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 acute toxicity of Vanadium-tris-acetylacetonate to mammals.

oral

V₂O₅ rat, single dose LD50 = 467 mg/kg bw (female), 470 mg/kg bw (male) - VAA LD50 = 1788 mg/kg bw (female), 1799.5 mg/kg bw (male)

V₂O₃ rat, single dose LD50 = 5639 mg/kg bw (female), 8713 mg/kg bw (male) - VAA LD50 = 26216 mg/kg bw (female), 40507 mg/kg bw (male)

NH₄VO₃ rat, single dose LD50 = 141 mg/kg bw (female), 218 mg/kg bw (male) - VAA LD50 = 424.2 mg/kg bw (female), 655.8 mg/kg bw (male)

Acetylacetone rat, single dose LD50 = 578 mg/kg bw (female), 760 mg/kg bw (male)

inhalation

V₂O₅ rat, dust, 4 h, LC50 = 4.3 mg/L (female), 11.09 mg/L (male) - VAA LC50 = 16.5 mg/L (female), 42.5 mg/L (male)

V₂O₃ rat, dust, 4 h, LC50 > 6.65 mg/L (female) - VAA LC50 > 30.9 mg/L (female)

NH₄VO₃ rat, dust, 4 h, LC50 = 2.43 mg/L (female), 2.61 mg/L (male) - VAA LC50 = 7.3 mg/L (female), 7.9 mg/L (male)

Acetylacetone rat, vapour, 4 h LC50 = 5.2 mg/L (female), 5.1 mg/L (male/female)

dermal

V₂O₅ rat, 24 h, LD50 > 2500 mg/kg bw - VAA LD50 > 9571.6 mg/kg bw

V₂O₃ rat, 24 h, LD50 > 2500 mg/kg bw - VAA LD50 > 11622.7 mg/kg bw

NH₄VO₃ rat, 24 h, LD50 > 2500 mg/kg bw - VAA LD50 > 7520 mg/kg bw

Acetylacetone rabbit, 24 h LD50 = 793.8 mg/kg bw (female), 1381.8 mg/kg bw (male)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

weight of evidence

Justification for type of information:

please refer to Read-across statement attached in section 13

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

1 799.5 mg/kg bw

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

1 788 mg/kg bw

Based on:

test mat.

Sex:

male

Dose descriptor:

other: No-effect level

Effect level:

823.2 mg/kg bw

Based on:

test mat.

Sex:

female

Dose descriptor:

other: No-effect level

Effect level:

823.2 mg/kg bw

Based on:

test mat.

Calculation of LD50 of vanadium acetylacetonate:

EC(V) in source substance

Source substance V2O5

MW (V2O5) = 181.88 g/mol

MW (V) = 50.94 g/mol

V in V2O5 = (2*50.94) / 181.88 = 0.56

EC (V) = EC(V2O5) x 0.56 = 470 mg/kg bw x 0.56 = 263.20 mg/kg bw

EC of target substance vanadium acetylacetonate (VAA)

MW V in VAA = 50.94 g/mol

MW VAA = 348.27 g/mol

EC (VAA) in target = EC (V) in source / 50.94 x 348.27

EC (V) in source = 263.2 mg/kg bw

EC (VAA) in target = 263.2 / 50.94 x 348.27 = 1799.46 mg/kg bw

The further values are calculated accordingly.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 for vanadium pentoxide is reported to be 470 mg/kg bw for male rats and 467 mg/kg bw for female rats. These values corresponds to an LD50 of 1799.5 mg/kg bw for male rats and to a LD50 of 1788.0 mg/kg bw for female rats for vanadium acetylacetonate.

Executive summary:

The acute oral toxicity of vanadium pentoxide (CAS 1314 -62 -1) was studies similar to OECD Guideline 401. Following administration, observations were made and recorded systematically with individual records being maintained for each animal. Observations were performed immediately, 5, 15, 30 and 60 min, as well as 3 h, 6 h and 24 h after administration. Then twice daily for a period of 14 days. The time of death was recorded as precisely as possible. Individual body weights were recorded before administration of the substance, thereafter in weekly intervals up to the end of the study, and at death. At the end of the experiments all surviving animals were sacrificed, dissected and inspected macroscopically. All gross pathological changes were recorded. Autopsy and macroscopic inspection of rats which died prematurely were carried out as soon as possible after exitus.

The LD50 for vanadium pentoxide is reported to be 470 mg/kg bw for male rats and 467 mg/kg bw for female rats. These values correspond to an LD50 of 1799.5 mg/kg bw for male rats and to a LD50 of 1788.0 mg/kg bw for female rats for vanadium acetylacetonate.

For details regarding the calculation path please see section “Any other information on results incl. tables”.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

weight of evidence

Justification for type of information:

please refer to Read-across statement attached in section 13

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

40 507.3 mg/kg bw

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

26 216.1 mg/kg bw

Based on:

test mat.

Sex:

male

Dose descriptor:

other: No-effect level

Effect level:

21 571.7 mg/kg bw

Based on:

test mat.

Sex:

female

Dose descriptor:

other: No-effect level

Effect level:

21 571.7 mg/kg bw

Based on:

test mat.

