2,9,16,23-tetrakis(2,5-di-tert-butyl-4-methoxyphenoxy)phthalocyanine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27th February 2019 - 11th April 2019

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

EC No 440/2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF Guidelines

Version / remarks:

2000, including the most recent versions.

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,9,16,23-tetrakis(2,5-di-tert-butyl-4-methoxyphenoxy)phthalocyanine

EC Number:

831-167-5

Cas Number:

2126827-44-7

Molecular formula:

C92H106N8O8

IUPAC Name:

2,9,16,23-tetrakis(2,5-di-tert-butyl-4-methoxyphenoxy)phthalocyanine

Test material form:

solid

Specific details on test material used for the study:

Batch (Lot) Number: 2715/18/01
Expiry date: 01 July 2020 (expiry date)
Physical Description: Dark green solid
Purity/Composition: 99%
Storage Conditions: At room temperature protected from light
Test item handling: Use amber glassware or wrap container in aluminum foil

Test animals

Species:

rat

Strain:

other: Wistar Han

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: Young adult animals (approximately 9-10 weeks old)
- Weight at study initiation: 161 to 187 g
- Fasting period before study: Overnight (a maximum of 20 hours) prior to dosing and until 3-4 hours after administration fo the test item. Water was available.
- Housing: Polycarbonate cages (Makrolon MIV, 18cm height). Maximum of 3 animals (same sex and dose group) per cage.
- Diet: Pelleted rodent diet (SM R/M-Z), ad libitum
- Water: Municipal tap-water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Target - 18 to 24 °C; Actual daily mean - 21 °C
- Humidity (%): Target - 40 to 70%; Actual daily mean – 38 to 52%
Note: the humidity levels were outside of the target range occasionally for 3 days with a minimum of 38%. No noticeable effects on the clinical condition of the animals were observed.
- Air changes (per hr): 10 or more changes per hour with 100% fresh air.
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light

IN-LIFE DATES:
From: 27th February, 2019 (experimental start date)
To: 11th April, 2019

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Remarks:

Specific gravity: 0.92

Details on oral exposure:

Single oral dose VEHICLE
- Concentration in vehicle: 100% - corn oil used neat.
- Amount of vehicle (if gavage): Appropriate volumes to give a dose volume of 10 mL/kg body weight
- Justification for choice of vehicle: Trial prepatations were undertaken to select the suitable vehicle and to establish a suitable formulation procedure.
- Purity: 100%

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight

Doses:

300 and 2000 mg/kg body weight

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Day 1 (predose), Day 8, and Day 15
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, body weights, macroscopic examination

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

300 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Remarks:

At 300 mg/kg, hunched posture was noted for all animals on Day 1. Green discolouration of the faeces was noted in all animals between Days 2 and 5, which was considered to be caused by the staining properties of the substance. No mortality occurred.

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Remarks:

Hunched posture and/or piloerection were noted for the animals on Days 1 and/or 2. Green discolouration of the faces was noted in all animals between Days 2 and 5, which was considered to be caused by the staining properties of the substance.No mortality occurred.

Mortality:

All (6/6 females) animals survived the limit dose of 2000 mg/kg body weight.

Clinical signs:

other: At 300 mg/kg, hunched posture was noted for all animals on Day 1. At 2000 mg/kg, hunched posture and/or piloerection were noted for the animals on Days 1 and/or 2. Green discolouration of the faces was noted in all animals between Days 2 and 5, which was

Gross pathology:

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

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 in an acute toxicity study conducted on the substance in female rats administered via gavage is >2000 mg/kg bw.

Executive summary:

In a reliable in vivo acute oral toxicity study conducted in accordance to OECD guideline 423, the substance was administered to female Wistar Han rats in a single dose by oral gavage at 300 (3 animals) and 2000 (6 animals) mg/kg body weight. All (6/6 females) animals survived in the highest dose group of 2000 mg/kg body weight. The substance did not cause death or evident signs of toxicity. During the observation period of 15 days, no other signs of intoxication, change of health, nor any other adverse reactions were seen. Macroscopic examination of the animals at the end of the study did not reveal treatment-related changes. The LD50 of the substance is considered to be greater than 2000 mg/kg body weight after single oral administration to female Wistar Han rats.