Benzenamine, N,N-dimethyl-, oxidized, molybdatetungstatephosphates

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral, other

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29 Aug 2017 - 22 Feb 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Benzenamine, N,N-dimethyl-, oxidized, molybdatetungstatephosphates

EC Number:

309-916-8

EC Name:

Benzenamine, N,N-dimethyl-, oxidized, molybdatetungstatephosphates

Cas Number:

101357-19-1

Molecular formula:

Reaction mass of C25 H30 N3. P Moy Wz O40 (y +z = 12) , C24 H28 N3. P Moy Wz O40 (y +z = 12) and C23 H26 N3. P Moy Wz O40 (y +z = 12)

IUPAC Name:

Reaction mass of [4-[bis[4-(dimethylamino)phenyl]methylene]cyclohexa-2,5-dien-1-ylidene]-dimethyl-ammonium. molybdatetungstatephosphates, [4-[[4-(dimethylamino)phenyl]-[4-(methylamino)phenyl]methylene]cyclohexa-2,5-dien-1-ylidene]-dimethyl-ammonium. molybdatetungstatephosphates and [4-[bis[4-(methylamino)phenyl]methylene]cyclohexa-2,5-dien-1-ylidene]-dimethyl-ammonium. molybdatetungstatephosphates

Test material form:

solid: nanoform, no surface treatment

Details on test material:

SOURCE OF TEST MATERIAL
-Product number: 0345N (skin sensitisation, OECD 422, eye irritation, acute oral toxicity)
0345F (Ames test)

- Purity Preparation containing ≥80% (treat as 100%)
- Physical form/colour: Violet powder
- Expiry date: Stable for at least 5 years from delivery date

-Shape Category: spheroidal
-Shape: spherycal
-pure shape: yes
-Typical composition: ca. 100%
-range >50 and < 100%

-D10, typical value: 30 nm, range: >1.5 and < 50nm
-D50, typical value: 45 nm, range: >15 and <100nm
-D90, typical value: 60nm, range: >25 and < 150nm

-Fraction in size range 1-100nm: > 50 and <100%

-Crystallinity:
Structure:
amorphous, pure structure

-SSA: BET surface area typically ca. 32-40 m2/g for product number 345F and 0345N)
Range > 10 and < 200 m2/g

-.no surface treatment

Storage conditions: Stored at ambient conditions in the dark (away from direct light)
- Safety precautions: Routine hygienic procedures (nitrile gloves, goggles, face mask)

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 10 weeks
- Weight at study initiation: Males: 331-431 g Females: 179-245 g
- Housing: Cages with standard, granulated, S8-15 sawdust bedding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30 - 70
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/ 12

Administration / exposure

Route of administration:

oral: gavage

Details on route of administration:

Oral, by gastric gavage. For each dose group the order of administration was all males first and then all females. Each day of treatment the starting order was alternated between males and females.

Vehicle:

arachis oil

Details on oral exposure:

- VEHICLE
- Batch number KMO9422, KM09047
- Expiry date: August 2018
- Storage conditions: Stored at ambient conditions
- Safety precautions: Routine hygienic procedures (nitrile gloves, goggles, face mask)

- Concentration in vehicle: 0, 100, 300 and 1000 mg/kg/day
- Administration volume: 5 mL/kg

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Validation done at 20-200 mg/mL demonstrates that formulations were stable for 8 days at room temperature (20 ± 5 ºC) and in the dark.

The results showed that analyzed formulations were within 19% of their nominal concentration. The coefficient of variation (CV) was not more than 2.13%. Preparation of all formulations was considered correct, taking into account the acceptance ranges.

The analysis of control group formulations showed that no contamination was present.

Duration of treatment / exposure:

5 - 8 weeks

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

100 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

300 mg/kg bw/day (nominal)

Doses / concentrations 4

Dose / conc.:

1 000 mg/kg bw/day (nominal)

No. of animals per sex per dose:

3 groups of 12 females
3 gouprs of 12 males
1 control group of 12 females
1 control group of 12 males

Control animals:

yes

Examinations

Observations and examinations performed and frequency:

VIABILITY/ MORTALITY/ CAGE-SIDE OBSERVATIONS
Visually inspected twice daily for evidence of reaction to treatment or ill-health.

BODY WEIGHT:
- Time schedule for examinations: On day 1 and weekly thereafter

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

no effects observed

Water consumption and compound intake (if drinking water study):

no effects observed

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not specified

Behaviour (functional findings):

no effects observed

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

effects observed, non-treatment-related

Description (incidence and severity):

The changes observed in the brain weights in males and females and in liver weights in males at 1000 mg/kg/day when compared to control were considered incidental taking into account the magnitude of the change, the lack of a dose-effect relationship and that there was no correlation with clinical pathology or histopathology.

Gross pathological findings:

no effects observed

Neuropathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Other effects:

not specified

Effect levels

Key result

Dose descriptor:

NOEL

Effect level:

ca. 1 000 mg/kg diet

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

clinical signs

food consumption and compound intake

other: clinical pathology, organ weights or histopathology

Target system / organ toxicity

Key result

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

The No Observed Effect Level (NOEL) for systemic toxicity was considered to be 1000 mg/kg/day, taking into account that there was no effect on body weight, food consumption, clinical signs, clinical pathology, organ weights or histopathology.