Copper, [29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32]-, [[3-(1-methylethoxy)propyl]amino]sulfonyl derivs.

Endpoint summary

Description of key information

The substance is virtually nontoxic after a single administration as an aqueous suspension as rats survived application of 10000 mg/kg bw without showing signs of intoxication (Ciba-Geigy Ltd. 1972). Dosing of hamsters with an excessive solution in oil resulted in mortality at 3000, but not at 1000 mg/kg bw (Ciba-Geigy Ltd. 1982).

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable study report which meets basic scientific principles (TS purity not provided, 8-day observation period, no GLP).

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

8-day observation period

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: CFE (RAC, SPF) strain

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Weight at study initiation: 126 - 143 g (mean: 135 - 136 g)
- Housing: groups of 5 animals in macrolon cages (size 3)
- Diet (ad libitum): Standard diet of Nafag; ad libitum
- Water (ad libitum): drinking water; ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1 °C
- Humidity (%): 55 ± 5 %
- Photoperiod (hrs dark / hrs light): 14 hours light/day; 10 hours dark/day

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

0.5% CMC in tap water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25 and 50% respectively for the low and high dose groups

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg bw

Doses:

5000 and 10000 mg/kg bw

No. of animals per sex per dose:

5000 mg/kg bw: 5 male and 5 female animals
10000 mg/kg bw: 3 male and 2 female animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 8 days
- Necropsy of survivors performed: no data
- Other examinations performed: clinical signs, body weight

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality occurred up to this dose level

Mortality:

No mortality.

Clinical signs:

other: None observed. Black stained feces were observed in both dose groups.

Gross pathology:

No data.

Table 1: Body weights

Dose level (mg/kg bw)	Mean body weights (g)
	Pre-test	On day 8 of test
5000	135	194
10000	136	195

 

Interpretation of results:

practically nontoxic

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

10 000 mg/kg bw

Quality of whole database:

valid

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In order to determine the dose/response relationship following the administration of single oral doses of the test material, groups of 3-5 male and 2-5 female rats received by gavage doses of 5000 or 10000 mg/kg bw suspended with 0.5% carboxymethylcellulose and tap water. The total volume given was 20 ml/kg body weight.

Symptoms and mortality after administration were recorded during an observation period of 8 days. Animals excreted black feces. No mortality and no effects on body weight were observed.

The study is valid with restrictions as it was performed prior to the introduction of GLP and had an observation period of 8 instead of 14 days. It should be noted that in the study with hamsters, mortality occurred within the first three days, so the chance of missing a delayed toxicity is low. Considering the excessive doses and the absence of findings, this study is acceptable for the purpose of classification and labeling.

 

A second study is available in Chinese Hamster. In contrast to the study in rats, peanut oil was used as vehicle. The study followed OECD guideline 401 but was not performed according to GLP. It is described in detail and allows reliable interpretation of the data.

Both males and females were tested and there was no specific sensitivity of one gender. Only unspecific symptoms (dyspnea, exophthalmus, ruffled fur, curved body position) were seen at the dose levels of 300, 1000, 3000 mg/kg bw. The applied volume was 10 or 20 ml per kg bw which exceeds standard requirements for rodents and is excessive particularly for oil as a vehicle. No compound related gross organ changes were observed upon necropsy Mortality occurred only at the dose group of 3000 mg/kg bw and it involved all animals. Death occurred within 5 hours for males and within 5h to three days for females.

 

The substance is highly soluble in octanol and it is expected that it is well soluble in peanut oil. This may result in a different systemic uptake after ingestion and explain the lower oral toxicity using aqueous carboxymethylcellulose as vehicle.

According to the guidelines, an aqueous vehicle should be considered first. Only as a second choice, oil may be used, but its volume must not exceed 10 ml/kg bw. This has been exceeded in this study and it is possible that this has contributed to the toxicity of the substance.

 

Overall, the study in rats is chosen as the key study for classification and labeling.

Justification for selection of acute toxicity – oral endpoint
Adequate study and relevant species for classification and labelling.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for acute oral toxicity under Directive 67/548/EEC, as amended for the 28th time in Directive 2001/59/EC.

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008.

A s a result the substance is not considered to be classified for acute oral toxicity under Regulation (EC) No. 1272/2008, as amended for the fifth time in Directive EC 944/2013.