Reaction product of Chloro[29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32]aluminium, sulphuric acid and caustic soda

Endpoint summary

Description of key information

The oral LD50 is 5581 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Groups of 5 male and 5 female rats, fasted overnight, were treated by single oral intubation. Physical condition and rate of deaths were monitored throughout the whole observation period of 14 days.

GLP compliance:

no

Remarks:

Study pre-dates GLP regulations

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

Name as used in the study report: FAT 60149/A.

Species:

rat

Strain:

other: Tif: RAIF (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST Animals
- Age at study initiation: 7 to 8 weeks old
- Mean body weights per group at study initiation: between 159 and 191 g.
- Fasting periode before study: overnight
- Housing: in groups of 5 in Macrolon cages (type 3)
- Diet: ad libitum rat food - NAFAG, Gossau SG
- Water: ad libitum
- Acclimation period: at least 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Photoperiod (hrs dark / hrs light): 14 / 10

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 or 20 mL/kg

Doses:

3000, 5000, 8000, 9000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: 1, 2, 4, 6, 24 hours after administration; daily from day 2 to day 14
- Frequency of weighing: immediately prior to dosing and at 7 and 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Statistics:

LD50 including 95 % confidence limits are calculated by the logit model.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

5 581 mg/kg bw

Based on:

test mat.

95% CL:

4 549 - 6 652

Remarks on result:

other: LD50 for male animals between 5000 and 8000 mg/kg bw and for female animals between 3000 and 5000 mg/kg bw.

Mortality:

- 3000 mg/kg bw: No mortality occurred.
- 5000 mg/kg bw: 0/5 male and 4/5 female animals died at day 1 of the test.
- 8000 mg/kg bw: 3/5 male and 5/5 female animals died at day 1 of the test.
- 9000 mg/kg bw: all animals died between day 1-2 of the test.

Clinical signs:

other: - 3000 mg/kg bw: sedation, dyspnoea, exophthalmos, ruffled fur, diarrhoea, curved body position (all slight). After 9 days no symptoms. - 5000 mg/kg bw: symptoms as described above; generally slight, some moderate sedation. After 9 days no symptoms. - 800

Gross pathology:

No substance related gross organ changes were seen.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

5 581 mg/kg bw

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Five rats per sex were exposed snout and nostrils only to an aerosol (dust: 1734 mg/m³) for 4 hours, followed by an observation period of 14 days. Inhalation toxicity was tested according to the method of Sachsse et al. (1973, 1976). K. Sachsse, L. Ullmann, G. Voss and R. Hess: Measurement of inhalation toxicity of aerosols in small laboratory animals. In: Proceedings of the Europ. Soc. for the Study of Drug Toxicity. Vol XV, pp. 236-251, Zurich, June 1973. K. Sachsse, L. Ullmann, K. Zbinden: Toxikologische Prufungen von Aerosolen im Tierexperiment: Aus "Chemische Rundschau" 29 (1976), Nr. 38 Seite 1-4.

GLP compliance:

no

Remarks:

Study pre-dates GLP regulations

Test type:

traditional method

Limit test:

no

Specific details on test material used for the study:

- Name of test substance as used in the study report: FAT 60149/B.

Species:

rat

Strain:

other: Tif: RAIf (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: young adult
- Weight at study initiation: Mean group weight males: 197-199 g; females 177-188g
- Housing: The males and females were segregated and kept in Macrolon cages, type 4, (10 animals to a cage)
- Diet: ad libitum rat food - NAFAG, Gossau SG, except during inhalation exposure
- Water: ad libitum, except during inhalation exposure
- Acclimation period: at least 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Photoperiod (hrs dark / hrs light): 14 / 10

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

clean air

Remark on MMAD/GSD:

The concentration and the particle size distribution of the aerosol in the vicinity of the animals were monitored at regular intervals throughout the aerosol exposure. The concentration was determined 5 times gravimetrically by sampling the test atmosphere through a selectron filter of 50 mm diameter and with a pore size of 0.2 µm (Schleicher and Schuell, Feldbach, Switzerland) at an air flow rate of 10 1/min. The size distribution of the particles was measured twice with a 4 stage Cascade Impactor with selectron filters of 25 mm diameter and with a pore size of 0.2 µm (Schleicher and Schuell) at an air flow rate of 17.5 L/min.
- Particle size distribution analysis of the chamber airborne particles showed that approximately 20 % were smaller than 7 µm in diameter.

