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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

The substance 4-nitroaniline do not show any repeated dose toxicity.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Qualifier:
according to guideline
Guideline:
other:
Principles of method if other than guideline:
Data is from RTECS database
GLP compliance:
not specified
Species:
rat
Strain:
not specified
Sex:
not specified
Route of administration:
oral: unspecified
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
90D (intermittent)
Control animals:
not specified
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
changes in spleen Blood - changes in other cell count (unspecified)
Dose descriptor:
LOEL
Effect level:
2 700 mg/kg bw (total dose)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: effects :- Blood - methemoglobinemia-carboxyhemoglobin Blood - changes in spleen Blood - changes in other cell count (unspecified)
Critical effects observed:
not specified
Conclusions:
Repeated dose toxicity LOEL (TDLo - Lowest published toxic dose) of 4-nitroaniline to rodent (Rat) by the oral route was observed at dose concentration of 2700 mg/kg.This indicates that 4-nitroaniline shall not exhibit toxic effects to rat by the oral route below the above mentioned dose.
Executive summary:

Repeated dose toxicity LOEL (TDLo - Lowest published toxic dose) of 4-nitroaniline to Rodent - rat by the oral route was observed at dose concentration of 2700 mg/kg.This indicates that 4-nitroaniline shall not exhibit toxic effects to rat by the oral route below the above mentioned dose.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
2 700 mg/kg bw/day
Study duration:
chronic
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data is from an authoritative source and the process of obtaining the reprint that shall give legitimate access to the study is on-going.
Qualifier:
according to guideline
Guideline:
other:
Principles of method if other than guideline:
data obtained from Actor database
GLP compliance:
not specified
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
other: Aerosol
Details on inhalation exposure:
vehicle Aerosol derived by passing air over PNA dissolved in isopropanol and warmed.
Analytical verification of doses or concentrations:
not specified
Remarks:
Doses / Concentrations:
0, 10, 32, 80 mg/m3 (analytical)
Basis:
analytical conc.
No. of animals per sex per dose:
total no. of animals: 40
Control animals:
yes
Details on study design:
sub-acute exposure period: 6 hours per day, 5 days per weekcontrol group: yes, concurrent vehicle Aerosol derived by passing air over PNA
dissolved in isopropanol and warmed. Groups of 10 rats/sex/group were housed in stainless steel and glass chamber and exposed under whole
body conditions to one of three levels of test material. A vehicle control group was exposed to isopropanol in a similar fashion and treated similarly for evaluation. Chamber atmospheres and particle size were analytically determined. Dosing occurred 6h/d, 5d/wk for 4 consecutive weeks; animals
were observed daily for clinical signs, weighed weekly, food and water given ad libitum , serum chemistry (BUN, SGPT, SAP, GLU, ALB, T.Protein, Glob.,
Na, K, P, Ca, Cl) and hematology (Hgb, HCT, RBC, Methem., clot time,T/Differ. Leuko, red cell morph) parameters collected on day 0 and 28.
Ophthalmoscopic exams conducted on day 0 and 28. Organ weights (gonads, hrt, kid, lvr, lu, pit, spln, brain) recorded at termination; all animals
necropsied at term; microscopic evaluation of approx. 40 tissues and organs (including gonads) for all high dose and control rats; spleens examined for all lower dose animals. Statistical methods used included: Bartletts test
Dose descriptor:
NOAEC
Effect level:
10 mg/m³ air
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: non-significant elevation in blood methemoglobin,significant increases in mean spleen weight (both sexes), iron deposition and extramedullary hematopoiesis seen in spleens (both sexes)
Critical effects observed:
not specified
Conclusions:
The NOAEC (no observed adversed effect concentration) value observed was 10 mg/m³ air in rat by inhalation exposure in a subacute study conducted with 4-nitroaniline which shows non-significant elevation in blood methemoglobin.
Executive summary:

The NOAEC (no observed adversed effect concentration) value observed was 10 mg/m³ air in rat by inhalation exposure in a subacute study conducted with 4-nitroaniline which shows non-significant elevation in blood methemoglobin.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
10 mg/m³
Study duration:
subacute
Species:
rat

Additional information

Repeated dose toxicity oral:-

Repeated dose toxicity LOEL (TDLo - Lowest published toxic dose) of 4-nitroaniline to Rodent - rat by the oral route was observed at dose concentration of 2700 mg/kg.This indicates that 4-nitroaniline shall not exhibit toxic effects to rat by the oral route below the above mention dose.

Repeated dose toxicity inhalation:-

The NOAEL (no observed adversed effect level) value observed was 10 mg/m³ air in rat by inhalation exposure in a subacute study conducted with 4-nitroaniline which was shows non-significant elevation in blood methemoglobin.

Repeated dose toxicity dermal:-

In accordance with column 1 of Annex IX, repeated dose toxicity by the dermal route was considered for waiver since the results for the acute toxicity by the dermal route has already been provided as part of the Annex VIII requirement in the preseding section 7.2.3.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
LOEL value of 4-nitroaniline observed was 2700 mg/kg/day. Therefore NOAEL value of 4-nitroaniline is bound to be less than 2700 mg/kg/day.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
The NOAEC (no observed adversed effect concentration) value observed was 10 mg/m³ air in rat by inhalation exposure in a subacute study conducted with 4-nitroaniline which shows non-significant elevation in blood methemoglobin.

Justification for classification or non-classification