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

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Peer reviewed GLP guideline study.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

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:

other: 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

IUPAC Name:

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

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)

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

Analytical verification of doses or concentrations:

not specified

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.

Duration of treatment / exposure:

Administration period (males): from 14 days before mating, during the mating period and copulation, until 46 days
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.

Duration of test:

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

Doses / concentrations

Remarks:

Doses / Concentrations:
40, 200, 1000 mg/kg bw/day
Basis:
nominal conc.
The applied volume was 10 ml/kg bw for each dose; the respective concentrations of the test substance were 0, 0.4, 2 and 10 % (w/v).

No. of animals per sex per dose:

12 animals per sex per dose

Control animals:

yes, concurrent vehicle

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: at least once every day visual inspection, observation of appearance and palpation
DETAILED CLINICAL OBSERVATIONS: reproductive capacity, examination of the oestrous cycle, 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

Ovaries and uterine content:

The ovaries and uterine content were examined after termination
The examinations included:
- Gravid uterus weight
- Number of corpora lutea
- Number of implantations

Fetal examinations:

- General observations about the state (clinical signs, body weight change) and neonatal survival status
- Post-mortem: The whole body was fixed in formalin solution

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Details on maternal toxic effects:
PARENTAL TOXICITY:
A blue coloration of faeces was noted in all animals of the groups receiving 40 mg/kg bw 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 group and in almost all animals of both sexes in the 1000 mg/kg 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 (maternal animals)

1

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day

Basis for effect level:

other: maternal toxicity

2

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
No significant differences were observed in rate of live/dead pups born: In the control group, 1 out of 69 male and 3 out of 75 female pups were born dead. In the 40 mg/kg bw/day group, 4 out of 60 males and 2 out of 48 females as well as 1 pup of unknown sex were born dead. In the 200 mg/kg bw/day group, 3 out of 75 male and 2 out of 78 female pups were born dead. In the 1000 mg/kg bw/day group, 3 out of 64 male and 5 out of 69 female pups were born dead.
No evidence was found suggesting a relation with the administration of the tested substance and clinical signs, body weight change or autopsy findings for both male and female pups.

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified