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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Endpoint:
repeated dose toxicity: oral, other
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Justification for type of information:
As m-toluidine hydrochloride dissociates into m-toluidine and hydrochloride the studies concerning the ecotoxicology of m-toludine are considered relevant for the registration according to REACH.

Data source

Reference
Reference Type:
publication
Title:
Screening-level hazard characterization: Monocyclic aromatic amines category
Author:
U.S. Environmental Protection Agency
Year:
2009
Bibliographic source:
U.S. Environmental Protection Agency, September 2009, pp1-32

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Sprague-Dawley rats (13/sex/dose) were administered m-toluidine via gavage at 0, 30, 100 and 300 mg/kg bw/d; males for 42 d, and females from 2 weeks prior to mating to day 3 of lactation (41-53 d)
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
m-toluidine
EC Number:
203-583-1
EC Name:
m-toluidine
Cas Number:
108-44-1
Molecular formula:
C7H9N
IUPAC Name:
m-toluidine
Test material form:
not specified

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
13 rates per sex and dose

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Duration of treatment / exposure:
males: 42 days
females: 41-53 days
Frequency of treatment:
once daily
Doses / concentrationsopen allclose all
Dose / conc.:
300 spores/kg bw/day (actual dose received)
Dose / conc.:
100 mg/kg bw/day (actual dose received)
Dose / conc.:
30 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
13
Control animals:
not specified
Details on study design:
In a combined repeated-dose/reproductive/developmental toxicity screening test, Sprague-Dawley rats (13/sex/dose) were administered m-toluidine via gavage at 0, 30, 100 and 300 mg/kg bw/d; males for 42 d, and females from 2 weeks prior to mating to day 3 of lactation (41-53 d).

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Mean bw gains during week 1 were significantly lower than controls in the 300 mg/kg bw/d males and the 100 and 300 mg/kg bw/d females. Signs of clinical toxicity, evidence sug-gestive of haemolytic anaemia (decreased erythrocyte counts and haemoglobin con-centration), and effects on various biochemical parameters were observed at 100 and 300 mg/kg bw/d. A statistically significant increase in relative kidney weight in high-dose males was observed. No other changes in organ weights were reported. Histopathological signs in the liver, spleen, and kidney were reported at varying de-grees of severity in both males and females ranging from slight to marked and oc-curring in some instances in a dose-response manner beginning at 100 mg/kg bw/d; signs of marked severity occurred only at 300 mg/kg bw/d. The histological changes reported in the liver and spleen (pigment deposit and extramedullary haematopoie-sis) were considered to be consistent with the reductions in erythrocyte counts and haemoglobin concentrations characteristic of haemolytic anaemia.
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Mean bw gains during week 1 were significantly lower than controls in the 300 mg/kg bw/d males and the 100 and 300 mg/kg bw/d females
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not examined
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
Signs of clinical toxicity, evidence sug-gestive of haemolytic anaemia (decreased erythrocyte counts and haemoglobin con-centration), and effects on various biochemical parameters were observed at 100 and 300 mg/kg bw/d.
Clinical biochemistry findings:
not examined
Endocrine findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not specified
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
A statistically significant increase in relative kidney weight in high-dose males was observed. No other changes in organ weights were reported.
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Histopathological signs in the liver, spleen, and kidney were reported at varying de-grees of severity in both males and females ranging from slight to marked and oc-curring in some instances in a dose-response manner beginning at 100 mg/kg bw/d; signs of marked severity occurred only at 300 mg/kg bw/d. The histological changes reported in the liver and spleen (pigment deposit and extramedullary haematopoie-sis) were considered to be consistent with the reductions in erythrocyte counts and haemoglobin concentrations characteristic of haemolytic anaemia.
Other effects:
not specified

Effect levels

open allclose all
Key result
Dose descriptor:
LOAEL
Effect level:
> 30 - <= 100 mg/kg bw/day (actual dose received)
Based on:
not specified
Sex:
male/female
Basis for effect level:
other: not specified
Key result
Dose descriptor:
NOAEL
Effect level:
30 mg/kg bw/day (actual dose received)
Based on:
not specified
Sex:
male/female
Basis for effect level:
other: not specified

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Signs of systemic toxicity in the adults consisted of the following: Mean bw gains during week 1 were significantly lower than controls in the 300 mg/kg bw/d males and the 100 and 300 mg/kg bw/d females. Signs of clinical toxicity, evidence sug-gestive of haemolytic anaemia (decreased erythrocyte counts and haemoglobin con-centration), and effects on various biochemical parameters were observed at 100 and 300 mg/kg bw/d. A statistically significant increase in relative kidney weight in high-dose males was observed. No other changes in organ weights were reported. Histopathological signs in the liver, spleen, and kidney were reported at varying de-grees of severity in both males and females ranging from slight to marked and oc-curring in some instances in a dose-response manner beginning at 100 mg/kg bw/d; signs of marked severity occurred only at 300 mg/kg bw/d. The histological changes reported in the liver and spleen (pigment deposit and extramedullary haematopoie-sis) were considered to be consistent with the reductions in erythrocyte counts and haemoglobin concentrations characteristic of haemolytic anaemia.
Executive summary:

As m-toluidine HCl dissociates into m-toluidine and hydrochloride the study is considered relevant for the registration according to REACH.


In a combined repeated-dose/reproductive/developmental toxicity screening test, Sprague-Dawley rats (13/sex/dose) were administered m-toluidine via gavage at 0, 30, 100 and 300 mg/kg bw/d; males for 42 d, and females from 2 weeks prior to mating to day 3 of lactation (41-53 d).


Signs of systemic toxicity in the adults consisted of the following: Mean bw gains during week 1 were significantly lower than controls in the 300 mg/kg bw/d males and the 100 and 300 mg/kg bw/d females. Signs of clinical toxicity, evidence sug-gestive of haemolytic anaemia (decreased erythrocyte counts and haemoglobin con-centration), and effects on various biochemical parameters were observed at 100 and 300 mg/kg bw/d. A statistically significant increase in relative kidney weight in high-dose males was observed. No other changes in organ weights were reported. Histopathological signs in the liver, spleen, and kidney were reported at varying de-grees of severity in both males and females ranging from slight to marked and oc-curring in some instances in a dose-response manner beginning at 100 mg/kg bw/d; signs of marked severity occurred only at 300 mg/kg bw/d. The histological changes reported in the liver and spleen (pigment deposit and extramedullary haematopoie-sis) were considered to be consistent with the reductions in erythrocyte counts and haemoglobin concentrations characteristic of haemolytic anaemia.


As the information has been published by the EPA and is publicly available, the studies have been rated as Klimisch 2.


Ths substance has not been classified according to GHS criteria.