4-(phenylazo)benzene-1,3-diamine

Endpoint summary

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

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.