Copper, [29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32]-, (1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)methyl derivs.

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

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

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

1995

Report date:

1995

Reference 2

Reference Type:

publication

Title:

Preliminary Reproduction Toxicity Screening Test of Phthalocyanine Blue in Rats

Author:

Japan Existing Chemical Data Base (JECDB)

Year:

2009

Bibliographic source:

http://dra4.nihs.go.jp/mhlw_data/home/file/file147-14-8.html (original report is in Japanese; the web site was translated to English using the Google language tool http://www.google.de/language_tools?hl=de)

Reference 3

Reference Type:

secondary source

Title:

Final SIDS Initial Assessment Profile on C.I. Pigment Green 7 Copper, [tetradecachloro-29H, 31 H-phthalocyaninato(2-)-N{29},N{30},N{31},N{32}]

Author:

OECD

Year:

2005

Bibliographic source:

SIDS

Report date:

2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32 copper

EC Number:

205-685-1

EC Name:

29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32 copper

Cas Number:

147-14-8

Molecular formula:

C32H16CuN8

IUPAC Name:

[29H,31H-phthalocyaninato(2-)-kappa~2~N~29~,N~31~]copper

Constituent 2

Reference substance name:

copper phthalocyanine

IUPAC Name:

copper phthalocyanine

Test material form:

solid

Details on test material:

- Name of test material (as cited in study report): Phthalocyanine Blue
- Analytical purity: 99.55 %
- Storage condition of test material: room temperature

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Japan
- Age at study initiation: 8 weeks
- Weight at study initiation: females: ca. 232 g; males: ca. 372 g
- Housing: bracket type metal wire mesh floor cages (260 x 380 x 180 mm)
- Diet: Feed-solid diet (CRF-1, Oriental Yeast Co, Ltd., Inc.), ad libitum)
- Water: tap water, ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature: 23 +- 3 °C
- Humidity: 55 +- 10 %
- Air changes: 10-15 times per hr
- Photoperiod: 12 hrs dark / 12 hrs light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on exposure:

The test substance was dosed orally to male rats for 46 days included before mating and mating period, and to female rats from day 14 before mating to day 3 of lactation.

The test substance was administered into the stomach by gavage.
10 ml per kg body weight was calculated based on the weight

Details on mating procedure:

According to OECD Guideline 421, 1:1 (one male to one female) matings were used. The female was placed with the same male until pregnancy occured or two weeks had elapsed. Each morning the females were examined for the presence of sperm or a vaginal plug. Day 0 of pregnancy was defined as the day a vaginal plug or sperm was found.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Administration period (males): from 14 days before mating, the mating period until copulation, and also 46 days after the start of copulation
Administration period (females): from 14 days before mating to day 3 of lactation
Duration of test: Males were killed on days 28 and 47, females on day 28 and on day 4 of lactation

Frequency of treatment:

daily; administration time was between 10 h and 13 h.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

40 mg/kg bw/day (actual dose received)

Doses / concentrations 2

Dose / conc.:

200 mg/kg bw/day (actual dose received)

Doses / concentrations 3

Dose / conc.:

1 000 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

12 animals per sex per dose

Control animals:

yes, concurrent vehicle

Details on study design:

Parental males were killed on days 28 and 47, parental females on day 28 and on day 4 of lactation

Examinations

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: at least once every day visual inspection, observation of appearance and palpation
DETAILED CLINICAL OBSERVATIONS: reproductive capacity, the recording of occurrence of copulation and gestation, fertility, implantation, delivery and nursing indices, maternal behaviour, birth rate, pregnancy period
BODY WEIGHT: examination of body weight was conducted
FOOD CONSUMPTION: examination of feed intake was conducted
POST-MORTEM EXAMINATIONS: Organs were removed, reproductive organs were weighed
HISTOPATHOLOGICAL EXAMINATION: Ovaries, uterus, harderian gland, eyeball, mammary gland, spleen

Oestrous cyclicity (parental animals):

examination of the oestrous cycle was conducted

Litter observations:

The following parameters were examined in F1 offspring:
number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, physical or behavioural abnormalities,

Postmortem examinations (parental animals):

POST-MORTEM EXAMINATIONS: Organs were removed, reproductive organs were weighed
HISTOPATHOLOGICAL EXAMINATION: Ovaries, uterus, harderian gland, eyeball, mammary gland, spleen, testes, epididymis (left and right)

Postmortem examinations (offspring):

Post-mortem: The whole body was fixed in formalin solution

Results and discussion

Results: P0 (first parental generation)

Details on results (P0)

PARENTAL TOXICITY:
A blue coloration of faeces was noted in all animals of the groups receiving 40 mg/kg bw/day or more; moreover blue-green or grayish blue discolorations of the contents of the stomach and intestines were noted in a few animals of the 200 mg/kg bw/day group and in almost all animals of both sexes in the 1000 mg/kg bw/day group. These changes were due to the colour of the test substance. No changes were observed in terms of mortality, body weight, food consumption, organ weight and histopathological examination.

TOXICITY TO FERTILITY:
No effects were noted on the following endpoints: Reproductive ability of either sex (assessment of this endpoint included the examination of the oestrous cycle, the recording of occurrence of copulation and gestation, the calculation of copulation, fertility, implantation, delivery and nursing indices, the weight of testes and epididymis as well as histopathological examination of the reproductive organs), delivery, maternal behavior, viability, clinical signs and body weight changes.

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: absence of effects

Target system / organ toxicity (P0)

Critical effects observed:

no

Results: P1 (second parental generation)

Effect levels (P1)

Dose descriptor:

NOEL

Effect level:

1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: absence of effects

Target system / organ toxicity (P1)

Critical effects observed:

no

Results: F1 generation

Details on results (F1)

FETOTOXICITY:
No findings were recorded with regard to general condition, survivability, body weights and autopsy (visual observation) of the pups. The number of living and dead pups as well as their sex and external appearance were also not affected.

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

1 000 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: absence of effects

Target system / organ toxicity (F1)

Critical effects observed:

no

Results: F2 generation

Effect levels (F2)

Remarks on result:

not measured/tested

Overall reproductive toxicity

Reproductive effects observed:

no