p-toluidine

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Original report not available, study on 4-isopropylaniline

Data source

Reference

Title:

4-Isopropylaniline (CAS-No. 88-99-7): Acute oral toxicity test, Combined repeat dose and reproductive/developmental toxicity screening test in rats, Reverse mutation assay in bacteria, Chromosomal aberration test in culturedmammalian cells.

Author:

MHW Japan (1999). Ministry of Health and Welfare.

Year:

1999

Bibliographic source:

Toxicity Testing Reports of Environmental Chemicals 7,323-353, 713-716, 726-737, 752-753.

Materials and methods

Principles of method if other than guideline:

Migrated dataset. Method: other: OECD Guide-line 422 (see freetext method)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

88-99-7

IUPAC Name:

88-99-7

Constituent 2

Reference substance name:

4-isopropylaniline

EC Number:

202-797-2

EC Name:

4-isopropylaniline

Cas Number:

99-88-7

IUPAC Name:

4-isopropylaniline

Details on test material:

IUCLID4 Test substance: other TS: 4-Isopropylaniline (CAS-No. 88-99-7): Purity: 99.27 %

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Administration / exposure

Route of administration:

oral: gavage

Duration of treatment / exposure:

males 48 days; females 15 days before mating, throughout pregnancy until day 3 of lactation

Frequency of treatment:

once daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 6, 20, 60 mg/kg bw/day dissolved in corn oil
Basis:

Control animals:

yes, concurrent vehicle

Details on study design:

Sex: male/female
Duration of test: 54 days

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

ca. 60 mg/kg bw/day

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

ca. 20 mg/kg bw/day

Basis for effect level:

other: teratogenicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

Migrated dataset;
Result: see freetext: Result
RS-Freetext:
Results from repeated dose toxicity study part:

1 female was found dead in the 60 mg/kg group at day 25 of gestation.
Anemic eyeballs and salivation were observed in the 20 mg/kg or more  groups in both sexes; palor in the 60 mg/kg  group was noted in females  during gestaion period.
Body weight gain (graphics only) showed a tendency for decrease in the 20  mg/kg or more groups in males and in the 60 mg/kg group in females during  gestation period.
Food consumption (graphics only) was decreased in the 60 mg/kg groups in  males during the early administration period.

Hematology of males revealed  methemoglobin increase in the 20 mg/kg or  more groups (1.2 % or 2.5% versus 0.7% in controls) 
Furthermore, in the 60 mg/kg male group, 
---Decrease:
HCT (40.7% versus 44.7% in controls), 
HGB (13.4g/dl versus 15.4 g/dl in controls, 
RBC (6.71 x10[exp.6]/mm³ versus 8.21 x10[exp.6]/mm³ in controls) 
MCHC (32.9% versus 34.4% in controls) 
---Increase:
MCV (60.8µm³ versus 54.5µm³ in controls
MCH (20.0 pg versus 18.7pg)
PLT (1281 x10[exp.6]/mm³ versus 1092 x10[exp.6]/mm³ in controls)
RC (110% versus 28% in controls) 

Increases in spleen weights in 
- males: in the 60 mg/kg group (absolut/relative): 1.22g/0.683g% versus  0.76g/0.142g% in controls  
- females: in the 20 mg/kg or more  (absolut/relative):
0.71g/0.231g%, 1.05g/0.351g% versus 0.51g/0.169g% in controls; 

Increases in liver weights
- males given 20 mg/kg bw or more (absolut/relative): 
15.82g/3.083g%, 16.39g/3.223g% versus 15.12g/2.815g% in controls
- females given 60 mg/kg bw (absolut/relative):
14.43g/4.832g% versus 12.85g/4.285g% in controls

As gross necropsy findings, blackening and enlargement of the spleen were  observed in 20 mg/kg or more groups  in both sexes.
As histological findings, increases in hematopoiesis in bone marrow,  congestion, deposites of pigment and extramedullary hematopoiesis in the  spleen were observed in 20 mg/kg or more groups in both sexes. In the  liver, extramedullary hematopoiesis was observed in 60 mg/kg males and in  the 20 mg/kg or more groups in females. Deposites of pigment and  hypertrophy of hepatocytes were observed in both sexes receiving 60 mg/kg  bw/day.

NOEL(systemic toxicity male, female): 6 mg/kg bw/day

Results from reproductive and developmental toxicity study part:

As for reproductive ability of parent animals, no adverse effects of the  substance were observed in either sex:
with respect to estrous cycle length, copulation index, fertility index,  implantation index, gestation index and duration of gestation period,  delivery index.

NOEL(parental toxicity): 60 mg/kg bw/day

With regard to the effects on neonates,
no effects on live birth index 
no effeccts on sex ratio
60 mg/kg bw-group: 
body weight of pups in both sexes decreased (no data) 
viability on day 4 of lactation decreased in males:
males: 85.7 % versus 96.4% in controls
females: 97,2% versus 95.1 % in controls

NOEL(developmental toxicity) 20 mg/kg bw/day