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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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from J-check

Data source

Reference
Reference Type:
other:
Title:
Combined Repeated Dose Toxicity Study with the Reproduction/ Developmental Toxicity Screening Test (OECD TG422) of Pigment Orange 13 in rats
Author:
J-CHECK
Year:
2010
Bibliographic source:
Hazard-Data Evaluation Committee of National Institute of Technology and Evaluation based on the GLP study report obtained by Japanese Ministry of Economy, Trade and Industry. Ministry of Economy, Trade and Industry, Japan, 2010

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
Principles of method if other than guideline:
Combined Repeated Dose Toxicity Study with the Reproduction/ Developmental Toxicity Screening Test (OECD TG422) of Pigment Orange 13 in rats
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
4,4'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one]
EC Number:
222-530-3
EC Name:
4,4'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one]
Cas Number:
3520-72-7
Molecular formula:
C32H24Cl2N8O2
IUPAC Name:
4,4'-(1E,1'E)-(3,3'-dichlorobiphenyl-4,4'-diyl)bis(diazene-2,1-diyl)bis(3-methyl-1-phenyl-1H-pyrazol-5(4H)-one)
Details on test material:
- Name of test material (as cited in study report): Pigment Orange 13
- Molecular formula (if other than submission substance): C32H24Cl2N8O2
- Molecular weight (if other than submission substance): 623.5016 g/mole
- Substance type: Organic
- Physical state: Orange powder
Specific details on test material used for the study:
- Name of test material (as cited in study report): Pigment Orange 13
- Molecular formula (if other than submission substance): C32H24Cl2N8O2
- Molecular weight (if other than submission substance): 623.5016 g/mole
- Substance type: Organic
- Physical state: Orange powder
- Impurities (identity and concentrations): < 1%

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Age at study initiation: (P) x wks; (F1) x wks: 9 weeks old

Administration / exposure

Route of administration:
oral: gavage
Type of inhalation exposure (if applicable):
not specified
Vehicle:
water
Details on exposure:
Not specified
Details on mating procedure:
Not specified
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
Not specified
Duration of treatment / exposure:
- Male: 42 days
- Female: 41 - 47 days (from 14 days before mating to day 4 of lactation)
Frequency of treatment:
Daily
Details on study schedule:
Not specified
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day
Dose / conc.:
40 mg/kg bw/day
Dose / conc.:
200 mg/kg bw/day
Dose / conc.:
1 000 mg/kg bw/day
No. of animals per sex per dose:
Total: 116
For male
0 mg/kg/day: 12 male, 12 female
40 mg/kg/day: 12 male, 12 female
200 mg/kg/day: 12 male, 12 female
1000 mg/kg/day: 12 male, 12 female

Recovery
0 mg/kg/day: 5 male, 5 female
1000 mg/kg/day: 5 male, 5 female
Control animals:
yes, concurrent vehicle
Details on study design:
Not specified
Positive control:
Not specified

Examinations

Parental animals: Observations and examinations:
Survival, Clinical sign, Body weight and weight gain, food consumption, urinalysis, Hematology and clinical chemistry were examined.
Oestrous cyclicity (parental animals):
Estrous cycle was examined.
Sperm parameters (parental animals):
Not specified
Litter observations:
Mortality, Sex ratio or body weight on day 0 and 4 of lactation, or viability
Postmortem examinations (parental animals):
Organ weight, Gross pathology and histopathology was examined.
Postmortem examinations (offspring):
External and macroscopic abnormalities were examined.
Statistics:
Not specified
Reproductive indices:
Copulation index, fertility index, or pairing days until copulation, delivery index, birth index, live birth index and viability index were observed.
Offspring viability indices:
viability index on day 0 and 4

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Description (incidence and severity):
No clinical sign were observed during the study in treated rats.
Dermal irritation (if dermal study):
not specified
Mortality:
no mortality observed
Description (incidence):
No mortality were observed in treated male and female rats as compared to control.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No significant effect on body weight gain of male and female rats was observed as compared to control.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
No effect on food consumption of treated male and female rat was observed as compared to control.
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Description (incidence and severity):
No effect on hematology of treated male and female rat was observed as compared to control.
Clinical biochemistry findings:
no effects observed
Description (incidence and severity):
No effect on Clinical chemistry of treated male and female rat was observed as compared to control.
Urinalysis findings:
no effects observed
Description (incidence and severity):
No changes in urinalysis were observed in treated rats as compared to control.
Behaviour (functional findings):
no effects observed
Description (incidence and severity):
No changes in reflex/reaction, grip strength, or locomotor activity were observed in treated male and femlae rats as compared to control.
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
No effect on organ weight of treated male and female rat was observed as compared to control.
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
no effects observed
Description (incidence and severity):
No effect on estrous cycle, number of corpora lutea or implantations was observed in treated rats as compared to control.
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed
Description (incidence and severity):
No effect on Copulation index, fertility index, or pairing days until copulation, delivery index was observed in treated rats as compared to control.

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:
clinical signs
mortality
body weight and weight gain
food consumption and compound intake
haematology
clinical biochemistry
urinalysis
organ weights and organ / body weight ratios
histopathology: non-neoplastic
reproductive function (oestrous cycle)
reproductive performance
Remarks on result:
other: No effect observed

Target system / organ toxicity (P0)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
no mortality observed
Description (incidence and severity):
No effect on viability of pups were observed on day 0 and 4 as compared to control.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No effect on body weight of pups were observed on day 0 and 4 as compared to control.
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
no effects observed
Description (incidence and severity):
No external abnormality were observed in pups as compared to control.
Histopathological findings:
no effects observed
Description (incidence and severity):
No histopathological abnormality were observed in pups as compared to control.
Other effects:
no effects observed

Developmental neurotoxicity (F1)

Behaviour (functional findings):
no effects observed

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
no effects observed

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:
viability
mortality
body weight and weight gain
gross pathology
histopathology: non-neoplastic
Remarks on result:
other: No effect obseved

Target system / organ toxicity (F1)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Overall reproductive toxicity

Reproductive effects observed:
not specified
Treatment related:
not specified
Relation to other toxic effects:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Applicant's summary and conclusion

Conclusions:
NOAEL was considered to be 1000 mg/kg bw for P and F1 generation when Crl:CD(SD) male and female rats were treated with Pigment Orange 13 orally by gavage for 47 days.
Executive summary:

In a Combined Repeated Dose Toxicity Study with the Reproduction/ Developmental Toxicity Screening Test,Crl:CD(SD) male and female rats were treated with Pigment Orange 13 in the concentration of0, 40, 200, 1000 mg/kg bw/day orally by gavage for 41 - 47 days (from 14 days before mating to day 4 of lactation. No mortality, Clinical signs,   behavior modification,change in Body weight and Food consumption of treated rats were observed as compared to control. Similarly, No significant effect on Urinalysis, Hematology, Blood chemistry, Organ weight and Histopathology of treated rat were observed as compared to control rats. In addition, no effect on reproductive parameters of treated rats were observed such as estrous cycle, number of corpora lutea or implantations, Copulation index, fertility index, or pairing days until copulation and delivery index of treated rat as compared to control.No effect on organ weight and histopathological changes were observed in treated male and female rats as compared to control.No effect on viability of pups and body weight were observed on day 0 and 4 as compared to control. No external and histopathological abnormality and were observed in pups as compared to control. Therefore, NOAEL was considered to be 1000 mg/kg bw for P and F1 generation when Crl:CD(SD) male and female rats were treated with Pigment Orange 13 orally by gavage for 47 days.