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

Endpoint summary

Description of key information

Two acute oral toxicity studies in rats were performed, both resulting in LD50 values of >5000 mg/kg bw.

An acute inhalation study was performed, the results show that PR63:1 is not acutely toxic after inhalation (LC50 > 5 mg/L).

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:

experimental study

Adequacy of study:

key study

Study period:

1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP, non-guideline study, predates implementation of GLP and/or development of study guidelines, restrictions in design and/or reporting but otherwise adequate for assessment.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Remarks:

body weights not recorded. Highest dose 5000 mg/kg bw

GLP compliance:

no

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: bred on premises
- Age at study initiation: 7-8 weeks
- Weight at study initiation: male 292g and female 201g
- Fasting period before study: 18 hours
- Housing: single
- Diet: commercial pelleted diet (Oakes Special Diet with added Vit. E) ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±2
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: polyethyleneglycol/water 50:50

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 17%

MAXIMUM DOSE VOLUME APPLIED: 30 mL/kg

Doses:

5 g/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: deaths and clinical signs

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred.

Clinical signs:

other: No clinical symptoms were recorded.

Gross pathology:

At autopsy no changes caused by the test substance were seen.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on an acute oral toxicity study in rats, the oral LD50 of Compound TK 11736 (CAS 6417-83-0) was found to exceed 5000 mg/kg bw/day.

Executive summary:

In an acute oral toxicity study male and female Sprague-Dawley rats were administered the test substance at a dose level of 5000 mg/kg bw (5 animals per sex per dose group) by oral gavage. Polyethylene glycol/water (50:50) was used as vehicle. Dosing was followed by a 14 day observation period. No clinical symptoms were recorded and no deaths occurred. At autopsy no changes were seen. Therefore the LD50 of Compound TK 11736 (CAS 6417-83-0) is > 5000 mg/kg bw.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions mostly due to reduced reporting.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Mean weight at study initiation: males 229 g; females 170 g

ENVIRONMENTAL CONDITIONS
not reported

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50 % suspension in 0.5 % aqueous CMC solution
- Maximum amount of vehicle (if gavage): 10 ml/kg bw, males: 2.2 ml; females: 1.7 ml

Doses:

5000 mg/kg bw.

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Weighing was only performed at the beginning of the study for dose calculation. Observation of clinical signs was several times on the day of administration and once daily afterwards with the exception of weekends and on holidays.
- Necropsy of survivors performed: yes

Statistics:

No statistics were perfomed because it is not necessary

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

no mortality observed

Clinical signs:

other: Red feces;

Gross pathology:

no abnormalities detected

Interpretation of results:

GHS criteria not met

Conclusions:

Based on an acute oral toxicity study in rats, the oral LD50 of calcium 3-hydroxy-4-[(1-sulfonato-2-naphthyl)diazenyl]-2-naphthoate (CAS 6417-83-0) was found to exceed 5000 mg/kg bw/day.

Executive summary:

In an acute oral toxicity study male and female Sprague-Dawley Wiga rats were administered the test substance at a dose level of 5000 mg/kg bw (5 animals per sex per dose group) by oral gavage. CMC (carboxymethyl cellulose) was used as vehicle. Dosing was followed by a 15 day observation period. No deaths occurred and the clinical signs observed were red faeces. At autopsy no changes were seen. Therefore the LD50 of calcium 3-hydroxy-4-[(1-sulfonato-2-naphthyl)diazenyl]-2-naphthoate (CAS 6417-83-0) was considered to be > 5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

Both studies were performed before OECD and GLP guidelines were implemented. In spite of minor methodological restrictions and limited reporting, both studies are considered adequate for assessment (both Klimisch 2).

Acute toxicity: via inhalation route

Link to relevant study records

Reference

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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

September 2009

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Version / remarks:

August 1998

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

May 2008

Deviations:

no

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

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.

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

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).

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.

TEST ATMOSPHERE: see table 1

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The study was performed according to OECD/EC guidelines and GLP principles (Klimisch 1 study).

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In an acute oral toxicity study male and female Sprague-Dawley rats were administered the test substance at a dose level of 5000 mg/kg bw (5 animals per sex per dose group) by oral gavage. Polyethylene glycol/water (50:50) was used as vehicle. Dosing was followed by a 14 day observation period. No clinical symptoms were recorded and no deaths occurred. At autopsy no changes were seen. Therefore the LD50 of the test substance is > 5000 mg/kg bw.

In an acute oral toxicity study male and female Sprague-Dawley Wiga rats were administered the test substance at a dose level of 5000 mg/kg bw (5 animals per sex per dose group) by oral gavage. CMC (carboxymethyl cellulose) was used as vehicle. Dosing was followed by a 15 day observation period. No deaths occurred and the clinical signs observed were red faeces. At autopsy no changes were seen. Therefore the LD50 of the test substance is > 5000 mg/kg bw.

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 appr. 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

Justification for classification or non-classification

The available studies are considered reliable and suitable for classification purposes. Based on the available data, the substance is not classified for acute toxicity under Regulation (EC) No. 1272/2008.