2-Butenedioic acid (2Z)-, reaction products with ammonium di-.mu.3-hydroxyhexacosa-.mu.-oxododecaoxododecatungstate(6-) (6:1), ammonium octa-.mu.-oxodi-.mu.3-oxodi-.mu.4-oxododecaoxoheptamolybdate(6-) (6:1), nickel(2+) nitrate (1:2) and nickel(2+) sulfate (1:1)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09 - 30 May 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

GROUPE INTERMINISTERIEL DES PRODUITS CHIMIQUES

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

dioxomolybdenum; oxonickel; trioxotungsten

EC Number:

800-777-3

Cas Number:

1351378-24-9

Molecular formula:

(Ni)z(Mo)x(W)yO(13 – 20)x

IUPAC Name:

dioxomolybdenum; oxonickel; trioxotungsten

Test material form:

other: grains

Details on test material:

- Name of test material (as cited in study report): 2-Butenedioic acid (2Z)-, reaction products with ammonium di-µ3-hydroxyhexacosa-µ-oxododecaoxododecatungstate(6-) (6:1), ammonium octa-µ-oxodi-µ3-oxo-µ4-oxododecaoxoheptamolybdate(6-) (6:1), nickel(2+) nitrate (1:2) and nickel(2+) sulfate (1:1)
- Physical state: green grains
- Analytical purity: > 99%
- Lot/batch No.: 19266-184-1
- Expiration date of the lot/batch: May 2018
- Storage condition of test material: at room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage JANVIER, Le Genest St Isle, France
- Age at study initiation: 8 - 9 weeks
- Weight at study initiation: 183 - 231 g
- Fasting period before study: animals were fasted one day prior to substance administration until 4 hrs after substance administration (diet only).
- Housing: 3 animals per cage in solid-bottomed clear polycarbonate cages with stainless steel mesh lids
- Diet: M20 (pelleted), Specific Diet Services, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle:
2000 mg/kg bw: 200 mg/mL
300 mg/kg bw: 30 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

3 (controls), 12 (test substance group; 3 animals per step in a two-step testing procedure with 2 concentrations)

Control animals:

other: 3 animals received 10 mL/kg bw olive oil via gavage in a current control study performed from 14 Feb - 28 Feb 2012

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed 0.5, 1, 3 and 4 h after substance administration and daily thereafter and individual body weights were determined periodically on day 0 (prior to substance administration), 2, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, other: macroscopical examination of oesophagus, stomach, duodenum, jejunum, ileon, caecum, colon, rectum, spleen, liver, thymus, trachea, lungs, heart, kidneys, urinary bladder, ovaries, uterus, adrenals and pancreas

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

1 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 cut-off according to OECD 423

Mortality:

2000 mg/kg bw: In the first step, 2/3 animals died (2 or 4 days after substance application); in the second step, 3/3 rats died (Day 2, 3 and 4)

300 mg/kg bw: No mortality was observed during the study period.

For details, please refer to Table 1 under "Any other information on results".

Clinical signs:

other: 2000 mg/kg bw: Mortalities were preceded by a decrease in muscle tone and piloerection in 2/5 and 5/5 rats, respectively. The surviving high-dose animal showed piloerection after dosing. 300 mg/kg bw: Decreased spontaneous activity and piloerection was o

Gross pathology:

2000 mg/kg bw: Non-surviving animals: Rigor mortis was noted before necropsy in 5/5 animals. Marked lysis preventing macroscopical examinations was observed in 3/5 animals. Examination of the other animals revealed thinning of the forestomach in 1/5 animals with red coloration, black coloration of the forestomach, black coloration of the corpus (1/5) and thinning of the corpus (2/5).

Surviving animals: The surviving high-dose animal revealed a thickening of the forestomach.

300 mg/kg bw: Macroscopical examinations revealed no substance-related findings.

Any other information on results incl. tables

Table 1. Mortality and clinical signs after test substance administration.

 

Dose [mg/kg bw]	Toxicological results*	Duration of clinical signs	Time of death	Mortality (%)
Females
300	3/2/6	0.5 – 3 h	---	0
2000	5/6/6	0.5 h - Day 3	Day 2, Day 3 + Day 4	83%
LD50 cut off = 1000 mg/kg bw

                                                                                           

* first number = number of dead animals                                 

 second number = number of animals with clinical signs         

 third number = number of animals used         

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: Acute Oral 4, H302
DSD: Xn, R22