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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Developmental toxicity / teratogenicity

Currently viewing:

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
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 peer reviewed journal

Data source

Reference
Reference Type:
publication
Title:
Teratogenicity And Embryotoxicity Study Of Brown Ht In The Rat
Author:
D. Grant And I. F. Gaunt
Year:
1987
Bibliographic source:
Fd Chem. Toxic. Vol. 25, No. 12, pp. 1009-1011

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: as mentioned below
Principles of method if other than guideline:
Teratogenicity and Embryotoxicity Study of Brown Ht (CAS No.4553-89-3) orally in rat
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Disodium 4,4'-[[2,4-dihydroxy-5-(hydroxymethyl)-1,3-phenylene]bis(azo)]bisnaphthalene-1-sulphonate
EC Number:
224-924-0
EC Name:
Disodium 4,4'-[[2,4-dihydroxy-5-(hydroxymethyl)-1,3-phenylene]bis(azo)]bisnaphthalene-1-sulphonate
Cas Number:
4553-89-3
Molecular formula:
C27H20N4O9S2.2Na
IUPAC Name:
disodium 4,4'-[[2,4-dihydroxy-5-(hydroxymethyl)-1,3-phenylene]bis(azo)]bisnaphthalene-1-sulphonate
Test material form:
solid: particulate/powder
Details on test material:
- Name of test material (as cited in study report): Disodium 4,4’-(2,4-dihydroxy-5- hydroxymethyl-1,3-phenylene bis-azo) di- (naphthalene-1-sulfonate)
- Molecular formula: C27H20N4O9S2.2Na
- Molecular weight: 654.58 g/mol
- Substance type: Organic
- Physical state: Solid

Test animals

Species:
rat
Strain:
Wistar

Administration / exposure

Route of administration:
oral: gavage
Type of inhalation exposure (if applicable):
other: not applicable
Vehicle:
water
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
- M/F ratio per cage: 1:1
- Length of cohabitation: Overnight
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy Vaginal plug or sperm, referred to as day 0 of pregnancy
- Any other deviations from standard protocol: - Additional animals were treated at each dose level to replace those that failed to conceive.
Frequency of treatment:
Daily
Duration of test:
19 days
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 250, 500 and 1000 mg/kg/day
Basis:
no data
No. of animals per sex per dose:
Total: 120
0 mg/kg/day: 30 femle
250 mg/kg/day: 30 femle
500 mg/kg/day: 30 femle
1000 mg/kg/day: 30 femle
Control animals:
yes, concurrent vehicle

Examinations

Maternal examinations:
Body weight and Body weight gain, clinical sign and gross abnormalities were examined
Ovaries and uterine content:
corpora lutea, implantations , Pre- implantation losses, early and late resorption, Post- implantation losses and live fetous were examined
Statistics:
Stsatistical analysis were done by using Student’s t test for all parameters except for the number of females with post – implantation losses for which chi-square test were used.
Historical control data:
In preliminary study groups of 10 female rats received daily doses of Brown HT in the concentration of 0, 250, 500 and 1000 mg/kg bw/day for 19 consecutive days. In treated rates body-weight gain were similar in all groups and no signs of toxicity were observed throughout the period of treatment. The faeces of the treated animals were markedly brown, and at autopsy there was brown discoloration of lymph nodes, colon and caecum.

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No significant change was observed in body weight and body weight gain of treated female rat 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
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified

Maternal developmental toxicity

Number of abortions:
not specified
Pre- and post-implantation loss:
effects observed, treatment-related
Description (incidence and severity):
The numbers of females with post-implantation losses were increased in the treated groups although this loss did not increase with increasing dose and was not significantly different from control.
Total litter losses by resorption:
not specified
Early or late resorptions:
not specified
Dead fetuses:
not specified
Changes in pregnancy duration:
not specified
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified
Changes in number of pregnant:
not specified
Other effects:
no effects observed
Details on maternal toxic effects:
Details on maternal toxic effects:
Mortality: No data available

Clinical signs:Nodata avaialble

Body weight: No significant change was observed in body weight and body weight gain of treated female rat as compared to control.