Calculation of LD50 of vanadium acetylacetonate:

EC(V) in source substance

Source substance V2O3

MW (V2O3) = 149.88 g/mol

MW (V) = 50.94 g/mol

V in V2O3 = (2*50.94) / 149.88 = 0.68

EC (V) = EC(V2O3) x 0.68 = 8713 mg/kg bw x 0.68 = 5924.84 mg/kg bw

EC of target substance vanadium acetylacetonate (VAA)

MW V in VAA = 50.94 g/mol

MW VAA = 348.27 g/mol

EC (VAA) in target = EC (V) in source / 50.94 x 348.27

EC (V) in source = 5924.84 mg/kg bw

EC (VAA) in target = 5924.84 / 50.94 x 348.27 = 40507.3 mg/kg bw

The further values are calculated accordingly.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 for vanadium trioxide is reported to be 8713 and 5639 mg/kg bw for male rats and female rats, respectively. These values correspond to a LD50 of 40507.3 mg/kg bw for male rats and to a LD50 of 26216.1 mg/kg bw for female rats for vanadium acetylacetonate.

Executive summary:

The acute oral toxicity of vanadium (III) oxide (CAS 1314 -34 -7) was studies similar to OECD Guideline 401. Following administration, observations were made and recorded systematically with individual records being maintained for each animal. Observations were performed immediately, 5, 15, 30 and 60 min, as well as 3 h, 6 h and 24 h after administration. Then twice daily for a period of 14 days. The time of death was recorded as precisely as possible. Individual body weights were recorded before administration of the substance, thereafter in weekly intervals up to the end of the study, and at death. At the end of the experiments all surviving animals were sacrificed, dissected and inspected macroscopically. All gross pathological changes were recorded. Autopsy and macroscopic inspection of rats which died prematurely were carried out as soon as possible after exitus.

The LD50-values for the V₂O₃test-substance (analytical grade, powder) following oral administration were 8713 mg/kg for male and 5639 mg/kg for female rats. These values correspond to a LD50 of 40507.3 mg/kg bw for male rats and to a LD50 of 26216.1 mg/kg bw for female rats for vanadium acetylacetonate.

For details regarding the calculation path please see section “Any other information on results incl. tables”.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

weight of evidence

Justification for type of information:

please refer to Read-across statement attached in section 13

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

655.8 mg/kg bw

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

424.2 mg/kg bw

Based on:

test mat.

Sex:

male

Dose descriptor:

other: No-effect level

Effect level:

300.8 mg/kg bw

Based on:

test mat.

Sex:

female

Dose descriptor:

other: No-effect level

Effect level:

139.6 mg/kg bw

Based on:

test mat.

Calculation of LD50 of vanadium acetylacetonate:

EC(V) in source substance

Source substance NH4VO3

MW (NH4VO3) = 116.98 g/mol

MW (V) = 50.94 g/mol

V in NH4VO3 = 50.94 / 116.98 = 0.44

EC (V) = EC(NH4VO3) x 0.44 = 218 mg/kg bw x 0.44 = 95.92 mg/kg bw

EC of target substance vanadium acetylacetonate (VAA)

MW V in VAA = 50.94 g/mol

MW VAA = 348.27 g/mol

EC (VAA) in target = EC (V) in source / 50.94 x 348.27

EC (V) in source = 95.92 mg/kg bw

EC (VAA) in target = 95.92 / 50.94 x 348.27 = 655.8 mg/kg bw

The further values are calculated accordingly.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 for ammonium vanadate is reported to be 218 and 141 mg/kg bw for male rats and female rats, respectively. Those values correspond to a LD50 of 655.8 mg/kg bw for male rats and to a LD50 of 424.2 mg/kg bw for female rats for vanadium acetylacetonate.

Executive summary:

The acute oral toxicity of ammonium metavanadate (CAS 7803 -55 -6) was studies similar to OECD Guideline 401. Following administration, observations were made and recorded systematically with individual records being maintained for each animal. Observations were performed immediately, 5, 15, 30 and 60 min, as well as 3 h, 6 h and 24 h after administration. Then twice daily for a period of 14 days. The time of death was recorded as precisely as possible. Individual body weights were recorded before administration of the substance, thereafter in weekly intervals up to the end of the study, and at death. At the end of the experiments all surviving animals were sacrificed, dissected and inspected macroscopically. All gross pathological changes were recorded. Autopsy and macroscopic inspection of rats which died prematurely were carried out as soon as possible after exitus.

The LD50 for ammonium vanadate is reported to be 218 and 141 mg/kg bw for male rats and female rats, respectively. These values correspond to a LD50 of 655.8 mg/kg bw for male rats and to a LD50 of 424.2 mg/kg bw for female rats for vanadium acetylacetonate.

For details regarding the calculation path please see section “Any other information on results incl. tables”.

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

weight of evidence

Justification for type of information:

please refer to Read-across statement attached in section 13

Reason / purpose for cross-reference:

read-across source

Sex:

male

Dose descriptor:

LD50

Effect level:

0.78 mL/kg bw

Based on:

test mat.

