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

Endpoint summary

Description of key information

Repeated dose toxicity: oral
The No Observed Effect Level (NOEL) for 4-(phenylazo)benzene-1,3-diamine in rats is estimated to be 158.86 mg/Kg bw/day after repeated exposure via oral route, by OECD QSAR toolbox.

Repeated dose toxicity: inhalation
According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the substance 4-(phenylazo)benzene-1,3-diamine, which is reported as 0.00020265 Pa. Thus, exposure to inhalable dust, mist and vapour of the chemical 4-(phenylazo)benzene-1,3-diamine is highly unlikely. Therefore this study is considered for waiver.

Repeated dose toxicity: dermal
The acute toxicity value for 4-(phenylazo)benzene-1,3-diamine (as provided in section 7.2.3) is >2000 mg/kg body weight. Also, given the use of the chemical; repeated exposure by the dermal route is unlikely since the use of gloves is common practice in industries. Thus, it is expected that 4-(phenylazo)benzene-1,3-diamine shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that 4-(phenylazo)benzene-1,3-diamine shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: oral

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:

other: SD

Sex:

not specified

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

not specified

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

not specified

Frequency of treatment:

not specified

No. of animals per sex per dose:

not specified

Details on study design:

not specified

Positive control:

not specified

Observations and examinations performed and frequency:

not specified

Sacrifice and pathology:

not specified

Other examinations:

not specified

Statistics:

not specified

Clinical signs:

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

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Key result

Dose descriptor:

NOEL

Effect level:

158.865 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: no significant changes were noted at mentioned dose level

Critical effects observed:

not specified

The prediction was based on dataset comprised from the following descriptors: NOEL
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 ( not "i") )  )  and ("j" and "k" )  )

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 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: "g"

Referential boundary: The target chemical should be classified as No alert found OR SN1 >> Nitrenium Ion formation >> Aromatic nitro by DNA binding by OECD

Domain logical expression index: "h"

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

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.69

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.77

Conclusions:

The No Observed Effect Level (NOEL) for 4-(phenylazo)benzene-1,3-diamine in rats is estimated to be 158.86 mg/Kg bw/day after repeated exposure via oral route, by OECD QSAR toolbox.

Executive summary:

Repeated dose oral toxicity was evaluated for 4-(phenylazo)benzene-1,3-diamine using SSS QSAR prediction database V3.4. The study assumed the use of rats in a subacute study. Since no significant changes were noted, the No Observed Effect Level (NOEL) for 4-(phenylazo)benzene-1,3-diamine is estimated to be 158.86 mg/Kg bw/day.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

158.86 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Data is of K2 rating and is obtained from OECD QSAR toolbox.

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: dermal

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Repeated dose toxicity: oral
Predicted data for the substance 4-(phenylazo)benzene-1,3-diamine and its structurally related substance were reviewed for Repeated dose oral toxicity endpoint and are represented here as weight of evidence approach:

Repeated dose oral toxicity was evaluated for 4-(phenylazo)benzene-1,3-diamine using SSS QSAR prediction database V3.4. The study assumed the use of rats in a subacute study. Since no significant changes were noted, the No Observed Effect Level (NOEL) for 4-(phenylazo)benzene-1,3-diamine is estimated to be 158.86 mg/Kg bw/day.

The subacute repeated dose toxicity study of structurally related substance 2-chloro-p-phenylenediamine (CAS No. 615-66-7) in female Sprague-Dawley rats was conducted to evaluate the adverse effects by oral route (obtained from Fd Chem. Toxic. Vol. 22, no. 2, pp. I47 149, 1984). The test chemical was administered by oral gavage in the concentration of 100, 200 and 400 mg/kg/day. The results showed reduction in mean body weight gain of 200 and 400 mg/kg/day treated rats. No mortality were observed. Clinical signs was not observed. In addition, statistically significant increase in the number of resorptions was observed in 400 mg/kg/day treated female rats as compared to control.  No changes were observed in gross pathology of treated rats as compared to control. Thus, the no-observed adverse effect level (NOAEL) of 2-chloro-p-phenylenedi amine (o-chloro-p-PD) (CAS No. 615-66-7) in rats was considered to be 200 mg/kg/day.

Considering above data and by applying weight of evidence approach it can be concluded that the substance 4-(phenylazo)benzene-1,3-diamine will not show any effects on the specific target organ and is not toxic on Repeated exposure and hence it is considered to be not classified on Repeated exposure via oral route 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 will not show any effects on the specific target organ and is not toxic on Repeated exposure and hence it is considered to be not classified on Repeated exposure via oral route as per CLP regulation.