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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study; original reference in Japanese, compilation of data from English summary and tables

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1999
Reference Type:
publication
Title:
N-(1,3-Dimethylbutyl)-N'-phenyl-1,4-phenylenediamine, CAS no.: 793-24-8
Author:
OECD SIDS
Year:
2005
Bibliographic source:
UNEP Publications 2005

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: Guideline for 28-day Repeat Dose Toxicity Testing of Chemicals (Japan)
Deviations:
no
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
N-1,3-dimethylbutyl-N'-phenyl-p-phenylenediamine
EC Number:
212-344-0
EC Name:
N-1,3-dimethylbutyl-N'-phenyl-p-phenylenediamine
Cas Number:
793-24-8
Molecular formula:
C18H24N2
IUPAC Name:
N-(1,3-dimethylbutyl)-N'-phenylbenzene-1,4-diamine
Details on test material:
test substance: 99 % purity

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
28 days; 14 days recovery period (control and 100mg/kg bw group only)
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 4, 20, 100 mg/kg bw/d
Basis:

No. of animals per sex per dose:
5 per sex and dose + (5 males and females control and 100 mg/kg bw recovery group)
Control animals:
yes, concurrent vehicle
Details on study design:
Post-exposure period: 14 days

Results and discussion

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
20 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: females: reversible peripotal fatty changes of the liver without an increase of liver weight, increaed total serum protein
Dose descriptor:
LOAEL
Remarks:
100 mg/kg bw
Effect level:
100 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: increase in relative liver weights accompanied by periportal fatty change, clinical chemistry and haematological parameters changed indicating an existing anaemia.

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

RS-Freetext:
TOXIC RESPONSE/EFFECTS BY DOSE LEVEL:
-Mortality and time to death: none
-Clinical signs: not reported
-Body weight gain: no effect
-Food consumption: not reported
-Clinical chemistry: 
20 mg/kg: females: at end of administration sig. increase of
total protein 
  (p<0.05); sig. decrease of inorganic phosphate (p<0.01)
100 mg/kg: males: at end of administrationsign. increase of
total protein, 
  creatinine, Ca, total cholesterol, sign. decrease of
albumin/globulin  
  (p<0.01); at end of recovery sign. increase of
triglyceride (p<0.05); 
females: at end of administration sign. increase of total
protein (p<0.01), 
  albumin (p<0.05); sig. decrease of inorganic phosphate
(p<0.05) 
-Haematology:
100 mg/kg: males: at end of administration sign. increase of
MCHC (p<0.01), 
  platelets (p<0.05); sign. decrease of hematocrit and MCHC
(p<0.01); 
  at end of recovery: sign. decrease of hemoglobin, MCV ,
MCH (p<0.05), 
  hematocrit (p<0.01); sign. increase of platelets (p<0.05)
females: at end of administration sign. increase of
platelets (p<0.01); 
  sign. decrease of hematocrit, hemoglobin, MCV, prothrombin
time, activated 
  partial thromboplastin time (p<0.01); at end of recovery:
sign. decrease of
  hemoglobin, MCH (p<0.01), hematocrit, MCV,  (p<0.05); 
-Urinanalysis: 100 mg/kg: both sexes protein increased
-Organ weights: 100 mg/kg: sign. increased relative liver
weights in males and females (p<0.01) at end of
administration; reversible during recovery, but for females
still sign. increase at end of recovery (p<0.05)
-Gross pathology: 100 mg/kg: reversible liver enlargement 2
males and 1 female
-Histopathology: periportal fatty change at end of
administration at 20 mg/kg for females and at 100 mg/kg for
both sexes, effect reversible during recovery

Applicant's summary and conclusion