95% CL:

0.66 - 0.91

Sex:

female

Dose descriptor:

LD50

Effect level:

0.59 mL/kg bw

Based on:

test mat.

95% CL:

0.51 - 0.7

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

578 mg/kg bw

Based on:

test mat.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

760 mg/kg bw

Based on:

test mat.

Mortality:

Animals died within a few hours after the oral exposure.

Clinical signs:

other: Following oral administration, signs of toxicity observed at doses of 0.5 mL/kg included sluggish and unsteady gait by 30 min, prostation and lachrymation by 1.5 to 2 h, and tremor, twitching movements and convulsion at 2 to 3 h.

Gross pathology:

No gross pathology changes were seen in animals that died or sacrificed survivors.

Dosage (mL/kg)	Mortalities (No. dead/no. dosed)		Time to death
	male	female
1.0	5/5	5/5	2-3 h
0.71	1/5	5/5	5-24 h
0.5	0/5	0/5	-
0.25	0/5	0/5	-

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

LD50 = 760 mg/kg bw (male rats), 578 mg/kg bw(female rats)
This result is also valid for the target substance vanadium-tris-acetylacetonate, since the source substance acetylacetonate is a hydrolysis product of vanadium-tris-acetylacetonate.

Executive summary:

The acute toxicity of 2,4 -pentanedione (CAS 123 -54 -6) was studies similar to OECD Guideline 401 in rats. The test item was applied orally (by gavage) in 5 concentrations ranging from 0.25 to 1 mL/kg bw. Following oral administration, signs of toxicity observed at doses of 0.5 mL/kg included sluggish and unsteady gait by 30 min, prostation and lachrymation by 1.5 to 2 h, and tremor, twitching movements and convulsion at 2 to 3 h. Body weight was unaffected in survivors and no gross pathology changes were seen in animals that died or sacrificed survivors. The LD50 values were 760 mg/kg bw for male and 578 mg/kg bw for female rats. This result is also valid for the target substance vanadium-tris-acetylacetonate, since the source substance acetylacetonate is a hydrolysis product of vanadium-tris-acetylacetonate.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

424.2 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

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

Adequacy of study:

weight of evidence

Justification for type of information:

please refer to Read-across statement attached in section 13

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LC50

Remarks:

converted from ppm (please refer to 'Overall Remarks')

Effect level:

5 091.84 mg/m³ air

Based on:

test mat.

Exp. duration:

4 h

Sex:

female

Dose descriptor:

LC50

Remarks:

converted from ppm (please refer to 'Overall Remarks')

Effect level:

5 200 mg/m³ air

Based on:

test mat.

Exp. duration:

4 h

Sex:

female

Dose descriptor:

LC50

Effect level:

1 250 ppm

Based on:

test mat.

95% CL:

> 911 - < 1 716

Sex:

male/female

Dose descriptor:

LC50

Effect level:

1 224 ppm

Based on:

test mat.

95% CL:

> 1 063 - < 1 409

Sex:

female

Dose descriptor:

other: Lt50

Effect level:

7 912 ppm

Based on:

test mat.

Exp. duration:

55 min

Sex:

male

Dose descriptor:

other: Lt50

Effect level:

7 060 ppm

Based on:

test mat.

Exp. duration:

52 min

Mortality:

Study A, statically generated vapor atmoshere: All rats died during the longer exposures. No rat died as a result of the shorter exposures.
Study B, 4h exposure to dynamically generated vapor: Death occured either during exposure or in the first post-exposure day, with one exception at 3 days postexposure (1231 ppm, male rat).

Clinical signs:

other: Study A (statically generated vapor atmoshere): Short exposure (37 or 39 min): periocular wetness, mouth and abdominal breathing, hypoactivity, negative toe and tail pinch reflexes, and negative surface righting. Longer exposure (74 or 78 min): signs of t

Body weight:

Study A (statically generated vapor atmoshere):
Body weights were not affected by the short duration exposures.

Study B (4h exposure to dynamically generated vapor):
Body weights were unaffected in the survivors.

Gross pathology:

Study A (statically generated vapor atmoshere):
Necropsy of animals that died showed red coloration of the lungs, dark colored livers, and gas-filled stomachs.
Animals that survived showed no gross pathological features.

Study B (4h exposure to dynamically generated vapor):
Necropsy of animals that died showed dark red lungs, mottled livers, and gas-filled gastrointestinal tracts.
Animals that survived showed no gross pathological features.

Study A:

Table 1. Exposure conditions and mortalitites for rats exposed to atmospheres saturated with vapor from acetylacetonate.

Sex	Exposure time (min)	Measured concentration (ppm)	Chamber conditions*		Mortalities (No. dead/no. exposed)	Time to death
			Temperature (°C)	Relative humidity (%)
Male	74	7732	24±1	82±24	5/5	About 50 min
Male	37	6388	23±0	97±4	0/5	-
Female	78	8374	24±1	84±22	5/5	About 50 min
Female	39	7449	22±0	90±12	0/5	-

*as mean±SD

Study B:

Table 2. Mortality data for rats exposed for 4 h to differing concentrations of dynamically generated acetylacetonate vapor.