Reproductive function: estrous cycle: No statistically significant differences were observed in the mean numbers of corpora lutea, implantations, pre- and post implantation losses and resorptions of treated female rats.

The numbers of females with post-implantation losses were increased in the treated groups although this loss did not increase with increasing dose and was not significantly different from control.

Reproductive performance: No significant effect was observed on number of live fetuses, foetal numbers and sex ratio of treated rat as compared to control.

Gross pathology: No data available

Effect levels (maternal animals)

Key result
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Fetal body weight changes:
no effects observed
Description (incidence and severity):
No statistically significant differences were observed in foetal weight of treated rats.
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not specified
Reduction in number of live offspring:
no effects observed
Description (incidence and severity):
No effect was observed on number of live fetuses of treated rat.
Changes in sex ratio:
not specified
Changes in litter size and weights:
not specified
Changes in postnatal survival:
not specified
External malformations:
not specified
Visceral malformations:
not specified
Other effects:
effects observed, treatment-related
Details on embryotoxic / teratogenic effects:
Details on embryotoxic / teratogenic effects:
Mortality:
No effect was observed on number of live fetuses of treated rat.

Body weight:
No statistically significant differences were observed in foetal weight of treated rats.

Reproductive performance:
No statistically significant differences were observed on sex ratio of fetuses of treated rat as compared to control.

Gross pathology:
When treated with 1000 mg/kg bw/day, Bicentral ossification of 1st sternebra, presences of Fourteenth ribs, One thoracic vertebra & ribs absent, Forelimb proximal phalanges ossified, Metacarpals ossified of third and fourth skeleton were observed in fetuses of treated rat.

When treated with 500 mg/kg bw/day, Bicentral ossification of 1st and 2nd sternebra, Small second sternebra, One thoracic vertebra & ribs absent and Incomplete ossification of supra-occipital of skeleton were observed in foetuses.

When treated with 250 mg/kg bw/day, Small second sternebra, presences of fourteenth ribs and Incomplete ossification of supra-occipital of skeleton were observed in foetuses.

Histopathology:
When treated with 250 mg/kg bw/day, Renal pelvis enlargement and exencephaly of the cerebrum with lateral ventricle dilation in a foetus were observed in soft-part of treated rat as compared to control.

Effect levels (fetuses)

Key result
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: fetotoxicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
NOAEL was considered to be 1000 mg/kg bw /day for F0 and F1 generation when Wistar female rats treated with Brown HT (Disodium 4,4'-[[2,4-dihydroxy-5-(hydroxymethyl)-1,3-phenylene]bis(azo)]bisnaphthalene-1-sulphonate).
Executive summary:

In aTeratogenicity and Embryotoxicity study,Wistar female rats treated with Brown HT (Disodium 4,4'-[[2,4-dihydroxy-5-(hydroxymethyl)-1,3-phenylene]bis(azo)]bisnaphthalene-1-sulphonate) in the concentration of 0, 250, 500 and 1000 mg/Kg bw/day. No significant changes were observed on body weight, mean numbers of corpora lutea, implantations, pre- and post implantation losses, resumptions,number of live fetuses,foetal numbers and sex ratio of treated female rat as compared to control.

The numbers of females with post-implantation losses were increased in the treated groups although this loss did not increase with increasing dose and was not significantly different from control.In addition, no effect was observed on number of live fetuses and foetal weight of treated female rats as compared to control. Ossified sternebrae, Bicentral ossification, Small second sternebra, presences of fourteenth ribs, One thoracic vertebra & ribs absent, forelimb proximal phalanges and Metacarpalsossified and incomplete ossification of supra-occipital gross changes were observed in foetus.Renal pelvis enlargement and exencephaly of the cerebrum with lateral ventricle dilation in a foetus were observed also observed in foetus.

The observed effects are minor deviations from normal and are of doubtful toxicological significance.

Therefore,NOAEL was considered to be 1000 mg/kg bw /day for F0 and F1 generation whenWistarfemale rats treated with Brown HT orally by gavage for 19 days.