Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

Toxicity to reproduction:
Since no significant changes were noted relating to effects on reproductive toxicity in rats, the No Observed Adverse Effect Level (NOAEL) for 4-(phenylazo)benzene-1,3-diamine is estimated to be 605.025 mg/Kg bw/day, by OECD QSAR toolbox.

Link to relevant study records
Reference
Endpoint:
toxicity to reproduction
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
Justification for type of information:
Data is predicted by OECD QSAR Toolbox version 3.4. The supporting QMRF report has been attached
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
Data is predicted by OECD QSAR Toolbox version 3.4 with logPow as the primary descriptor
GLP compliance:
not specified
Species:
rat
Strain:
not specified
Sex:
not specified
Route of administration:
oral: gavage
Vehicle:
not specified
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:
not specified
Frequency of treatment:
not specified
Details on study schedule:
not specified
No. of animals per sex per dose:
not specified
Details on study design:
not specified
Positive control:
not specified
Parental animals: Observations and examinations:
not specified
Oestrous cyclicity (parental animals):
not specified
Sperm parameters (parental animals):
not specified
Litter observations:
not specified
Postmortem examinations (parental animals):
not specified
Postmortem examinations (offspring):
not specified
Statistics:
not specified
Reproductive indices:
not specified
Offspring viability indices:
not specified
Clinical signs:
not specified
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: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed
Key result
Dose descriptor:
NOAEL
Effect level:
605.025 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
reproductive performance
other: no significant changes were noted at mentioned dose level
Remarks on result:
other: other details not specified
Critical effects observed:
not specified
Mortality / viability:
no mortality observed
Dose descriptor:
other: not specified
Remarks on result:
other: not specified
Critical effects observed:
not specified
Reproductive effects observed:
not specified

The prediction was based on dataset comprised from the following descriptors: NOAEL
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

((("a" or "b" or "c" or "d" or "e" )  and ("f" and ( not "g") )  )  and ("h" and "i" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anilines (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic azo AND SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Anilines by Protein binding by OASIS v1.4

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Anilines (amino-meta) AND Anilines (Unhindered) by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Moderate binder, NH2 group OR Non binder, MW>500 OR Weak binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.43

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is <= 6.84

Conclusions:
Since no significant changes were noted relating to effects on reproductive toxicity in rats, the No Observed Adverse Effect Level (NOAEL) for 4-(phenylazo)benzene-1,3-diamine is estimated to be 605.025 mg/Kg bw/day, by OECD QSAR toolbox.
Executive summary:

Toxicity to reproduction was evaluated for 4-(phenylazo)benzene-1,3-diamineu sing SSS QSAR prediction database V3.4. The study assumed the use of rats in a subacute study. Since no significant changes were noted relating to effects on reproductive toxicity in rats, the No Observed Adverse Effect Level (NOAEL) for 4-(phenylazo)benzene-1,3-diamine is estimated to be 605.025 mg/Kg bw/day.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
605.025 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Data is of K2 reliability and is obtained from OECD QSAR toolbox.
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Toxicity to reproduction:
Predicted data for the substance 4-(phenylazo)benzene-1,3-diamine and its read across substance were reviewed for toxicity to reproduction endpoint and are represented here as weight of evidence approach:

Toxicity to reproduction was evaluated for 4-(phenylazo)benzene-1,3-diamineu sing SSS QSAR prediction database V3.4. The study assumed the use of rats in a subacute study. Since no significant changes were noted relating to effects on reproductive toxicity in rats, the No Observed Adverse Effect Level (NOAEL) for 4-(phenylazo)benzene-1,3-diamine is estimated to be 605.025 mg/Kg bw/day.

In a reproductive toxicity study (Fd. Chem. Toxic. Vol. 22, no. 2, pp. I47 149, 1984), female Sprague-Dawley rat were exposed to structurally related substance 2-chloro-p-phenylenediamine (o-chloro-p-PD; CAS 615-66-7) orally in the concentration 0, 100, 200 and 400 mg/kg/day. In the parental generation, decreased in mean body weight were obsrved in 200 and 400 mg/kg/day treated rat as compared to control . In addition,significant increase in the number of resorptions were observed in female rat. Effect on fetal weight was observed when treated with 400 mg/kg/day. Therefore, NOAEL is considered to be 100 mg/kg/day for F0 generation and 200 mg/kg/day for F1 generation when rats are exposed to 2-chloro-p-phenylene diamine (o-chloro-p-PD) orally for 10 days.

Considering above data and by applying weight of evidence approach it can be concluded that the substance 4-(phenylazo)benzene-1,3-diamine did not showed any major effects on reproduction and hence it is considered to be not classified for Reproductive toxicity as per CLP regulation.

Justification for classification or non-classification

Considering above data and by applying weight of evidence approach it can be concluded that the substance 4-(phenylazo)benzene-1,3-diamine did not showed any major effects on reproduction and hence it is considered to be not classified for Reproductive toxicity as per CLP regulation.