Manganese, 3-hydroxy-4-[(1-sulfo-2-naphthalenyl)azo]-2-naphthalenecarboxylic acid complex

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

The inhalation route of administration was selected because this route was defined as a possible route of human exposure.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

September 2009

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Version / remarks:

August 1998

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: EC No 440/2008, part B. Acute Toxicity (inhalation)

Version / remarks:

May 2008

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF, Appendix to Director General Notification, No. 12-Nousan-8147

Version / remarks:

November 2000

Deviations:

no

GLP compliance:

yes

Test type:

traditional method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Calcium 3-hydroxy-4-[(1-sulphonato-2-naphthyl)azo]-2-naphthoate

EC Number:

229-142-3

EC Name:

Calcium 3-hydroxy-4-[(1-sulphonato-2-naphthyl)azo]-2-naphthoate

Cas Number:

6417-83-0

Molecular formula:

C21H12N2O6S.Ca

IUPAC Name:

calcium 3-hydroxy-4-[(1-sulfonato-2-naphthyl)diazenyl]-2-naphthoate

Test material form:

solid: particulate/powder

Details on test material:

- Physical appearance: red powder
- Storage conditions: at room temperature

Specific details on test material used for the study:

Before use the test item was grinded with an automatic grinder and passed through a 355 µm steel mesh sieve.

Test animals

Species:

rat

Strain:

other: Crl:WI(Han)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: appr. 9 weeks
- Females were nulliparous and non-pregnant: yes
- Weight at study initiation: 289 - 317 g (males); 186 - 198 g (females)
- Fasting period before study: no
- Housing: group housing of maximally 5 animals of the same sex and same exposure group in polycarbonate Makrolon cages containing sterilized sawdust as bedding material.
- Diet: pelleted rodent diet (SM R/M-Z from SNIFF Spezialdiäten GmbH, Soest, Germany), ad libitum (no access to food during exposure)
- Water: tap water, ad libitum (no access to water during exposure)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Humidity (%): 50-69
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

> 3.7 - < 4 µm

Geometric standard deviation (GSD):

> 2 - < 2.3

Remark on MMAD/GSD:

The are analytically verified value for the MMAD and GSD.

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:flow past nose-only inhalation chamber (Am. Ind. Hyg Assoc. J. 44(12): 923-928, 1983)
- Method of holding animals in test chamber: restraining tubes
- Rate of air: at least 1 L/min (theoretical air flow in each animal port); mean total airflow: 22 L/min
- System of generating particulates/aerosols: Administering the test item to a stream of pressurized air using a combination of a spiral feeder and micronizing jet mill generated an aerosol. The aerosol was passed through a series of two cyclones, allowing larger particles to settle, before it entered the exposure chamber.
- Method of particle size determination: The particle size distribution was characterized twice during each exposure period. The samples were drawn with a flow of 2 L/min. from the test atmosphere through a tube mounted in one of the free animal ports of the exposure chamber. The samples were collected with an 8 stage Marple personal cascade impactor containing fiber glass filters and a fiber glass back-up filter. Amounts of test item collected were measured gravimetrically. Subsequently the time-weighted mean concentration with the standard deviation was calculated.
- Treatment of exhaust air: filtered and released to the exhaust of the fume hood.
- Temperature, humidity in air chamber: 22.7-23.6°C; 15-20%

TEST ATMOSPHERE
- Brief description of analytical method used: It was considered that the opacity of the test atmosphere could not be reliably monitored by means of an aerosol monitoring system. An indication of stability of the test atmosphere was obtained from the concentration measurements equally distributed over time. The nominal concentration was calculated by dividing the amount of test item used by the volume of pressurized air (average air flow times exposure time) entering the exposure chamber used for exposure of the animals. Due to the small volume of the exposure chamber the equilibrium time was negligible. The volume of air was calculated from the average air flow (which was measured by means of thermal mass flow meters and recorded regularly, preferably in 30 minute intervals) and the exposure time.
- Samples taken from breathing zone: yes, a total of 18 representative samples was taken during exposure at 5 mg/L.

CLASS METHOD
- Rationale for the selection of the starting concentration: Based on the cut off concentration values specified in the UN and EC classification guidelines.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

5 mg/L

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Three times during exposure (mortality, signs of distress and effects on respiration); after exposure twice daily for mortality and clinical signs were observed one and three hours after exposure (day 1), and once daily thereafter. Body weight determined on days 1 (pre-administration), 2, 4, 8 and 15.
- Necropsy of survivors performed: yes

Statistics:

No statistical analysis was performed (the method used was not intended to calculate a LC50 value).

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality occurred.

Clinical signs:

other: During exposure, slow breathing and/or laboured breathing was seen for all animals. lethargy, hunched posture, laboured respiration were observed in all animals. Animals recovered from the clinical signs at day 4 and 5.

Body weight:

Overall body weight gain in males and females was within the range expected for rats of this strain and age used in this type of study.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Other findings:

Red staining of the animals was noted throughout the observation period and was considered to be due to the staining properties of the test item and therefore not toxicologically relevant.

Any other information on results incl. tables

TEST ATMOSPHERE: see table 1

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

An acute inhalation toxicity study with male and female rats was performed according OECD test guideline 403 and GLP principles. Based on the absence of mortality at a concentration of 5 mg/L in male and female rats, the substance is not classified for acute inhalation toxicity according to GHS and Regulation (EC) No. 1272/2008.

Executive summary:

An acute inhalation toxicity study was performed according OECD test guideline 403 and GLP principles with male and female rats. The test concentration was analyzed to be approximately 5 mg/L. During exposure, slow breathing and/or laboured breathing was seen for all animals.

Lethargy, hunched posture, laboured respiration were observed in all animals. Animals recovered from the clinical signs at day 4 and 5. No mortality was seen during exposure or during the 14 day observation period. Red staining of the animals was noted throughout the observation period and was considered to be due to the staining properties of the test item and therefore not toxicologically relevant. Overall body weight gain in males and females was within the range expected for rats of this strain and age used in this type of study. No abnormalities were found at macroscopic post mortem examination of the animals.