliminary test)
12.5 %, 25 % and 50 % test item concentration and 100 % AOO as negative control (main test)

No. of animals per dose:

2 females per test concentration and 1 animal for the negative control (preliminary test)
5 females per test concentration and for the negative control (main test)

Details on study design:

PRE-SCREEN TESTS:
- Compound solubility: not specified
- Irritation: Two animals were treated by topical application to the entire dorsal surface of each ear with the test item. One animal was treated in the same way for the negative control. Excessive local skin irritation is indicated by an erythema score ≥ 3 and/or an increase in ear thickness of ≥ 25 %.
- Systemic toxicity: All mice were observed daily for any clinical signs of toxicity or local irritation at the application site. Cageside observations included spontaneous activity, lethargy, recumbent position, convulsions, tremors, apnoe, asphyxia, vocalisation, diarrhoea, changes in the skin and fur, eyes and mucous membranes (salivation, discharge).
- Ear thickness measurements: Ear thickness was measured on Day 1, 2, 3 and 4.
- Erythema scores: Erythema scores were scored according to the guideline.

MAIN STUDY

ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: The animals were randomly selected.
- Criteria used to consider a positive response: The LLNA measures the proliferation of lymphocytes isolated from lymph nodes (auricular lymph nodes) draining the site of exposure (dorsal aspect of the ears) in mice. Lymphocyte proliferation is measured by determining the incorporation of 3H-methyl thymidine. A substance is regarded as `sensitiser´ in the LLNA if at least one concentration of the test item results in a 3 fold or greater increase in H-methyl thymidine - incorporation into lymph node cells of the lymph nodes of the test group animals, relative to that recorded for the lymph nodes of control group animals (Stimulation Index equal to or greater than 3.0).

TREATMENT PREPARATION AND ADMINISTRATION:
Each animal was identified and the body weight was recorded prior to the application and at the end of the test period. Identification was ensured by cage number and individual marking (tail). Prior to the application and once a day thereafter all animals were observed in order to detect special clinical signs or reactions to treatment.
- Topical Application: Each mouse was treated by topical application of 25 µL of the selected solution to the entire dorsal surface of each ear. Topical applications were performed once daily over three consecutive days.
- Administration of 3H-methyl thymidine: Five days after the first topical application treatment all mice were dosed with 20 µCi 3H-methyl thymidine by intravenous injection (tail vein) of 250 µL of 3H-methyl thymidine, diluted to a working concentration of 80 µCi/mL.
- Preparation of cell suspension: Approximately 5 hours after 3H-methyl thymidine-injection all mice were sacrificed. The draining "auricular lymph nodes" were excised and individually pooled for each animal (2 lymph nodes per animal) and collected in phosphate buffered saline (PBS). A single cell suspension of pooled lymph node cells was prepared by gentle mechanical disaggregation through polyamide gauze (200 mesh size). After washing the gauze with PBS the cell suspension was pelleted in a centrifuge. The supernatant was discarded and the pellets were resuspended with PBS. This washing procedure was repeated.
After the final wash each pellet was resuspended in approx. 1 mL 5 % TCA at approx. 4 °C overnight for precipitation of macromolecules. Each precipitate was once washed again, resuspended in 1 mL 5 % TCA and 5 mL scintillation fluid was added. Then this solution was transferred into scintillation vials and stored at room temperature overnight.
- Determination of incorporated 3H-methyl thymidine: The 3H-methyl thymidine - incorporation was measured in a B-counter and expressed as the number of disintegrations per minute (DPM). Similarly, background 3H-methyl thymidine levels were also measured (5 % TCA). Determination of radioactivity was performed individually for each animal.

Positive control substance(s):

other: P-Phenylenediamine (CAS 106-50-3, Sigma, purity > 98 %; Lot 057K0052) 1 %

Positive control results:

SI = 7.0 +/- 0.9 (see "Any other information on results inc. tables")

Key result

Parameter:

SI

Value:

0.8

Test group / Remarks:

Test item, 50 %

Parameter:

SI

Value:

0.6

Test group / Remarks:

Test item, 25 %

Parameter:

SI

Value:

0.9

Test group / Remarks:

Test item, 12.5 %

Parameter:

SI

Value:

7

Test group / Remarks:

positive control

Parameter:

SI

Value:

1

Test group / Remarks:

negative control

Key result

Parameter:

EC3

Test group / Remarks:

Test item

Remarks on result:

not determinable

Cellular proliferation data / Observations:

CELLULAR PROLIFERATION DATA
Lymph Node Proliferation
Approximately 5 hours after 3H-methyl thymidine-injection all mice were sacrificed. The draining "auricular lymph nodes" were excised and weighed individually. In comparison with the control group, an increase of the pooled lymph node weight was not recorded at used concentrations. The pooled lymph node weights of treated groups were 2.1 mg for 12.5 % concentration, 2.1 mg for 25 % concentration and 2.3 for 50 % concentration of tested item. The lymph node weight of the negative control group was 3.3 mg. The mean DPM values for the three treated groups and the negative control were 1042.0 (12.5 %), 684.0 (25 %), 895.4 (50 %) and 1135.6 (negative control), respectively. The EC3 value (derived by linear interpolation) could not be stated, as all measure points were below the stimulation index of three.

