2-nitro-p-toluidine

Endpoint summary

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:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

KemI-Riskline database

GLP compliance:

not specified

Species:

rat

Strain:

not specified

Sex:

male/female

Route of administration:

oral: unspecified

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

4-week

Remarks:

Doses / Concentrations:
0 (controls), 40, 200 and 1000 mg/kg body weight
Basis:
no data

Control animals:

yes

Details on results:

2-nitro-4-methylaniline caused minor anaemia in the females and males, starting at doses of 200 mg/kg body weight and 1000 mg/kg body weight, respectively.In the highest dose group there was an increase in the liver weights in both sexes and the females also had increased kidney weights, but there was no histopathological correlate in either case

Dose descriptor:

NOEL

Effect level:

200 other: mg/kg body weight

Based on:

test mat.

Sex:

male

Dose descriptor:

NOEL

Effect level:

40 other: mg/kg body weight

Based on:

test mat.

Sex:

female

Critical effects observed:

not specified

Conclusions:

Repeated dose toxicity (4 weeks) value of 2-nitro-p-toluidine to male rat is found to be NOEL: 200 mg/kg body weight while to female rat it is found to be NOEL: 40 mg/kg body weight.

Executive summary:

On 4-week oral administration of 0 (controls), 40, 200 and 1000 mg/kg body weight to rats, 2-nitro-4-methylaniline (2-nitro-p-toluidine) caused minor anaemia in the females and males, starting at doses of 200 mg/kg body weight and 1000 mg/kg body weight, respectively. In the highest dose group there was an increase in the liver weights in both sexes and the females also had increased kidney weights, but there was no histopathological correlate in either case. The no effect levels (NOEL) are 200 mg/kg body weight and 40 mg/kg body weight for male and female rats, respectively.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Study duration:

subacute

Species:

rat

Quality of whole database:

The Kemi database is considered to be a reliable database.

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 2.3.

GLP compliance:

no

Species:

rat

Strain:

other: Albino, not further specified;Wistar;Crl:CD(SD)BR;F344/N;F344;Sprague-Dawley;Crl:(Wi)BR;Charles River;no data;CD

Sex:

male/female

Route of administration:

inhalation: vapour

Type of inhalation exposure:

not specified

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Control animals:

not specified

Dose descriptor:

other: "Effect LOEL"

Effect level:

205.871

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: Effect: Body weight decreased

Critical effects observed:

not specified

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

("a" and ("b" and "c" ) )

Domain logical expression index: "a"

Similarity boundary:Target: c1(OC)c(N)cc(N(=O)=O)cc1
Threshold=50%,
Dice(Atom pairs)

Domain logical expression index: "b"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.872

Domain logical expression index: "c"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.17

Conclusions:

The repeated dose toxicity LOEL (Lowest observed effect level) of 5-nitro-o-anisidine in rat was observed at a dose concentration of 205.8714 mg/kg bw/day by the inhalative route.This indicates that 5-nitro-o-anisidine shall not exhibit toxic effect to rat by the inhalative route below the above mentioned dose.

Executive summary:

The repeated dose toxicity LOEL (Lowest observed effect level) of 5-nitro-o-anisidine in rat was observed at a dose concentration of 205.8714 mg/kg bw/day by the inhalative route.This indicates that 5-nitro-o-anisidine shall not exhibit toxic effect to rat by the inhalative route below the above mentioned dose.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Study duration:

subacute

Species:

rat

Additional information

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
The Kemi database is considered to be a reliable database. The results indicated increase in the weight of liver and kidneys in male and female rats on repeated exposure to 2-nitro-p-toluidine in a 4 week study. The effects were observed above the dose of 200 mg/kg body weight.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
Model considered reliable by OECD. Decrease in the body weight was observed at the LOEL dose ranging between 117 to 205 mg/kg/day.