Concentration (ppm)	Mortalities (No. dead/no. exposed)		Time to death
	Male	Female
1508	3/5	5/5	Up to 1 day
1231	5/5	1/5	Up to 3 days
919	0/5	0/5	-
628	0/5	0/5	-

Interpretation of results:

other: according to CLP not classified (> 5 mg/L)

Conclusions:

LC50 (4h) = 5.2 mg/L air (female rats), 5.1 mg/L (combined value for male/female rats)
This result is also valid for the target substance vanadium-tris-acetylacetonate, since the source substance acetylacetonate is a hydrolysis product of vanadium-tris-acetylacetonate.

Executive summary:

The potential for adverse effects from 2,4-pentanedione vapour was investigated by exposing rats (whole body) for various periods to a statically generated vapour saturated atmosphere, and also by exposing rats for 4 h to differing concentrations of dynamically generated vapour. Necropsy of animals that died showed dark red lungs, mottled livers, and gas-filled gastrointestinal tracts. Animals that survived showed no gross pathological features. The LC50 values for acetylacetonate following inhalative exposure were 5.2 mg/L for female and 5.1 mg/L for male/female rats.

This result is also valid for the target substance vanadium-tris-acetylacetonate, since the source substance acetylacetonate is a hydrolysis product of vanadium-tris-acetylacetonate.

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

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

Adequacy of study:

weight of evidence

Justification for type of information:

please refer to Read-across statement attached in section 13

Reason / purpose for cross-reference:

read-across source

Mass median aerodynamic diameter (MMAD):

> <

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

7.9 mg/L air

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

7.3 mg/L air

Based on:

test mat.

Sex:

male

Dose descriptor:

other: No-effect level

Effect level:

2.2 mg/L air

Based on:

test mat.

Sex:

female

Dose descriptor:

other: No-effect level

Effect level:

3.6 mg/L air

Based on:

test mat.

Mortality:

Animals died up to 8 days after the inhalative exposure.

Other findings:

Histopathological examination of the lungs of the animals that received inhalative exposure revealed haemorrhage, vascular congestion and oedema in the lungs and bronchopneumonia

Calculation of LD50 of vanadium acetylacetonate:

EC(V) in source substance

Source substance NH4VO3

MW (NH4VO3) = 116.98 g/mol

MW (V) = 50.94 g/mol

V in NH4VO3 = 50.94 / 116.98 = 0.44

EC (V) = EC(NH4VO3) x 0.44 = 2.61 mg/L x 0.44 = 1.15 mg/L

EC of target substance vanadium acetylacetonate (VAA)

MW V in NH4VO3 = 50.94 g/mol

MW VAA = 348.27 g/mol

EC (VAA) in target = EC (V) in source / 50.94 x 348.27

EC (V) in source = 1.15 mg/L

EC (VAA) in target = 1.15 / 50.94 x 348.27 = 7.9 mg/L

The further values are calculated accordingly.

Interpretation of results:

other: according to CLP not classified (> 5 mg/L)

Conclusions:

The LC50 for ammonium vanadate is reported to be 2.61 and 2.43 mg/L for male rats and female rats, respectively. Those values correspond to a LC50 of 7.9 mg/L for male rats and to a LC50 of 7.3 mg/L for female rats for vanadium acetylacetonate.

Executive summary:

Rats were exposed to dust of ammonium vanadate (NH₄VO₃, CAS 7803 -55 -6) for 4 hours (nose only). Animals died up to 8 days after the inhalative exposure. Histopathological examination of the lungs of the animals that received inhalative exposure revealed haemorrhage, vascular congestion and oedema in the lungs and bronchopneumonia. The LC50-values for V₂O₃(analytical grade, powder) is 6.65 mg/L in female rats. The LC50-values for the NH₄VO₃ test-substance following inhalative exposure were 2.61 mg/L for male and 2.43 mg/L for female rats. These values correspond to a LC50 of 7.9 mg/L for male rats and to a LC50 of 7.3 mg/L for female rats for vanadium acetylacetonate

For details regarding the calculation path please see section “Any other information on results incl. tables”.

Reference 3

Endpoint:

acute toxicity: inhalation

Type of information:

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

Adequacy of study:

weight of evidence

Justification for type of information:

please refer to Read-across statement attached in section 13

Reason / purpose for cross-reference:

read-across source

Mass median aerodynamic diameter (MMAD):

> <

Sex:

male

Dose descriptor:

LC50

Remarks on result:

not determinable

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

> 30.9 mg/L air

Based on:

test mat.

Sex:

male

Dose descriptor:

other: No-effect level

Remarks on result:

not determinable

Sex:

female

Dose descriptor:

other: No-effect level

Effect level:

> 30.9 mg/L air

Based on:

test mat.

Mortality:

Animals died up to 8 days after the inhalative exposure.

Other findings:

Histopathological examination of the lungs of the animals that received inhalative exposure revealed haemorrhage, vascular congestion and oedema in the lungs and bronchopneumonia.