DETAILS ON STIMULATION INDEX CALCULATION
A single cell suspension of the lymph node cells for each animal was prepared. The 3H-methyl thymidine incorporation was measured in a B-counter and expressed as the number of disintegrations per minute (DPM). Determination of radioactivity was performed individually for each animal.
The proliferative response of lymph node cells was calculated as the ratio of 3H-methyl thymidine incorporation into lymph node cells of test group animals relative to that recorded for control group animals. A stimulation index, ratio of test item / negative control, was calculated for each concentration.

EC3 CALCULATION
Calculated SI values in treated groups remained under the value of 3, which is the threshold to consider the substance a sensitizer. Therefore, it was not possible to calculate an EC3 value.

CLINICAL OBSERVATIONS:
At the daily clinical observation the animals did not show any visible clinical symptoms. All animals survived throughout the test period without showing any clinical signs.

BODY WEIGHTS
Weight development of all animals was within the expected range (with the exception of two animals which lost 3 g), which includes a weight loss of up to 2 g throughout the study.

 Results of the Reliability check

POS	CPMA	Test Item	Conc. [%]	Animal number	DPM	DPM Mean background	DPM / Node	Stimulation Index
18	609.0	Negative		16	1705.0	1687.2	843.6
19	426.0	Control		17	1191.0	1173.2	586.6
20	569.0			18	1586.0	1568.2	784.1
21	760.0			19	2158.0	2140.2	1070.1
22	436.0			20	1223.0	1205.2	602.6
MV	560.0			MV	1572.6	1554.8	777.4	1.0
SD	123.1			SD	354.5	354.5	177.2
114	609.0	Phenylene-		1	10988.0	10970.2	5485.1	7.1
115	426.0	Diamine		2	9686.0	9668.2	4834.1	6.2
116	569.0			3	124010	12383.2	6191.6	8.0
117	760.0			4	8990.0	8972.2	4486.1	5.8
118	436.0			5	12279.0	12261.2	6130.6	7.9
MV	560.0			MV	10868.8	10851.0	5425.5	7.0
SD	123.1			SD	1362.3	1362.3	681.2	0.9
121	5.0	Background			14.0
122	8.0	Szinti and			21,0
123	7.0	TCA			19,0
124	6.0				17.0
125	7.0				18.0
MV	6.6			MV	17.8	0.0	0.0	0.0
SD	1.0			SD	2.3

Szinti = scintillation fluid; TCA = trichloroacetic acid; MV = Mean Value; SD = Standard Deviation

DPM = disintegrations per minute, CPM = counts per minute

Interpretation of results:

GHS criteria not met

Remarks:

Substance is not a skin sensitiser

Conclusions:

The study was conducted under GLP according to OECD guideline 429. The method is to be considered scientifically reasonable with no deficiencies in documentation or any deviations, the validity criteria are fulfilled, positive and negative controls gave the appropriate response. Hence, the results can be considered as reliable to assess the sensitising potential of Acetylacetone in mice.
All animals survived throughout the test period without showing any clinical signs of toxicity or local irritation. Calculated SI values in treated groups remained under the value of 3, which is the threshold to consider the substance a sensitiser. Accordingly, the EC3 value (derived by linear interpolation) could not be stated. Results of radioactivity determination are supported by the second endpoint, means of the lymph node weights per group, which did not show dose-related increased values compared to negative control values as well.
Acetylacetone was so identified as a non-sensitizsng agent in the Local Lymph Node Assay.

Executive summary:

The sensitisation potential of Acetylacetone was evaluated using the Local Lymph Node Assay (LLNA) in a OECD 429 guideline study under GLP. The LLNA has been developed to determine the allergic contact sensitisation potential of chemicals.

Based on the recommendations of the OECD Guideline 429, the test item was dissolved in acetone:olive oil 4:1 (v/v) (AOO).