Details on inhalation exposure:

For inhalation the rats were kept in separate PVC tubes positioned radially around the exposure chamber such that snout and nostrils of the animals only were exposed to the aerosol. During the exposure period the following parameters were controlled once at half time of the study inside the inhalation cylinder: temperature (with a Therm 2104 contact thermometer, Ahlborn Messund Regeltechnik, 815 Holzkirchen, Germany), relative humidity (with a VASALA Humidity Indicator HMI 11, Kelag AG, 8057 Zurich, Switzerland) and oxygen content (with a DRAEGER E 15 stationary control system, Draegerwerk AG, Liibeck, Germany) .
The aerosol was generated by injecting the solid test material with the help of a Grafix Exaktomat Injector (Cerutti AG, Bern, Switzerland) into an air stream which was discharged into the exposure chamber at a rate of 20 L/min.

CHAMBER CONDITIONS
- Temperature during the exposure period: 24 °C.
- Relative humidity during the exposure period: 64% for controls and 42% for exposed animals
- Oxygen content (Vol %): 21

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

1734 ± 181 mg/m3

No. of animals per sex per dose:

10

Control animals:

yes

Remarks:

10 males and 10 females exposed to clean air

Details on study design:

After 4 hour inhalation the rats were returned to their cages. Physical condition and incidence of death were monitored throughout an observation period of 14 days.

Statistics:

LC50 including 95 % confidence limits was calculated by the logit model.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 1 734 mg/m³ air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality occured at the tested concentration.

Clinical signs:

other: - Exposed: dyspnoea, exophthalmos (moderate), ruffled fur (moderate), ventral body position, curved body position. No symptoms after day 3. - Controls: no symptoms.

Body weight:

- Exposed: pre-test male/female 199/177 g, at day 7 male/female 239/200 g, at day 14 male/female 296/218 g.
- Controls: pre-test male/female 197/188 g, at day 7 male/female 236/213 g, at day 14 male/female 283/235 g.

Gross pathology:

No substance related gross organ changes were seen.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

1 700 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

An acute dermal toxicity study was conducted with the test substance on 5 male and 5 female rats with an exposure period of 24 hours and an observation period of 14 days.

GLP compliance:

no

Remarks:

Study pre-dates GLP regulations

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

- Test substance name as used in the study report: FAT 60149/B.

Species:

rat

Strain:

other: Tif: RAIf (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8 to 9 weeks
- Weight at study initiation: Mean group body weight Males 212-218 g; Females: 182-204 g
- Housing: Individually in Macrolon cages (type 2)
- Diet: ad libitum rat food - NAFAG, Gossau SG
- Water: ad libitum
- Acclimation period: at least 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Photoperiod (hrs dark / hrs light): 14 / 10

Type of coverage:

occlusive

Vehicle:

polyethylene glycol

Details on dermal exposure:

Approximately 24 hours before treatment an area on the back of the rats of approximately 60 square cm was shaved with an electric clipper. For treatment the test material was evenly dispersed on the skin with a syringe and was covered with an occlusive dressing which was fastened around the trunk with an adhesive elastic bandage. After 24 hours the dressing was removed, the skin was cleaned with lukewarm water and the reaction of the skin was appraised.

Duration of exposure:

24 hours

Doses:

2000, 2500, 3000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: 1, 2, 3, 5, 24 hours after administration, then daily
- Frequency of weighing: before administration, at 7 and 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: histopathology

Statistics:

LD50 including 95 % confidence limits are calculated by the logit model.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortallity occurred at the tested concentrations.

Clinical signs:

other: - Controls: no clinical symptoms - 2000 mg/kg bw: dyspnoea, exophthalmos, ruffled fur, curved body position. No symptoms after day 7. - 2500 mg/kg bw: same symptoms as above. - 3000 mg/kg bw: same symptoms as above.

Gross pathology:

At autopsy of treated and control rats no gross pathological changes were seen. At the site of the dermal treatment neither macroscopical nor histopathological findings which could be related to the dermal application of the substance were noted.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

3 000 mg/kg bw

Additional information

Acute oral toxicity

Several reliable acute oral toxicity studies, an acute inhalation toxicity study and two acute dermal toxicity studies are available and the methods and results are described below.

In the first study, groups of 5 male and 5 female rats, after having been fasted overnight, were given 3000, 5000, 8000 or 9000 mg/kg bw test stubstance suspended in polyethylene glycol by oral gavage (CIBA-GEIGY, 1979). Symptoms and mortality after administration were recorded during an observation period of 14 days. No mortality occurred at 3000 mg/kg bw. At 5000 mg/kg bw, no mortalities occurred in males, but 4/5 female animals died at day one of the test. At 8000 mg/kg bw, 3/5 male and 5/5 female animals died at day one of the test and at 9000 mg/kg bw, all animals died within 2 days. Clinical signs included sedation, dyspnoea, exophthalmos, ruffled fur, diarrhoea, curved body position and ventral body position. The surviving animals at all doses showed no symptoms after day 9. No dose-related differences in body-weight gain were observed. The LD50 was determined to be 5581 mg/kg bw (males and females together), with 95% CL of 4549-6652 mg/kg bw. For males, the LD50 was between 5000 and 8000 mg/kg bw and for females between 3000 and 5000 mg/kg bw.

