[2,9,16,23-tetrachloro-29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32]copper

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Well documented study; however the tested material was a mixture and is therefore not equivalent to submission substance identity.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Imron paint & Desmodur N-100 (mixture of various compounds, including CAS No 1328-53-6 in unspecified quantity)

IUPAC Name:

Imron paint & Desmodur N-100 (mixture of various compounds, including CAS No 1328-53-6 in unspecified quantity)

Details on test material:

- Name of test material (as cited in study report): Mixture (Imron Paint Formulated with and without Desmodur N-100)
- Analytical purity and composition: no data given

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, New York
- Age at study initiation: 8 weeks
- Weight at study initiation: 207 - 253 g
- Housing: 2 animals per cage
- Diet: Purina Certified Rodent Chow (R) #5002, ad libitum, except during exposure
- Water: ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature: 20-25 °C
- Humidity: 36-60 %
- Photoperiod: 12 hrs dark / 12 hrs light

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

A gravimetric analyses was used to monitor total particulate. A gas chromatographic method and a liquid chromatographic method were also used to quantify specific ingredients of the mixture.

Duration of treatment / exposure:

2 weeks

Frequency of treatment:

6 hours/day, 5 days/week

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 0.01, 0.03, 0.1 mg/l (0, 9.7, 30, 96 mg/m3)
Basis:
nominal conc.

No. of animals per sex per dose:

10 animals per dose.

Control animals:

other: air only

Details on study design:

Test animals (10 per exposure group) were exposed to Imron Paint Formulated with Desmodur N-100 or clean air (control group). One additional group of 10 rats was exposed to Imron Paint Formulated without Desmodur N-100.
5 rats were sacrificed after the 10th exposure, and the remaining 5 rats were sacrificed on day 14 of the recovery for gross and histopathology examinations.
Post-exposure period: 5 rats/group were killed immediately and 5 rats/group were allowed to recover for 14 days post exposure

Examinations

Observations and examinations performed and frequency:

Mean body weights ofthe rats of the test group were compared to controls during exposure and recovery period.
Blood and urine samples were collected for clinical analysis.

Sacrifice and pathology:

At the end of the exposure period 5 rats per group were killed for pathologic examination. Remaining rats were observed tor 14 days post exposure, and were given the same clinical and pathological examinations.
Organs and tissues were collected for pathology (heart, lungs, nasalcavities, mesenteric lymph node, trachea, liver, pancreas, esophagus, stomach, intestine, kidneys, urinary bladder, bone marrow, spleen, thymus, thyroid, testes, epididymides, adrenal glands, brain and eyes).

Results and discussion

Results of examinations

Details on results:

No differences to the control were observed in mean body weights for exposed rats throughout the study. Rats in all exposure groups were stained green by the test materials after exposures. In addition, rats exposed to 0.03 or 0.1 mg/l of test mixture with or 0.1 mg/l test mixture without Desmodur N-100 had lung noise after each exposure.

Clinical chemical analyses after 10 exposures revealed decreased serum alkaline phosphatase activities in rats exposed to 0.1 mg/l test mixture with or without Desmodur N-100. This change was absent after 14 days recovery. No other adverse clinical chemical or hematologic changes were observed in any group.

Pathologic examination revealed dose-dependent accumulations of paint-containing alveolar macrophages in the lungs of all exposed rats both after 10 exposures and after 14 days recovery. In addition, at concentrations greater 0.1 mg/l, the mediastinal lymph nodes and/or lungs were stained green. No significant inflammatory lesions were observed in the lungs of rats exposed to test mixture containing Desmodur N-100 at any exposure concentration. In contrast, rats exposed to 0.1 mg/l of test mixture without Desmodur N-100 had elevated lung weights and multiple foci of subacute inflammation in the lungs at both sacrifices, and granulomatous inflammation in the mediastinal lymph nodes after 14 days recovery.

No significant adverse effects were observed in rats exposed to 0.1 mg/l of test mixture containing Desmodur N-100. The 0.1 mg/l level is considered a no-effect concentration under the conditions of this test. Test mixture without Desmodur N-100 caused more severe effects than with Desmodur N-100.

Effect levels

Dose descriptor:

NOAEL

Effect level:

9.7 mg/m³ air (nominal)

Sex:

male

Target system / organ toxicity

Critical effects observed:

not specified