The preliminary test was performed using a dose of 10 and 50 % (w/v) beside the negative control with 100 % AOO. Based on the results of the preliminary test the test item Acetylacetone was assayed for sensitising properties at concentrations of 12.5 %, 25 % and 50 % (v/v).

Five female mice ( CBA/J Rj) per group were treated by topical application to the entire dorsal surface of each ear to the test item at concentrations of 25 %, 50 % and 100 % and to the vehicle only (negative control). Lymphocyte proliferation is measured by determining the incorporation of 3H-methyl thymidine in the draining lymph nodes. The radioactive incorporation was expressed as disintegrations per minute (DPM)/pooled treatment group and compared with DPM value from the vehicle control group and expressed as the Stimulation Index (SI).

After application of the test item at three concentrations (12.5 %, 25 % and 50 % w/v) all animals survived without showing any visible clinical symptoms of either local irritation or systemic toxicity. Weight development of all animals was within the expected range (with the exception of two animals which lost 3 g), which includes a weight loss of up to 2 g throughout the study.

In this study Stimulation Indices (SI) of 0.9, 0.6 and 0.8 were determined with the test item at concentration of 12.5, 25 and 50 % in AOO, respectively. The EC3 value could not be calculated, as all measured points were below the Stimulation Index of three. Results of radioactivity determination are supported by the second endpoint, means of the lymph node weights per group, which did not show dose-related increased values compared to negative control values as well.

Considering the reported data of this sensitisation test it can be stated that the test item Acetylacetone is not a skin sensitiser.

Reference 2

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

October 1991 - January 1992

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable well documented publication which meets basic scientific principles.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

no guideline followed

Principles of method if other than guideline:

126 enamellers and 64 decorators from 5 factories underwent dermatological and allergological examination using occupational test series in order to evaluate the prevalence of dermatitis and contact sensitisation, and to identify the most important sensitising substances

GLP compliance:

no

Type of study:

patch test

Justification for non-LLNA method:

patch test in human serves as weight-of-evidence

Specific details on test material used for the study:

The test material was obtained directly from chemical industries supplying ceramic producers.

Species:

other: human

Sex:

male/female

Route:

epicutaneous, semiocclusive

Vehicle:

petrolatum

Concentration / amount:

10 %

Route:

epicutaneous, semiocclusive

Vehicle:

petrolatum

Concentration / amount:

10 %

Details on study design:

For establishing dilutions of vanadium pentoxide 100 of the subjects undergoing standard patch testing were patch tested with vanadium pentoxide at the concentrations 1, 2 and 10 %.

Positive control substance(s):

no

Remarks:

allergens from different groups of chemical substances

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

10 %

No. with + reactions:

1

Total no. in group:

190

Clinical observations:

the sensitised persons represent 0.005 %

Group:

positive control

Remarks on result:

not measured/tested

Group:

negative control

Remarks on result:

not measured/tested

No skin reactions to patch tests performed with vanadium pentoxide at different concentrations (1, 2 and 10%) were observed in 100 subjects undergoing standard patch testing. Dermatitis was present in 22 workers (11.57 %). whereas 44 subjects (23.15 %) claimed to have had skin lesions in the past. In all subjects, the hands were or had been affected, and in 5 patients the forearms were also involved. 48 workers (corresponding to 25.26 % of the study population) were either mono- (42 subjects) or poly-sensitised (6 subjects), with a total of 55 positive patch tests. Table 2 shows the list of allergens which brought about positive responses. 28 subjects (14.73 % of the total) were positive to nickel sulphate; of these, 17 were women. Furthermore, there were 17 positive reactions to substances specific to the ceramics industry: 7 to red iron oxide; 2 to antimony trioxide, manganese dioxide and maleic anhydride; 1 to red copper oxide, cadmium chloride, vanadium pentoxide and sodium tripolyphosphate.

Table 2. No. sensitisations to substances used in the ceramics Industry in enamellers and decorators

Hapten	Total 190 (100 %)	Enamellers 126 (100 %)	Decorators 64 (100 %)
nickel sulphate	28 (14.7 %)	8 (6.3 %)	20 (31.2 %)
red iron oxide	7	6	1
cobalt chloride	5	2	3
antimonv irioxide	2	1	1
mercapto mix	2	1	1
manganese dioxide	2	1	1
maleic anhydride	2	1	1
potassium diehromaie	1	0	1
red copper oxide	1	1	0
cadmium chloride	1	1	0
carba mix	1	1	0
PPD mix	1	1	0
vanadium pentoxide	1	1	0
sodium tripolyphosphate	1	1	0

Interpretation of results:

GHS criteria not met

Conclusions:

In this study, 1 out of 190 workers (0.005 % of the test subjects) was positive in patch test to vanadium pentoxide (10 % in petrolatum).

