Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Toxicity to reproduction

Currently viewing:

Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1995
Report date:
1995
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 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

Constituent 1
Chemical structure
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
Test material form:
solid
Specific details on test material used for the study:
- Name of test material (as cited in study report): Phthalocyanine Blue
- Analytical purity: 99.55 %
- Storage condition of test material: room temperature
- Structural formula attached as image file (if other than submission substance): see Fig.

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 / concentrationsopen allclose all
Dose / conc.:
40 mg/kg bw/day (nominal)
Remarks:
The applied volume was 10 ml/kg bw/day for each dose; the respective concentrations of the test substance was 0.4 % (w/v).
Dose / conc.:
200 mg/kg bw/day (nominal)
Remarks:
The applied volume was 10 ml/kg bw/day for each dose; the respective concentrations of the test substance was 2 % (w/v).
Dose / conc.:
1 000 mg/kg bw/day (nominal)
Remarks:
The applied volume was 10 ml/kg bw/day for each dose; the respective concentrations of the test substance was 10 % (w/v).
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)

General toxicity (P0)

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
A blue coloration of faeces was noted in all animals of the groups receiving 40 mg/kg bw/day or more. These changes were due to the colour of the test substance
Mortality:
no mortality observed
Description (incidence):
No changes were observed in terms of mortality.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No changes were observed in terms of body weight.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
No changes were observed in terms of food consumption.
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
No changes were observed in terms histopathological examination.

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
no effects observed
Reproductive performance:
no effects observed
Description (incidence and severity):
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
Sex:
male/female
Basis for effect level:
other: No treatment-related adverse effects observed up to the highest tested dose.

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Description (incidence and severity):
No findings were recorded with regard to general condition.
Mortality / viability:
no mortality observed
Description (incidence and severity):
No findings were recorded with regard to survivability. The number of living and dead pups was not affected.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No findings were recorded with regard to body weights.
Sexual maturation:
no effects observed
Description (incidence and severity):
The sex of the pubs was not affected.
Gross pathological findings:
no effects observed
Description (incidence and severity):
No findings were recorded with regard to autopsy (visual observation) of the pups. The external appearance were also not affected.

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
1 000 mg/kg bw/day
Sex:
male/female
Basis for effect level:
other: No treatment-related adverse effects observed up to the highest tested dose.

Overall reproductive toxicity

Reproductive effects observed:
no

Any other information on results incl. tables

The estimated NOAELs in this study were 1000 mg/kg bw/day for both the parental generation and for the F1 generation. Although premating exposure was relatively short for male animals in this screening test, the subchronic NOAEL of 200 mg/kg bw/day, also see in chapter 7.5 Repeated Dose Toxicity) was less than the fertility NOAEL of 1000 mg/kg bw/day herein. The test substance could therefore be considered as non toxic to fertility under the test conditions chosen, since actual exposure levels will clearly be less than the dose related to the NOAEL obtainedin the present study.

Applicant's summary and conclusion