Calculation of LD50 of vanadium acetylacetonate:

EC(Mn) in source substance

Source substance V2O3

MW (V2O3) = 149.88 g/mol

MW (V) = 50.94 g/mol

V in V2O3 = (2*50.94) / 149.88 = 0.68

EC (V) = EC(V2O3) x 0.68 = 6.65 mg/L x 0.68 = 4.52 mg/L

EC of target substance vanadium acetylacetonate (VAA)

MW V in V2O3 = 2*50.94 g/mol

MW VAA = 348.27 g/mol

EC (VAA) in target = EC (V) in source / 50.94 x 348.27

EC (V) in source = 4.52 mg/L

EC (VAA) in target = 4.52 / 50.94 x 348.27 = 30.9 mg/L

The further values are calculated accordingly.

Interpretation of results:

GHS criteria not met

Conclusions:

The LC50 for vanadium trioxide is reported to be >6.65 mg/L for female rats, corresponding to a LC50 of >30.9 mg/L for female rats for vanadium acetylacetonate.

Executive summary:

Rats were exposed to dust of vanadium (III) oxide (V₂O₃, CAS 1314 -34 -7) for 4 hours (nose only). Animals died up to 8 days after the inhalative exposure. Histopathological examination of the lungs of the animals that received inhalative exposure revealed haemorrhage, vascular congestion and oedema in the lungs and bronchopneumonia. The LC50-values for V₂O₃(analytical grade, powder) is 6.65 mg/L in female rats.

This corresponds to a LC50 of >30.9 mg/L for vanadium acetylacetonate.

For details regarding the calculation path please see section “Any other information on results incl. tables”.

Reference 4

Endpoint:

acute toxicity: inhalation

Type of information:

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

Adequacy of study:

weight of evidence

Justification for type of information:

please refer to Read-across statement attached in section 13

Reason / purpose for cross-reference:

read-across source

Mass median aerodynamic diameter (MMAD):

> <

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

42.5 mg/L air

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

16.5 mg/L air

Based on:

test mat.

Sex:

male

Dose descriptor:

other: No-effect level

Effect level:

3.4 mg/L air

Based on:

test mat.

Sex:

female

Dose descriptor:

other: No-effect level

Effect level:

9.3 mg/L air

Based on:

test mat.

Mortality:

Animals died up to 8 days after the inhalative exposure.

Other findings:

Histopathological examination of the lungs of the animals that received inhalative exposure revealed haemorrhage, vascular congestion and oedema in the lungs and bronchopneumonia.

Calculation of LD50 of vanadium acetylacetonate:

EC(Mn) in source substance

Source substance V2O5

MW (V2O5) = 181.88 g/mol

MW (V) = 50.94 g/mol

V in V2O5 = (2*50.94) / 181.88 = 0.56

EC (V) = EC(V2O5) x 0.56 = 11.09 mg/L x 0.56 = 6.21 mg/L

EC of target substance vanadium acetylacetonate (VAA)

MW V in V2O5 = 2*50.94 g/mol

MW VAA = 348.27 g/mol

EC (VAA) in target = EC (V) in source / 50.94 x 348.27

EC (V) in source = 6.21 mg/L

EC (VAA) in target = 6.21 / 50.94 x 348.27 = 42.5 mg/L

The further values are calculated accordingly.

Interpretation of results:

GHS criteria not met

Conclusions:

The LC50 for vanadium pentoxide is reported to be 11.09 and 4.3 mg/l for male rats and female rats, respectively. Those values correspond to a LC50 of 42.5 mg/l for male rats and to a LC50 of 16.5 mg/l for female rats for vanadium acetylacetonate.

Executive summary:

Rats were exposed to dust of vanadium pentoxide (V₂O₅, CAS 1314 -62 -1) for 4 hours (nose only). Animals died up to 8 days after the inhalative exposure. Histopathological examination of the lungs of the animals that received inhalative exposure revealed haemorrhage, vascular congestion and oedema in the lungs and bronchopneumonia. The LC50-values for the V₂O₅test-substance (analytical grade, powder) were 11.09 mg/L for male and 4.3 mg/L for female rats.

These values correspond to a LC50 of 42.5 mg/l for male rats and to a LC50 of 16.5 mg/l for female rats for vanadium acetylacetonate.

For details regarding the calculation path please see section “Any other information on results incl. tables”.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 091 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

weight of evidence

Justification for type of information:

please refer to Read-across statement attached in section 13

Reason / purpose for cross-reference:

read-across source

Sex:

male

Dose descriptor:

LD50

Effect level:

1.41 mL/kg bw

Based on:

test mat.

95% CL:

> 0.8 - < 2.49

Sex:

female

Dose descriptor:

LD50

Effect level:

0.81 mL/kg bw

Based on:

test mat.

95% CL:

> 0.59 - < 1.12

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

1 381.8 mg/kg bw

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

793.8 mg/kg bw

Based on:

test mat.

Mortality:

Times to death ranged from 45 min to 1 day.

Clinical signs:

other: Signs of toxicity before death were dilated pupils within 15 to 30 min, convulsions in one animal at the highest dosage, and excess blood-stained saliva. Survivors at 1.0 mL/kg had dilated pupils and sailvation, with recovery by the first postexposure day

Gross pathology:

Necropsy of animals that died showed red mottled lungs, patchy congestion of tracheal mucosa, and a few stomachs with superficial black foci. There was no significant gross pathology in survivors.

Table 1: Dosages, mortalities and times to death for animals used to determine the acute percutaneous toxicity of 2,4 -pentanedione (acetylacetonate).

Dosage (mL/kg)	Mortalities (No. dead/no. dosed)		Time to death
	male	female
10.0	3/3	ND*	1-2 h
5.0	3/3	ND	1-24 h
2.0	4/5	5/5	2.5-24 h
1.0	1/5	4/5	3.5-24 h
0.5	0/5	0/5	-

*ND, not dosed

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Mortality occured at 45 min to 1 day after dosing. Derived LD50 values were 1381.8 mg/kg bw and 793.8 mg/kg bw for male and female rabbits, respectively. This result is also valid for the target substance vanadium-tris-acetylacetonate, since the source substance acetylacetonate is a hydrolysis product of vanadium-tris-acetylacetonate.

Executive summary:

In an acute dermal toxicity study similar to OECD Guideline 402, groups of New Zealand White rabbits (5/sex/group) were given a single dermal dose of the test substance acetylacetonate, at doses from 0.5 - 10 mL/kg and observed for 14 days. Mortality occured at 45 min to 1 day after dosing. Derived LD50 values were 1381.8 mg/kg bw and 793.8 mg/kg bw for male and female rabbits, respectively. This result is also valid for the target substance vanadium-tris-acetylacetonate, since the source substance acetylacetonate is a hydrolysis product of vanadium-tris-acetylacetonate.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

weight of evidence

Justification for type of information:

please refer to Read-across statement attached in section 13

Reason / purpose for cross-reference:

read-across source

Preliminary study:

not performed

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 7 520 mg/kg bw

Based on:

test mat.

Sex:

not specified

Dose descriptor:

other: no-effect level

Effect level:

> 7 520 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no signs of toxicity were observed

Mortality:

Mortality did not occur in treated animals.

Clinical signs:

other: No signs of toxicity were observed following dermal application.

Gross pathology:

not performed

Other findings:

No signs of toxicity were observed following dermal application.

Calculation of LD50 and NOEL of vanadium acetylacetonate:

EC(Mn) in source substance

Source substance NH4VO3

MW (NH4VO3) = 116.98 g/mol

MW (V) = 50.94 g/mol

V in NH4VO3 = 50.94 / 116.98 = 0.44

EC (V) = EC(NH4VO3) x 0.44 = 2500 mg/kg bw x 0.44 = 1100 mg/kg bw

EC of target substance vanadium acetylacetonate (VAA)

MW V in NH4VO3 = 50.94 g/mol

MW VAA = 348.27 g/mol

EC (VAA) in target = EC (V) in source / 50.94 x 348.27

EC (V) in source = 1100 mg/kg bw

EC (VAA) in target = 1100 / 50.94 x 348.27 = 7520 mg/kg bw

Interpretation of results:

GHS criteria not met

Conclusions:

No mortality occurred at a tested level of 2500 mg NH4VO3/kg bw. The LD50 is considered to be more than 2500 mg/kg bw. Converted to the target substance vanadium-tris-acetylacetonate this corresponds to a LD50 and NOEL of >7520 mg/kg bw.

Executive summary:

In an acute dermal toxicity study, groups of Sprague-Dawley rats (5/group) were given a single dermal dose of ammonium metavanadate, at 2500 mg/kg bw and observed for 14 days. No mortality occurred in this test; therefore an exact LD50 has not been determined. The test article, when administered dermally as received to 5 Sprague Dawley rats had an acute dermal LD50 of greater than 2.5 g/kg bw. No evidence of systemic toxicity was observed. Converted to the target substance vanadium-tris-acetylacetonate this corresponds to a LD50 and NOEL of >7520 mg/kg bw.

For details regarding the calculation path please see section “Any other information on results incl. tables”.

Reference 3

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

weight of evidence

Justification for type of information:

please refer to Read-across statement attached in section 13

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 11 622.7 mg/kg bw

Based on:

test mat.

Sex:

not specified

Dose descriptor:

other: no-effect level

Effect level:

> 11 622.7 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no signs of toxicity were observed

Mortality:

Mortality did not occur in treated animals.

Clinical signs:

other: No signs of toxicity were observed following dermal application.

Gross pathology:

not performed

Other findings:

No signs of toxicity were observed following dermal application.

Calculation of LD50 and NOEL of vanadium acetylacetonate:

EC(Mn) in source substance

Source substance V2O3

MW (V2O3) = 149.88 g/mol

MW (V) = 50.94 g/mol

V in V2O3 = (2*50.94) / 149.88 = 0.68

EC (V) = EC(V2O3) x 0.68 = 2500 mg/kg bw x 0.68 = 1700 mg/kg bw

EC of target substance vanadium acetylacetonate (VAA)

MW V in V2O3 = 2*50.94 g/mol

MW VAA = 348.27 g/mol

EC (VAA) in target = EC (V) in source / 50.94 x 348.27

EC (V) in source = 1700 mg/kg bw

EC (VAA) in target = 1700 / 50.94 x 348.27 = 11622.7 mg/kg bw

Interpretation of results:

GHS criteria not met

Conclusions:

No mortality occurred at a tested level of 2500 mg V2O3/kg bw. The LD50 is considered to be more than 2500 mg/kg bw. Converted to the target substance vanadium-tris-acetylacetonate this corresponds to a LD50 and NOEL of >11622.7 mg/kg bw.

