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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
Data is from secondary source .

Data source

Referenceopen allclose all

Reference Type:
secondary source
Title:
Provisional Peer-Reviewed Toxicity Values for- 2,4,6-Trichloroaniline (CASRN 634-93-5) and 2,4,6-Trichloroaniline Hydrochloride (CASRN 33663-50-2)
Author:
SRC, Inc
Year:
2010
Bibliographic source:
Superfund Health Risk Technical Support Center National Center for Environmental Assessment Office of Research and Development U.S. Environmental Protection Agency Cincinnati, OH 45268
Reference Type:
publication
Title:
Hygienic standardization of 2,4,6-trichloroaniline in water
Author:
Sapegin, DI; Fomochkin, IP; Pis’ko, GT; et al.
Year:
1985
Bibliographic source:
Gig Sanit 3:83–84,1985

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: As mention below
Principles of method if other than guideline:
A chronic reproductive toxicity study of 2, 4, 6-trichloroaniline was conducted in white male and female rats by oral gavage.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2,4,6-trichloroaniline
EC Number:
211-219-8
EC Name:
2,4,6-trichloroaniline
Cas Number:
634-93-5
Molecular formula:
C6H4Cl3N
IUPAC Name:
2,4,6-trichloroaniline
Test material form:
solid
Details on test material:
-Name of the test material: 2,4,6-trichloroaniline
- Molecular formula: C6H4Cl3N
- Molecular weight: 196.464 g/mol
- Smiles notation: Nc1c(Cl)cc(Cl)cc1Cl
- InChl : 1/C6H4Cl3N/c7-3-1-4(8)6(10)5(9)2-3/h1-2H,10H2
-Substance type: Organic
-Physical state: solid

Test animals

Species:
rat
Strain:
not specified

Administration / exposure

Route of administration:
oral: gavage
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
Not specified.
Duration of treatment / exposure:
6 months
Frequency of treatment:
5days/week
Duration of test:
6 months
Doses / concentrations
Remarks:
0.4, 4, or 40 mg/kg-day, 5 days/week, for 6 months
(adjusted to 0.3, 3, or 29 mg/kg-day)
No. of animals per sex per dose:
120 males and 60 females
Control animals:
yes, concurrent vehicle
Details on study design:
Not specified

Examinations

Maternal examinations:
Clinical sign, histopathology were observed .
Ovaries and uterine content:
ovogenesis, (specific endpoints evaluated and methods utilized were not further specified)
Fetal examinations:
embryotoxicity, and teratogenicity were assessed(specific endpoints evaluated and methods utilized were not further specified)
Statistics:
Not specified
Indices:
Morphofunctional indices were observed.
Historical control data:
Not specified

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
mortality observed, treatment-related
Description (incidence):
Pre- and postimplantation fetal mortality and decreased numbers of dam were reported at the mid-dose(3 mg/kg/day) compare to control.
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
no effects observed
Description (incidence and severity):
The authors indicated that there were no significant variations in the “morphofunctional” indices (endpoints not specified) for the male and female reproductive organs.
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Massive hematomas were observed in the abdominal cavities of mid-dose (3 mg/kg/day) adult rats. The researchers did not indicate whether the effects reported for mid-dose
rats also(3 mg/kg/day) occurred in high-dose(29mg/kg/day) rats.
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Maternal developmental toxicity

Number of abortions:
not specified
Pre- and post-implantation loss:
not specified
Total litter losses by resorption:
not specified
Early or late resorptions:
not specified
Dead fetuses:
effects observed, treatment-related
Description (incidence and severity):
Pre- and postimplantation fetal mortality and decreased numbers of fetuses were reported at the mid-dose(3 mg/kg/day) compare to control.
Changes in pregnancy duration:
not specified
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified
Changes in number of pregnant:
not specified

Effect levels (maternal animals)

Key result
Dose descriptor:
NOAEL
Effect level:
0.3 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: No significant effect were observed at this dose .
Remarks on result:
other: No toxic effect were observed

Maternal abnormalities

Abnormalities:
not specified
Localisation:
not specified
Description (incidence and severity):
not specified

Results (fetuses)

Effect levels (fetuses)

Dose descriptor:
other: not specified
Based on:
not specified
Sex:
not specified
Basis for effect level:
other: not specified
Remarks on result:
other: not specified

Fetal abnormalities

Abnormalities:
not specified
Localisation:
other: not specified
Description (incidence and severity):
not specified

Overall developmental toxicity

Key result
Developmental effects observed:
yes
Lowest effective dose / conc.:
3 mg/kg bw/day
Treatment related:
yes
Relation to maternal toxicity:
not specified
Dose response relationship:
not specified
Relevant for humans:
no

Applicant's summary and conclusion

Conclusions:
A devlopmental NOAEL was considered to be 0.3 mg/kg/day for F1 generation when rats were treated with 2, 4, 6 trichloroaniline orally for 6 months.
Executive summary:

In a chronic reproductive toxicity study, white male and female rats were exposed to 2, 4, 6 trichloroanilinein the concentrations of 0, 0.3, 3 and 29 mg/kg/day by oral gavage. The results showed that 2, 4, 6 trichloroaniline is toxic at higher doses. Toxic changes were observed as decreased in weight gain,increased numbers of hypochromic RBCs and doubled levels of methemoglobin, Anisocytosis, poikilocytosis, reticulocytosis, hypochromia and presence of Heinz bodies in the RBCs and decreased in SDH and LDH activities in liver and the kidney of 29 mg/kg/day treated rat. Increased relative weights of brain and decreased liver weight. In addition, Degenerative changes and evidence of hemorrhage in the myocardium, kidneys, liver, spleen and brain in 29 mg/kg/day treated rats. Decreased numbers of fetuses/dam and massive hematomas were observed in abdominal cavities of 3 mg/kg/day treated rat of P0 generation. In F1 generation, Pre and postimplantation fetal mortality were also observed in 3 mg/kg/day treated rat. No teratogenic effect were observed at this dose .Therefore, NOAEL was considered to be 0.3 mg/kg/day in F1 generation,when rats were treated with 2, 4, 6 trichloroaniline orally for 6 months. This study is limited by inadequate data reporting, including the strain, size, and sex distribution of the control and treatment groups, the methods utilized,and the endpoints evaluated. Furter studies has to conducted to classify this substance.