Executive summary:

126 enamellers and 64 decorators from 5 factories underwent dermatological and allergological examination using occupational test series in order to evaluate the prevalence of dermatitis and contact sensitisation, and to identify the most important sensitising substances. 44 workers (corresponding to 25.26 % of the study population) were sensitised, with a total of 55 positive patch tests. Dermatitis was present in 22 workers, whereas 44 subjects claimed to have had skin lesions in the past. 17 positivities to specific substances were observed: 7 to red iron oxide; 2 to antimony trioxide, manganese dioxide and maleic anhydride; and 1 to red copper oxide, cadmium chloride, vanadium pentoxide and sodium tripolyphosphate.

No skin reactions to patch tests performed with vanadium pentoxide at different concentrations (1, 2 and 10 %) were observed in 100 subjects undergoing standard patch testing.

1 out of 190 workers (0.005 % of the test subjects) was positive in patch test to vanadium pentoxide (10 % in petrolatum).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

A study on acetylacetonate was conducted under GLP according to OECD Guideline 429. The method is to be considered scientifically reasonable with no deficiencies in documentation or any deviations, the validity criteria are fulfilled, positive and negative controls gave the appropriate response. Hence, the results can be considered as reliable to assess the sensitising potential of acetylacetone in mice. All animals survived throughout the test period without showing any clinical signs of toxicity or local irritation. Calculated SI values in treated groups remained under the value of 3, which is the threshold to consider the substance a sensitiser. Accordingly, the EC3 value (derived by linear interpolation) could not be stated. Results of radioactivity determination are supported by the second endpoint, means of the lymph node weights per group, which did not show dose-related increased values compared to negative control values as well. Thus, acetylacetone was identified as a non-sensitising agent in the Local Lymph Node Assay (BSL 2009).

The skin sensitising potential V₂O₅ was studied in human patch test. 126 enamellers and 64 decorators from 5 factories underwent dermatological and allergological examination using occupational test series in order to evaluate the prevalence of dermatitis and contact sensitisation, and to identify the most important sensitising substances. No skin reactions to patch tests performed with vanadium pentoxide at different concentrations (1, 2 and 10%) were observed in 100 subjects undergoing standard patch testing. 1 out of 190 workers (0.005 % of the test subjects) was positive in patch test to vanadium pentoxide (10 % in petrolatum) (Motolese 1993).

Respiratory sensitisation

Link to relevant study records

Reference

Endpoint:

respiratory sensitisation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

please refer to Read-across statement attached in section 13

Reason / purpose for cross-reference:

read-across source

Results:

Pulmonary response in post-exposure provocation tests:
Post-eposure reactivity was not significantly different between the three exposure groups at either challenge concentration. However, a trend (not statistically significant) toward decreased post-exposure challenge reactivity in the two pulmonary function variables RL (pulmonary flow resistance) and FEF50/FVC (forced expiratory flow/forced vital capacity) was noted in the vanadium pentoxide-exposed groups as compared to the control group at the 3.0 mg vanadium pentoxide/m3 level.
The respiratory system was highly reactive to provocation challenges with methacholine. Dramatic increases in RL (P <0.001) and decreases in FEF50/FVC (P < 0.001) were measured at the 6.25 mg/mL methacholine concentration. Methacholine reactivity was not significantly increased by subchronic vanadium pentoxide exposure; however, a trend toward a post-exposure decrease in RL was observed in the vanadium pentoxide-exposed groups that was similar to that observed for post-exposure vanadium pentoxide reactivity.

Regarding the cytological and immunological investigations, a post-exposure trend (statistically significant for eosinophils) toward decreased responses was observed in the vanadium pentoxide-exposed groups as compared to the control group.
The number of circulating neutrophils and eosinophils in venous blood was not affected by subchronic vanadium pentoxide exposure. The number of circulating neutrophils during pre-exposure testing was 6.6 ± 0.5, and 6.6 ± 0.8, 6.1 ± 1.2 and 8.6 ± 2.6 x 10E3 cells/mm3 for the Control, Peak and Constant groups, respectively, during post-exposure testing. The number of eosinophils was 0.22 ± 0.05, and 0.24 ± 0.09, 0.14 ± 0.06 and 0.26 ± 0.09 x 10E3 cells/mm3, respectively. Similarly, serum immunoglobulins were unchanged throughout the study, averaging 1070 ± 61, and 1107 ± 81, 1095 ± 122 and 1159 ± 111 mg/dL for IgG; and 37.4 ± 1.5. and 42.7 ± 3.5. 43.0 ± 3.7 and 44.5 ± 2.4 ng/mL for IgE.