Executive summary:

In an acute dermal toxicity study (limit test similar to OECD Guideline 402), groups of Sprague-Dawley rats (5/group) were given a single dermal dose of vanadium trioxide at 2500 mg/kg bw and observed for 14 days. No mortality occurred in this test; therefore an exact LD50 has not been determined. The test article vanadium trioxide, when administered dermally as received to 5 Sprague Dawley rats had an acute dermal LD50 of greater than 2.5 g/kg bw. No evidence of systemic toxicity was observed. Converted to the target substance vanadium-tris-acetylacetonate this corresponds to a LD50 and NOEL of >11622.7 mg/kg bw. For details regarding the calculation path please see section “Any other information on results incl. tables”.

Reference 4

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

weight of evidence

Justification for type of information:

please refer to Read-across statement attached in section 13

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 9 571.6 mg/kg bw

Based on:

test mat.

Sex:

not specified

Dose descriptor:

other: no-effect level

Effect level:

> 9 571.6 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no signs of toxicity were observed

Mortality:

Mortality did not occur in treated animals.

Clinical signs:

other: No signs of toxicity were observed following dermal application.

Other findings:

No signs of toxicity were observed following dermal application.

Calculation of LD50 and NOEL of vanadium acetylacetonate:

EC(Mn) in source substance

Source substance V2O5

MW (V2O5) = 181.88 g/mol

MW (V) = 50.94 g/mol

V in V2O5 = (2*50.94) / 181.88 = 0.56

EC (V) = EC(V2O5) x 0.56 = 2500 mg/kg bw x 0.56 = 1400 mg/kg bw

EC of target substance vanadium acetylacetonate (VAA)

MW V in V2O5 = 2*50.94 g/mol

MW VAA = 348.27 g/mol

EC (VAA) in target = EC (V) in source / 50.94 x 348.27

EC (V) in source = 1400 mg/kg bw

EC (VAA) in target = 1400 / 50.94 x 348.27 = 9571.6 mg/kg bw

Interpretation of results:

GHS criteria not met

Conclusions:

No mortality occurred at a tested level of 2500 mg V2O5/kg bw. The LD50 is considered to be more than 2500 mg/kg bw. Converted to the target substance vanadium-tris-acetylacetonate this corresponds to a LD50 and NOEL of >9571.6 mg/kg bw.

Executive summary:

In an acute dermal toxicity study (limit test similar to OECD Guideline 402), groups of Sprague-Dawley rats (5/group) were given a single dermal dose of vanadium pentoxide, at 2500 mg/kg bw and observed for 14 days. No mortality occurred in this test; therefore an exact LD50 has not been determined. The test article vanadium pentoxide, when administered dermally as received to 5 Sprague Dawley rats had an acute dermal LD50 of greater than 2.5 g/kg bw. No evidence of systemic toxicity was observed. Converted to the target substance vanadium-tris-acetylacetonate this corresponds to a LD50 and NOEL of >9571.6 mg/kg bw.

For details regarding the calculation path please see section “Any other information on results incl. tables”.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

793.8 mg/kg bw

Additional information

2,4 -pentanedione

oral

The acute toxicity of 2,4 -pentanedione (CAS 123 -54 -6) was studies similar to OECD Guideline 401 in rats. The test item was applied orally (by gavage) in 5 concentrations ranging from 0.25 to 1 mL/kg bw. Following oral administration, signs of toxicity observed at doses of 0.5 mL/kg included sluggish and unsteady gait by 30 min, prostation and lachrymation by 1.5 to 2 h, and tremor, twitching movements and convulsion at 2 to 3 h. Bodyweight was unaffected in survivors and no gross pathology changes were seen in animals that died or sacrificed survivors. The LD50 values were 760 mg/kg bw for male and 578 mg/kg bw for female rats (Ballantyne 1986).

inhalation

The potential for adverse effects from 2,4-pentanedione vapour was investigated by exposing rats (whole body) for various periods to a statically generated vapour saturated atmosphere, and also by exposing rats for 4 h to differing concentrations of dynamically generated vapour. Necropsy of animals that died showed dark red lungs, mottled livers, and gas-filled gastrointestinal tracts. Animals that survived showed no gross pathological features. The LC50 values for acetylacetonate following inhalative exposure were 5.2 mg/L for female and 5.1 mg/L for male/female rats

dermal

In an acute dermal toxicity study similar to OECD Guideline 402, groups of New Zealand White rabbits (5/sex/group) were given a single dermal dose of the test substance acetylacetonate, at doses from 0.5 - 10 mL/kg and observed for 14 days. Mortality occured at 45 min to 1 day after dosing. Derived LD50 values were 1381.8 mg/kg bw and 793.8 mg/kg bw for male and female rabbits, respectively.

