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Diss Factsheets

Toxicological information

Toxicity to reproduction

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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 from secondary source

Data source

Reference
Reference Type:
secondary source
Title:
Reproductive study of test material was performed on rats
Author:
National Institute of Health Sciences
Year:
2006
Bibliographic source:
National Institute of Health Sciences,

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 reproduction and developmental screening of test material in rats
GLP compliance:
not specified
Limit test:
no
Justification for study design:
No data available

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:
Crj: CD(SD)
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: 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
Details on mating procedure:
No data available
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data available
Duration of treatment / exposure:
Males, 37 daysFemales, from 14 days before mating to day 4 of lactation
Frequency of treatment:
Daily
Details on study schedule:
No data available
Doses / concentrations
Remarks:
Doses / Concentrations:0 (vehicle), 100, 300, 1000 mg/kgBasis:actual ingested
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
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): yes - Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data - Compound intake calculated as time-weighted averages from the consumption and body weight gain data: 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:
No data available
Postmortem examinations (parental animals):
SACRIFICE Males, day 38Females, day 5 of lactation GROSS NECROPSY: yes - Gross necropsy consisted of [external and internal examinations including the cervical, thoracic, and abdominal viscera.] HISTOPATHOLOGY / ORGAN WEIGHTS: yes The tissues indicated in Table [#] were prepared for microscopic examination and weighed, respectively.
Postmortem examinations (offspring):
SACRIFICE: yes - The F1 offspring not selected as parental animals and all F2 offspring were sacrificed at [#?] days of age. - These animals were subjected to postmortem examinations (macroscopic and/or microscopic examination) as follows: GROSS NECROPSY: yes numbers of offspring or live offspring, the sex ratio, the live birth index, the viability index or body weights,external features, clinical signs or necropsy findings for the offspring were noted HISTOPATHOLOGY / ORGAN WEIGTHS The tissues indicated in Table [#] were prepared for microscopic examination and weighed, respectively.
Statistics:
No data available
Reproductive indices:
mating index, the fertility, index, , the implantation index, the delivery index, gestation index, gestation length, parturition or maternal behavior were observed.
Offspring viability indices:
The live birth index, the viability index or body weights were observed.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Description (incidence and severity):
No effect observed in treated rats
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No effect on body weight of treated 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 rats 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 haematological findings of treated rats was observed as compared to control.
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, treatment-related
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
No histopathological changes were observed in treatd rats as compared to control.
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 effects on mating index, fertility index, numbers of corpora lutea or implantations, implantation index, delivery index, gestation index, gestation length, parturition or maternal behavior of treated rats were observed.

Details on results (P0)

Clinical signs: No effect observed in treated rats Body weight: No effect on body weight of treated rats was observed as compared to control.Food consumption: No effect on food consumption of treated treated rats were observed as copmatred to control. Haematology: No effect on haematology of treated treated rats were observed as copmatred to control.Clinical chemistry: No effect on clinical chemistry of treated treated rats were observed as copmatred to control.Reproductive performance: No effects on mating index, fertility index, numbers of corpora lutea or implantations, implantation index, delivery index, gestation index, gestation length, parturition or maternal behavior of treated rats were observed. Organ weights: In the 1000 mg/kg group, liver weights were increased in both male and female rats.Gross pathology: No gross pathological changes were observed in treatd rats as compared to control. Histopathology: No histopathological changes were observed in treatd rats as compared to control.

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
body weight and weight gain
food consumption and compound intake
haematology
organ weights and organ / body weight ratios
gross pathology
reproductive performance
other: No effects on reproductive parameters
Remarks on result:
other: No effects on reproductive parameters 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
Description (incidence and severity):
No clinical signs of toxicity were observed in offspring as compared to cotnrol.
Dermal irritation (if dermal study):
not specified
Mortality / viability:
no mortality observed
Description (incidence and severity):
No significant differences in numbers of offspring or live offspring were observed as compared to cotnrol.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No effect on body weight of offspring were observed as compared to cotnrol.
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 gorss pathological changes were observed in offspring as compared to cotnrol.
Histopathological findings:
not specified
Other effects:
not specified

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not specified

Details on results (F1)

Viability: No significant differences in numbers of offspring or live offspring were observed as compared to cotnrol.clinical signs: No clinical signs of toxicity were observed in offspring as compared to cotnrol.Body weight: No effect on body weight of offspring were observed as compared to cotnrol.Gross pathology: No gorss pathological changes were observed in offspring as compared to cotnrol.

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:
other: No effect on live offspring, sex ratio, live birth index, viability index or body weights gross pathology and histopathology
Remarks on result:
other: overall no developmental toxic effects were 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

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/day 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.