In the second study (CIBA-GEIGY, 1980), groups of 5 male and 5 female mice, after being fasted overnight, were given 4000, 5000 or 6000 mg/kg bw, suspended in polyethylene glycol, by oral gavage. Symptoms and mortality after administration were recorded during an observation period of 14 days. No mortality occured at 4000 and 5000 mg/kg bw. At 6000 mg/kg bw 2/5 male and 2/5 female animals died within the first three days. Clinical signs included sedation, dyspnoea, ruffled fur, diarrhoea and curved body position. The surviving animals showed no symptoms after day 7. No dose-related differences in body-weight gain were observed. Based on the results, the test substance was reported to have an LD50 of approximately 6000 mg/kg bw (for both males and females).

In the third study, groups of 5 male and 5 female Chinese hamsters, after being fasted overnight, were given 2000, 3000, 4000 or 5000 mg/kg bw of the test substance, suspended in polyethylene glycol, by oral gavage (CIBA-GEIGY, 1980). Symptoms and mortality after administration were recorded during an observation period of 14 days. No mortality occurred at any of the doses. Clinical signs observed included sedation, dyspnoea, ruffled fur and curved body position. No symptoms were observed after day 6 and no dose-related differences in body weight gain were observed. Based on the test results, the test substance has an LD50 > 6000 mg/kg bw in Chinese hamsters.

Acute inhalation toxicity

An acute inhalation study was done with a single dose of 1734 ± 181 mg/m3 in the form of dust in 10 male and 10 female rats, with a control group of 10 male and 10 female rats that were administered filtered air (CIBA-GEIGY, 1980). Particle size distribution analysis of the chamber airborne particles showed that approximately 20 % were smaller than 7 µm in diameter. Symptoms and mortality after administration were recorded during an observation period of 14 days. No mortality occurred in this study. Clinical symptoms observed were dyspnoea, exophthalmos, ruffled fur, ventral body position and curved body position. No symptoms were observed after day 3. There was no different change in body weight between treated and control animals. The LD50 was determined to be >1700 mg/m3

Acute dermal toxicity

The first acute dermal study was done with groups of 5 male and 5 female rats, that were given 0 (controls), 2000, 2500 or 3000 mg/kg bw test substance, suspended in polyethylene glycol, dispersed on 60 square cm on the shaved back of the animals (CIBA-GEIGY, 1980). It is reported that higher doses could not be administered, but no further explanation is provided. After administration, the test material was covered with an occlusive dressing. After 24 hours, the dressing was removed, the skin was cleaned with lukewarm water and the reaction of the skin was appraised. Mortalilty and clinical symptoms were observed during 14 days after administration. In this study, no mortality was observed. Clinical symptoms that were observed included dyspnoea, exphthalmos, ruffled fur and curved body position. All animals were recovered after 7 days, based on lack of symptoms from that day. No dose-dependent changes in body weight gain were observed. The LD50 exceeded 3000 mg/kg bw.

An second acute dermal study was done with groups of 3 male and 3 female rabbits, that were given 0 (controls), 2000 or 6000 mg/kg bw on the shaved back (CIBA-GEIGY, 1980). The test substance was suspended in polyethylene glycol, dispersed on the skin and covered with an occlusive dressing. After 24 hours the dressing was removed and the skin was cleaned with lukewarm water. The reaction of the skin was appraised according to Draize. Mortality and symptoms were observed for 14 days. No mortality occurred in this study. Clinical signs were sedation and ruffled fur in the first 8 days. No skin irritation or necrosis was observed at any point during the study. No dose-dependent differences in body weight gain were observed. Based on the test results, the substance has a dermal LD50 of > 6000 mg/kg bw in rabbits.

Other

In two intravenous studies (mice and rats) and one intraperitoneal study (mice), LD50 values between > 100 mg/kg bw, but < 300 mg/kg bw (intravenous mouse), 828 mg/kg bw (intravenous rat), and 540 mg/kg bw (intraperitoneal) were determined. The LD50 values with these administration routes are clearly lower than with oral, inhalation or dermal administration. This may be explained by the effect of lower absorption via these routes and/or effects of metabolism occurring via these routes. The observed symptoms were similar to those in the other studies.

Conclusion

The LD50 values obtained in the reliable oral studies range from 5581 to >6000 mg/kg bw. In the inhalation study, with only a single dose and a control group, no mortality occurred and the LC50 was determined to exceed 1.7 mg/L. The two dermal studies, also showed no mortality up to 6000 mg/kg bw in rabbits and up to the highest dose that could be administered in rats (3000 mg/kg bw).

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. For all routes of exposure, the test substance does not fulfil the criteria for classification for acute toxicity under Regulation (EC) No. 1272/2008.