Vanadium compounds

Hazard values of the vanadium containing source substances were converted to the target substance vanadium acetylacetonate. The hazard values for vanadium acetylacetonate were calculated as follows:

Effect concentration of vanadium in source substance (EC (V))

MW (source substance) = 116.98 g/mol

MW (Vanadium) = 50.94 g/mol

ratio of vanadium in source substance = n* 50.94 / MW (source substance)

EC (V) = EC(source substance) x ratio of vanadium in source substance

Effect concentraion of target substance vanadium acetylacetonate (VAA)

MW V in VAA = 50.94 g/mol

MW VAA = 348.27 g/mol

EC (VAA) in target = EC (V) in source / 50.94 x 348.27

oral

The acute oral toxicity of vanadium pentoxide (V₂O₅, CAS 1314 -62 -1), vanadium (III) oxide (V₂O₃, CAS 1314 -34 -7) and ammonium vanadate (NH₄VO₃, CAS 7803 -55 -6) was studies similar to OECD Guideline 401. Following administration, observations were made and recorded systematically with individual records being maintained for each animal. Observations were performed immediately, 5, 15, 30 and 60 min, as well as 3 h, 6 h and 24 h after administration. Then twice daily for a period of 14 days. The time of death was recorded as precisely as possible. Individual body weights were recorded before administration of the substance, thereafter in weekly intervals up to the end of the study, and at death. At the end of the experiments all surviving animals were sacrificed, dissected and inspected macroscopically. All gross pathological changes were recorded. Autopsy and macroscopic inspection of rats which died prematurely were carried out as soon as possible after exitus.

The following results were derived:

The LD50 for vanadium pentoxide (V₂O₅) is 470 mg/kg bw for male rats and 467 mg/kg bw for female rats. These values correspond to an LD50 of 1799.5 mg/kg bw for male rats and to a LD50 of 1788.0 mg/kg bw for female rats for vanadium acetylacetonate.

The LD50-values for vanadium oxide (V₂O₃) is 8713 mg/kg for male and 5639 mg/kg for female rats. These values correspond to a LD50 of 40507 mg/kg bw for male rats and to a LD50 of 26216 mg/kg bw for female rats for vanadium acetylacetonate.

The LD50 for ammonium vanadate (NH₄VO₃) is 218 and 141 mg/kg bw for male rats and female rats, respectively. These values correspond to a LD50 of 655.8 mg/kg bw for male rats and to a LD50 of 424.2 mg/kg bw for female rats for vanadium acetylacetonate.

inhalation

Rats were exposed to dust of vanadium pentoxide (V₂O₅, CAS 1314 -62 -1) for 4 hours (nose only). Animals died up to 8 days after the inhalative exposure. Histopathological examination of the lungs of the animals that received inhalative exposure revealed haemorrhage, vascular congestion and oedema in the lungs and bronchopneumonia. The LC50-values for the V₂O₅ test-substance (analytical grade, powder) were 11.09 mg/L for male and 4.3 mg/L for female rats. These values correspond to a LC50 of 42.5 mg/l for male rats and to a LC50 of 16.5 mg/l for female rats for vanadium acetylacetonate.

Rats were exposed to dust of vanadium (III) oxide (V₂O₃,CAS 1314 -34 -7) for 4 hours (nose only). Animals died up to 8 days after the inhalative exposure. Histopathological examination of the lungs of the animals that received inhalative exposure revealed haemorrhage, vascular congestion and oedema in the lungs and bronchopneumonia. The LC50-values for V₂O₃ (analytical grade, powder) is > 6.65 mg/L in female rats

This corresponds to a LC50 of >30.9 mg/L for vanadium acetylacetonate.

Rats were exposed to dust of ammonium vanadate (NH₄VO₃, CAS 7803 -55 -6) for 4 hours (nose only). Animals died up to 8 days after the inhalative exposure. Histopathological examination of the lungs of the animals that received inhalative exposure revealed haemorrhage, vascular congestion and oedema in the lungs and bronchopneumonia. The LC50-values for V₂O₃(analytical grade, powder) is 6.65 mg/L in female rats. The LC50-values for the NH₄VO₃test-substance following inhalative exposure were 2.61 mg/L for male and 2.43 mg/L for female rats. These values correspond to a LC50 of 7.9 mg/L for male rats and to a LC50 of 7.3 mg/L for female rats for vanadium acetylacetonate.

dermal

In acute dermal toxicity studies (limit test similar to OECD Guideline 402), groups of Sprague-Dawley rats (5/group) were given a single dermal dose of vanadium pentoxide, vanadium oxide and ammonium vanadate at 2500 mg/kg bw and observed for 14 days. No mortality occurred in these tests; therefore exact LD50 have not been determined. The test articles vanadium pentoxide, vanadium oxide and ammonium vanadate when administered dermally as received to 5 Sprague Dawley rats had an acute dermal LD50 of greater than 2.5 g/kg bw. No evidence of systemic toxicity was observed.

Justification for classification or non-classification

Based on the available data on the vanadium source substances and acetylacetonate, the target substance vanadium-tris-acetylacetonate is classified as acute toxic - oral (Category 4, H302), acute toxic - inhalation (Category 3, H331) and acute toxic - dermal (Category 3, H311) in accordance with Regulation (EC) No 1272/2008.