[1,3-dihydro-5,6-bis[[(2-hydroxy-1-naphthyl)methylene]amino]-2H-benzimidazol-2-onato(2-)-N5,N6,O5,O6]nickel

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2021

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2022

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

2009

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

traditional method

Limit test:

yes

Test material

Test material information

1

Reference substance name:

[1,3-dihydro-5,6-bis[[(2-hydroxy-1-naphthyl)methylene]amino]-2H-benzimidazol-2-onato(2-)-N5,N6,O5,O6]nickel

EC Number:

255-965-2

EC Name:

[1,3-dihydro-5,6-bis[[(2-hydroxy-1-naphthyl)methylene]amino]-2H-benzimidazol-2-onato(2-)-N5,N6,O5,O6]nickel

Cas Number:

42844-93-9

Molecular formula:

C29H18N4NiO3

IUPAC Name:

Nickel, [1,3-dihydro-5,6-bis[[[2-(hydroxy-kO)-1-naphthalenyl]methylene]amino-kN]-2H-benzimidazol-2-onato(2-)]-, (SP-4-2)-

Test material form:

solid: nanoform

Test animals

Species:

rat

Sex:

male/female

Details on test animals or test system and environmental conditions:

Male and female Crl:WI Wistar rats (from SPF colony) were obtained from Charles River Laboratories, Research Models and Services, Germany GmbH (Sandhofer Weg 7,
D-97633 Sulzfeld, Germany).
After arrival, the animals’ health was certified by the Veterinarian.
Species and strain: Crl:WI Wistar rats
Hygienic level: SPF at arrival, standard housing conditions during the study
Number of animals: Sighting Exposure: 1 animal/sex
Main Study: 5 animals/sex
Sex: Male and female, females: non-pregnant and nulliparous
Age and body weight range of animals on the exposure day (Day 0) were:
Sighting Exposure: 8 weeks old, 314 g (males) and 217 g (females)
Main Study: 9 weeks old, 348-372 g (males) and 240-252 g (females

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

ca. 3.04 - ca. 3.59 µm

Geometric standard deviation (GSD):

ca. 2.42

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

ca. 4 h

Concentrations:

5.02 - 5.06 mg/L

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

guideline study

Statistics:

Data were collected using the software PROVANTIS v.10 or were recorded on data collection sheets taken from the relevant SOPs, then tabulated using PROVANTIS v.10, Microsoft Office Word and/or Excel, as appropriate.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC0

Effect level:

ca. 5.02 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

none

Clinical signs:

irregular respiration

Remarks:

laboured breathing (slight), fur staining by test item (red, on the cranium, face and whole body) and wet fur (generalized) were observed, but the breathing symptoms could be observed on Days 0-1 only.

Body weight:

no effects

Gross pathology:

no effects

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

No mortality occurred when exposed to a test atmosphere concentration of 5.02 mg/L as a maximum achievable concentration for 4 hours. The acute inhalation median lethal concentration (LC50) of PV Fast Orange 6RL in male and female Crl:WI rats was therefore considered to be above 5.02 mg/L

Executive summary:

Crl:WI Wistar strain rats were exposed to test atmosphere of PV Fast Orange 6RL at the target concentration of 5 mg/mL. An atmosphere was generated from the test item as supplied.

A Sighting Exposure was performed first; the target concentration (5 mg/L) was tested on one animal each of both sexes (Group 0.1).

Based on the results of the Sighting Exposure (Group 0.1), the Main Study was performed at the target concentration (5 mg/L). Five male and five female rats were used in the Main Group (Group 1).

In the study, the animals were exposed to the test atmosphere for 4 hours using a nose-only exposure system. Aerosol concentration was measured gravimetrically
17 times during each 4-hour exposure. The particle size distribution of the test aerosol was determined 3 times. The day of exposure was designated as Day 0 followed by a 14-day observation period.

Clinical observations were performed on all animals during exposure at hourly intervals, following removal from restraint, approximately 1 hour after exposure, and daily for 14 days thereafter. Body weight was measured on Days 0 (before the exposure), 1, 3, 7 and 14. Gross necropsy was performed on all animals on Day 14.

No control group was exposed in this study.

The quality of the test atmosphere fully complied with criteria documented in the respective guidelines: OECD 403, EPA OPPTS 870.1300 and Council Regulation (EC) No 440/2008.

The mean achieved atmosphere concentrations in the study were 5.06 and 5.02 mg/L in Group 0.1 and Group 1, respectively. The mass median aerodynamic diameters (MMAD) were 3.59 and 3.04 µm with geometric standard deviations (GSD) of 2.42 and 2.61 in Group 0.1 and Group 1, respectively.

Summary of the test atmosphere parameters

Group Number	Target Concentration (mg/L)	Mean Achieved Concentration (mg/L)	Standard Deviation of Achieved Concentration (mg/L)	MMAD (µm) / GSD
Sighting Exposure
0.1	5	5.06	0.17	3.59 / 2.42
Main Study
1	5	5.02	0.16	3.04 / 2.61

 

 Mortality

No mortality occurred during the study.

Clinical observations

Sighting Exposure (Group 0.1 - 5.06 mg/L)

Laboured breathing (slight to moderate), abnormal breathing sounds, red fur staining (by test item, on the cranium, generalized) and wet fur (generalized) were observed. Fur staining was observed during the whole observation period but the breathing symptoms were observed on Day 0 only.

Main Group (Group 1 - 5.02 mg/L)

In the male animals, laboured breathing (slight), fur staining by test item (red, on the cranium, face and whole body) and wet fur (generalized) were observed, but the breathing symptoms could be observed on Days 0-1 only.

In the female animals, laboured breathing (slight), fur staining by test item (red, on the cranium, face and whole body) and wet fur (on the whole body) were observed, but the breathing symptoms could be observed on Days 0 only.

Wet fur and fur staining in the animals were considered to be related to the restraint and exposure procedures but not to be toxicologically significant.

Summary of acute inhalation toxicity

Group Number	Mean Achieved Concentration (mg/L)	Toxicological Result*	Onset and Duration of Toxicological Clinical Signs (Day)	Occurrence of Mortality (Day)
Sighting Exposure
0.1	5.06	0/ 2/ 2	0	-
Main Study
1	5.02	0/ 10/ 10	0-1	-

* 1^st = number of dead animals, 2^nd = number of animals with signs, 3^rd = number of animals exposed

Body weight

Sighting Exposure (Group 0.1 – 5.05 mg/L)

In one male animal, slight body weight loss was noted on Days 0-1. The body weight gain was normal between Days 1-14.

Main Group (Group 1 – 5.02 mg/L)

Slight body weight loss was recorded on Days 0-1. The body weight gains were normal afterwards.

Necropsy

There was no evidence of any test item-related gross changes at necropsy in any animal.