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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: acceptable, well documented publication, which meets basic scientific principles

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Comparative Gavage subchronic studies of o-chloroaniline and m-chloroaniline in F344 rats and B6C3F1 mice
Author:
Hejtmancik, MR
Year:
2002
Bibliographic source:
Toxicological science 69: 234-243
Reference Type:
publication
Title:
Comparative Gavage subchronic studies of o-chloroaniline (OCA) and m-chloroaniline (MCA) in F344 rats and B6C3F1 mice
Author:
Hejtmancik, MR et al.
Year:
1994
Bibliographic source:
the toxicologist 14 (1): 394
Reference Type:
publication
Title:
NTP Technical Report on comparative toxicity studies of o-, m-, and p-chloroaniline
Author:
Chhabra, RS
Year:
1998
Bibliographic source:
National Toxicology Program-Toxicity report series number 43

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)
Deviations:
yes
Remarks:
; no details on neurobehaviour, food efficiency or urinalysis
Qualifier:
equivalent or similar to
Guideline:
EU Method B.26 (Sub-Chronic Oral Toxicity Test: Repeated Dose 90-Day Oral Toxicity Study in Rodents)
Deviations:
yes
Remarks:
; no details on neurobehaviour, food efficiency or urinalysis
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Purity: 99.8 %
Doses were formulated for oral gavage in deionized water containing 0.1 N HCl. Doses were 0, 2, 4, 8, 16 and 32 mg/mL.
Stability under test conditions was verified and the dosing solutions were kept refrigerated.

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories (Raleigh, NC)
- Age at study initiation: approx 7 weeks

- Housing: individually housed in polycarbonate cages with hardwood chips as bedding
- Diet: NIH-07 ad libitum
- Water: tap water, ad libitum
- Acclimation period: 13-14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5-23.9
- Humidity (%): 35-65
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES for males (females): From: 1992-01-27 (28) To: 1992-04-28 (29)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: water with 0.1 N HCl
Details on oral exposure:
no data
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
GC-analysis, no further data
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
once per day, 5 days per week
Doses / concentrations
Remarks:
Doses / Concentrations:
10, 20, 40, 80 and 160 mg/kg
Basis:
actual ingested
No. of animals per sex per dose:
10 per sex and dose in the core study
extra 10 per sex and dose in clinical pathology group (satellite group)

Control animals:
yes, concurrent vehicle
Positive control:
no

Examinations

Observations and examinations performed and frequency:
Animals were observed twice daily and were weighed at the start of the study, weekly thereafter, and at necroscopy. Clinical observations were recorded weekly.
Sacrifice and pathology:
Complete necropsies were performed on all animals in the core studies. The following organs were weighed: heart, right kidney, liver, lungs, spleen, right testis and thymus.
Histopathological evaluations were performed on all animals in the vehicle control and 160 mg/kg groups. Gross lesions and tissues masses of mice in all lower dose groups were examined.
Other examinations:
Rats of the core group were evaluated at the end of the studies in cluding hematology parameters and clinical chemistry parameters. Sperm motility and vaginal cytology evaluations were performed.
In addition total blood for hematology and clinical chemistry evaluations was collected on days 3 and 23 from rats in the clinical pathology groups. The dead animals were discarded thereafter.
Statistics:
Parametric comparison according to Williams or Dunnett: Body and organ weights
nonparametric comparative procedure according to Shirley or Dunn: clinical pathology
Fisher exact test: histopathological findings

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
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:
effects observed, treatment-related
Clinical biochemistry findings:
effects observed, treatment-related
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
no effects observed
Details on results:
see remarks on results

Effect levels

Dose descriptor:
LOAEL
Effect level:
10 mg/kg bw/day (actual dose received)
Sex:
male/female
Basis for effect level:
other: clinical chemistry (methemoglobin formation)

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

There were no treatment related deaths.

Significant weight reduction was observed in the 160 mg/kg group (male)
General observations: transient tremors (160 mg/kg); dose
related increase of methemoglobin levels in all animals
(maximum ca. 2-2.5% on day 93, stronger in females);
increase in Heinz bodies and signs of an anemia
(high-dose groups).
Findings upon necropsy predominantly at 80 and 160 mg/kg in
the spleen: increased weights and dark-red color, increased
hematopoesis and erythropoesis.

Applicant's summary and conclusion

Executive summary:

Hejtmancik, 1994

o-Chloroaniline was tested in a 13 week oral gavage study on male and female Fischer 344 rats. There were no treatment related deaths. No NOEL could be established. A LOEL (methemoglobin formation) of 10 mg/kg body weight per day was determined. Significant weight reduction was observed in the 160 mg/kg group (male)
General observations were: transient tremors (160 mg/kg); dose
related increase of methemoglobin levels in all animals
(maximum ca. 2-2.5% on day 93, stronger in females);
increase in Heinz bodies and signs of an anemia
(high-dose groups). Findings upon necropsy  were predominantly at 80 and 160 mg/kg in
the spleen and included increased weights and dark-red color, increased
hematopoesis and erythropoesis.