2-chloroaniline

Repeated dose toxicity: oral

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

Reference

Reference 1

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 2

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 3

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 guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Remarks:

; no details on neurobehaviour, food efficiency or urinalysis

Test guideline 2

Qualifier:

equivalent or similar to guideline

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

Test material information

Constituent 1

Reference substance name:

2-chloroaniline

EC Number:

202-426-4

EC Name:

2-chloroaniline

Cas Number:

95-51-2

Molecular formula:

C6H6ClN

IUPAC Name:

2-chloroaniline

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 or test system 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.