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Diss Factsheets

Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
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 from secondary source

Data source

Reference
Reference Type:
other: J-check
Title:
Combined Repeat Dose and Reproductive / Developmental Toxicity Screening Test of test matrial by Oral Administration in Rats
Author:
National Institute of Technology and Evaluation
Year:
2018
Bibliographic source:
Japanese Chemical Collaborative Knowledge Database, 2018

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
other: OECD Test Guideline 422.
Principles of method if other than guideline:
Combined repeated dose toxicity study with reproduction and developmental screening of test material in rats
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
3-hydroxy-4-[(2-methyl-5-nitrophenyl)azo]-N-phenylnaphthalene-2-carboxamide
EC Number:
229-245-3
EC Name:
3-hydroxy-4-[(2-methyl-5-nitrophenyl)azo]-N-phenylnaphthalene-2-carboxamide
Cas Number:
6448-95-9
Molecular formula:
C24H18N4O4
IUPAC Name:
3-hydroxy-4-[(2-methyl-5-nitrophenyl)diazenyl]-N-phenyl-2-naphthamide
Details on test material:
- Name of test material (as cited in study report):C.I. Pigment Red 22- Molecular formula :C24H18N4O4- Molecular weight :426.43 g/mole - Substance type:Organic- Physical state:Solid- purity:> 99 %
Specific details on test material used for the study:
No data available

Test animals

Species:
rat
Strain:
other: Crj:CD(SD)IGS
Details on test animals or test system and environmental conditions:
No data available

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5 % Sodium carboxymethylcellulose mixed with 0.1 % Tween 80
Details on exposure:
Details on exposurePREPARATION OF DOSING SOLUTIONS: The test material mixed with 0.5 % Sodium carboxymethylcellulose mixed with 0.1 % Tween 80DIET PREPARATION- Rate of preparation of diet (frequency):No data available- Mixing appropriate amounts with (Type of food):No data available- Storage temperature of food:No data availableVEHICLE- Justification for use and choice of vehicle (if other than water): The test material mixed with 0.5 % Sodium carboxymethylcellulose mixed with 0.1 % Tween 80- Concentration in vehicle: 0 (vehicle), 100, 300, 1000 mg/kg- Amount of vehicle (if gavage):No data available- Lot/batch no. (if required):No data available- Purity:No data available
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
No data available
Duration of treatment / exposure:
Males, 37 daysFemales, from 14 days before mating to day 4 of lactation
Frequency of treatment:
Daily
Duration of test:
Approx 60 days
Doses / concentrations
Remarks:
0 (vehicle), 100, 300, 1000 mg/kg
No. of animals per sex per dose:
Total: 960 mg/kg bw/day: 12 male, 12 female 100 mg/kg bw/day: 12 male, 12 female 100 mg/kg bw/day: 12 male, 12 female 1000 mg/kg bw/day: 12 male, 12 female
Control animals:
yes, concurrent vehicle
Details on study design:
No data available

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes - Time schedule: - Cage side observations checked in table [No.?] were included. DETAILED CLINICAL OBSERVATIONS: Yes - Time schedule: BODY WEIGHT: Yes - Time schedule for examinations: FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes - 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: POST-MORTEM EXAMINATIONS: yes - Sacrifice on gestation day:day 5 of lactation - Organs examined: numbers of corpora lutea or implantations OTHER:
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes Examinations included: - Gravid uterus weight: No data - Number of corpora lutea: Yes - Number of implantations: Yes - Number of early resorptions: No data - Number of late resorptions: No data - Other:
Fetal examinations:
- External examinations: Yes: - Soft tissue examinations: Yes: [all per litter / half per litter / #? per litter ] / No / No data - Skeletal examinations: Yes: [all per litter / half per litter / #? per litter ] / No / No data - Head examinations: Yes: [all per litter / half per litter / #? per litter ] / No / No data
Statistics:
No data available
Indices:
reproductive parameters such as the mating index, the fertility index, the implantation index, the delivery index, the gestation index,the live birth index, the viability index were observed
Historical control data:
No data available

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
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:
effects observed, non-treatment-related
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Maternal developmental toxicity

Number of abortions:
no effects observed
Pre- and post-implantation loss:
no effects observed
Total litter losses by resorption:
no effects observed
Early or late resorptions:
no effects observed
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): no effects observed
Changes in number of pregnant:
not specified
Other effects:
not specified

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: overall no effects on reproductive parameters
Remarks on result:
other: overall no effects on reproductive parameters

Maternal abnormalities

Abnormalities:
not specified

Results (fetuses)

Fetal body weight changes:
no effects observed
Description (incidence and severity):
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
Changes in sex ratio:
not specified
Changes in litter size and weights:
not specified
Changes in postnatal survival:
not specified
External malformations:
no effects observed
Skeletal malformations:
not specified
Visceral malformations:
not specified
Other effects:
not specified

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
reduction in number of live offspring
external malformations
other: overall no effects on developmental parameters
Remarks on result:
other: overall no effects on developmental parameters

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified
Treatment related:
not specified
Relation to maternal toxicity:
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/day as no developmental toxic effects were observed ,when Crj:CD(SD)IGS male and female rats were treated with test material orally by gavage.
Executive summary:

In a combined repeated dose toxicity study with reproduction and developmental screening, of test material was performed according to OECD Test Guideline 422.Crj:CD(SD)IGS male and female rats were treated with test material in the concentration of 0, 100, 300, 1000 mg/kg bw/day in 0.5 % Sodium carboxymethylcellulose mixed with 0.1 % Tween 80 orally by gavage.12 male and 12 female were placed in each group.Males were exposed with test chemical for 37 days while Females, from 14 days before mating to day 4 of lactation.Clinical sign, body weight, food consumption were observed. On day 38 male rats were killed while female onday 5 of lactation.

 No effect on clinical sign, body weight, food consumption, haematology and clinical chemistry of treated rats as compared to control. Similarly, no significant effect on mating index, fertility index, numbers of corpora lutea or implantations, implantation index, delivery index, gestation index, gestation length, parturition or maternal behaviour were observed in treated rats. Increase in liver weight was observed in male and female rats. No gross pathological and histopathological changes were observed in treated rats. In addition, no significant effect on mating index, fertility index, numbers of corpora lutea or implantations implantation index, delivery index, gestation index, gestation length, parturition or maternal behaviour and numbers of offspring or live offspring, sex ratio, live birth index, viability index or body weights of offspring were observed. No gross pathological changes were observed in offspring as compared to control. Therefore, NOAEL was considered to be 1000 mg/kg bw/day ,when Crj:CD(SD)IGS male and female rats were treated with test material orally by gavage.