Positive control results:

not applicable

Animal Observations:

Respiratory distress developed in three monkeys from the Peak group during the subchronic vanadium pentoxide exposures. The pattern of effect was characterized by audible wheezing and

coughing, and occurred only on peak exposure days during the first few weeks of exposure. Responses developed within 3-4 h of exposure, and occasionally required early removal of the affected monkeys from the exposure chamber. Through careful animal monitoring, these three monkeys continued to receive daily exposures for the entire study.

Pre-exposure provocation challenges:

The pre-exposure provocation challenges with vanadium pentoxide (V₂O₅) produced statistically significant impairments in pulmonary function at an aerosol concentration of 3.0 mg V₂O₅/m³, but not at 0.5 mg V₂O₅/m³. Significant changes in the hypothesis-testing variables (RL and FEFSU/FVC) were observed. The increase in RL and the decrease in FEF50/FVC were accompanied by a significant increase in RV and a significant decrease in FVC, thereby demonstrating an obstructive pattern of impaired pulmonary function.

Pre-exposure challenge also produced a cellular response characterized by a significant increase in the total number of respiratory cells recovered from the lung by bronchoalveolar lavage (BAL). The increase in the total number of cells occurred through a highly significant increase (P < 0.001) in the number of PMNs. The number of eosinophils recovered from the lung was also increased, while the numbers of lymphocytes, macrophages and mast cells were not. Significant challenge responses were not observed for total protein, albumin, LTC4 or the immunoglobulins, despite the significant cellular response to vanadium pentoxide challenge.

Pulmonary responses during subchronic exposure:

The pattern of pulmonary function observed when the monkeys were rechallenged following subchronic exposure resembled the obstructive pattern measured in response to the pre-exposure

V2O5 challenges. In addition, the pattern of the cellular and immunological response observed after subchronic exposure was similar to the responses to the pre-exposure challenges.

Beside pulmonary function, skin sensitivity tests were also performed. Skin sensitivity to both skin test solutions, i.e. sodium vanadate and vanadium pentoxide-MSA conjugate, averaging < 1 was observed for both the immediate and delayed responses, and remained unchanged after subchronic exposure, supporting the indicated absence of allergic sensitisation.

Interpretation of results:

GHS criteria not met

Conclusions:

No increase in pulmonary reactivity as well as no skin response was found in monkeys after subchronic inhalation exposure to vanadium pentoxide for 26 weeks. This indicates that under these conditions, vanadium pentoxide did not induce allergic sensitisation in monkeys upon inhalation exposure.

Executive summary:

No regulatory accepted test guideline exists for the determination of a respiratory sensitisation potential of chemicals. The potential of the test item vanadium pentoxide to induce sensitisation upon subchronic inhalation exposure was studied in monkeys. Groups of 8 monkeys were exposed to vanadium pentoxide for 26 weeks. Pulmonary responses as well as cytological and immunological parameters measured after the subchronic exposure period were compared with measurements conducted prior to exposure. Here, no increased but a rather decreased pulmonary reactivity was found after subchronic inhalation exposure. In addition, cytological and immunological parameters as well as the negative skin test results indicate the absence of allergic sensitisation. Overall, the test item vanadium pentoxide was not found as a respiratory sensitiser after subchronic inhalation exposure in monkeys.

This indicates that no respiratory sensitising potential can be attributed to the vanadium compounds formed as hydrolysis product from the target substance vanadium-tris-acetylacetonate.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

No regulatory accepted test guideline exists for the determination of a respiratory sensitisation potential of chemicals. The potential of the test item vanadium pentoxide to induce sensitisation upon subchronic inhalation exposure was studied in monkeys. Groups of 8 monkeys were exposed to vanadium pentoxide for 26 weeks. Pulmonary responses as well as cytological and immunological parameters measured after the subchronic exposure period were compared with measurements conducted prior to exposure. Here, no increased but a rather decreased pulmonary reactivity was found after subchronic inhalation exposure. In addition, cytological and immunological parameters as well as the negative skin test results indicate the absence of allergic sensitisation. Overall, the test item vanadium pentoxide was not found as a respiratory sensitiser after subchronic inhalation exposure in monkeys.

This indicates that no respiratory sensitising potential can be attributed to the vanadium compounds formed as hydrolysis product from the target substance vanadium-tris-acetylacetonate.

Justification for classification or non-classification

Based on the available information on the source substances acetylacetonate and vanadium pentoxide, no classification of the target substance vanadium-tris-acetylacetonate is triggered in accordance with Regulation (EC) No 1272/2008.