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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
multi-generation reproductive 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 from secondary source

Data source

Reference
Reference Type:
secondary source
Title:
Toxicological Evaluation of certain food additives
Author:
The Joint FAO/WHO Expert Committee on Food Additives (JECFA)
Year:
1981
Bibliographic source:
The Joint FAO/WHO Expert Committee on Food Additives (JECFA)

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
other: As mentioned below
Principles of method if other than guideline:
Multigeneration toxicity study of test material was performed on male and female wistar rats.
GLP compliance:
not specified
Limit test:
no
Justification for study design:
No data available

Test material

Constituent 1
Chemical structure
Reference substance name:
Tetrasodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate
EC Number:
219-746-5
EC Name:
Tetrasodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate
Cas Number:
2519-30-4
Molecular formula:
C28H21N5O14S4.4Na
IUPAC Name:
tetrasodium 4-acetamido-5-hydroxy-6-({7-sulfonato-4-[(4-sulfonatophenyl)diazenyl]-1-naphthyl}diazenyl)naphthalene-1,7-disulfonate
Details on test material:
IUPAC Name: Tetrasodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonateCommon Name: C.I. Food Black 1, Brilliant Black 1Molecular Formula:C28H21N5O14S4.4NaMolecular Weight: 867.6873 g/molSubstance Type: OrganicPhysical state: Solid
Specific details on test material used for the study:
No data available

Test animals

Species:
rat
Strain:
Wistar
Details on species / strain selection:
No data available
Sex:
male/female
Details on test animals or test system and environmental conditions:
No data available

Administration / exposure

Route of administration:
oral: feed
Vehicle:
not specified
Details on exposure:
No data available
Details on mating procedure:
No data available
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
From F1 to F3 generation
Frequency of treatment:
No data available
Details on study schedule:
No data available
Doses / concentrations
Remarks:
0, 0.1, 1.0 or 3% (0, 50, 500,1500 mg/kg bw per day)
No. of animals per sex per dose:
Total:3600 mg/kg bw: 60 male and 60 female 50 mg/kg bw : 40male and 40 female 500 mg/kg bw : 40male and 40 female 1500 mg/kg bw : 40male and 40 female After a nine-week test period, 24 males and 24 females from the control group, and 14 males and 14 females from each test group were used for teratogenicity studies; the remainder were used for the reproduction study.
Control animals:
yes
Details on study design:
No data available
Positive control:
No data available

Examinations

Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: yes - Time schedule: - Cage side observations checked in table [No.?] were included. DETAILED CLINICAL OBSERVATIONS: Yes / No / No data - Time schedule: BODY WEIGHT: Yes - Time schedule for examinations: FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): - Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes / No / No data - Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data - Time schedule for examinations: OTHER:
Oestrous cyclicity (parental animals):
No data available
Sperm parameters (parental animals):
No data available
Litter observations:
STANDARDISATION OF LITTERS- Performed on day 4 postpartum: [yes/no]- If yes, maximum of [...] pups/litter ([...]/sex/litter as nearly as possible); excess pups were killed and discarded. PARAMETERS EXAMINEDThe following parameters were examined in [F1 / F2 / F3] offspring:number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, were observed GROSS EXAMINATION OF DEAD PUPS:yes ASSESSMENT OF DEVELOPMENTAL NEUROTOXICITY:ASSESSMENT OF DEVELOPMENTAL IMMUNOTOXICITY:
Postmortem examinations (parental animals):
Postmortem examinations (Parent Animal)SACRIFICEYes, Autopsy did of parent ratsGROSS NECROPSY:No data availableHISTOPATHOLOGY / ORGAN WEIGHTS: No data available
Postmortem examinations (offspring):
Postmortem examinations (offspring)SACRIFICEF1,F2, F3 pups were sacrificed.GROSS NECROPSYYesHISTOPATHOLOGY / ORGAN WEIGTHSYes
Statistics:
No data available
Reproductive indices:
No data available
Offspring viability indices:
No data available

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
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
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed
Description (incidence and severity):
No treatment-related effects on reproductive function was observed

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
1 500 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
reproductive performance
Remarks on result:
other: No effects on fertility was 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:
no effects observed
Dermal irritation (if dermal study):
not specified
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
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:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
not specified

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not specified

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
1 500 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
viability
sexual maturation
mortality
body weight and weight gain
organ weights and organ / body weight ratios
Remarks on result:
other: No effects on reproductive parameters observed

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

Results: F2 generation

General toxicity (F2)

Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not specified
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
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:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
not specified

Developmental neurotoxicity (F2)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F2)

Developmental immunotoxicity:
not specified

Effect levels (F2)

Dose descriptor:
NOAEL
Generation:
F2
Effect level:
1 500 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
viability
sexual maturation
clinical signs
mortality
organ weights and organ / body weight ratios
Remarks on result:
other: No effects on reproductive parameters was observed

Target system / organ toxicity (F2)

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 at 3% (1500 mg/kg bw per day) for F0, F1 and F2 generation .When male and female wistar rats were treated with test material orally.
Executive summary:

A multigeneration reproductive toxicity study of test material was performed on male and female wistar rats. The test material mixed with feed in dose concentration 0, 0.1, 1.0 or 3% (0, 50, 500, 1500 mg/kg bw per day) and administered orally for three successive generations. Each generation having 60 animals of each sex in the control and 40 animals of each sex in test animals. No adverse effects were observed with respect to fertility, litter size and weight, general condition, male/female ratio, growth during lactation, survival or maturation. Autopsy of parent rats and pups at weaning did not reveal any treatment related changes in organ weights other than caecal enlargement in the 3% dose group. Gross and microscopic examination of the F3 generation at weaning did not reveal any abnormalities due to treatment and no adverse effects were seen in the teratology study. It was concluded that Brilliant Black PN did not exert any adverse effects on reproductive function of Wistar rats when fed at dietary levels up to 3% (1500 mg/kg bw per day) for three successive generations. Therefore, NOAEL was considered to be at 3% (1500 mg/kg bw per day) for F0 F1 and F2 generation .When male and female wistar rats were treated with test material orally.