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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Guideline study conducted in compliance with GLP regulations. Original report not available. Data, reliability and rationale adopted according to OECD SIDS (2003) (publicly available peer reviewed source). Study according to OECD 422 (all organs, but not hematology or biochemistry; no indication of MetHb in preliminary study).

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
2001
Reference Type:
secondary source
Title:
SIDS Initial Assessment Report for SIAM 13 (o-nitroaniline) November 6-9, 2001 Bern, Final July 2003.
Author:
OECD SIDS
Year:
2003
Bibliographic source:
UNEP Publications

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
Principles of method if other than guideline:
As part of a reprotoxicity study, the number of animals was 12 per sex at the beginning and 10 animals per sex were used to continue the reprotoxicity part of the study and the examinations.
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Remarks:
400
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Males: from 4 weeks prior to mating, during mating, gestation of the females: i.e: 9 weeks.
Females: from 4 weeks prior to mating, during mating, gestation and lactation periods until post-partum day 3. Approximately 9 weeks.
Frequency of treatment:
Daily (7 days a week)
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 50, 150, 450 mg/kg bw/day
Basis:
actual ingested
No. of animals per sex per dose:
12
Control animals:
yes, concurrent vehicle

Results and discussion

Results of examinations

Details on results:
CLINICAL SIGNS AND MORTALITY
The only signs related to treatment were piloerection, salivation and matted fur observed after treatment. Matted fur was also observed and clinical
signs performed at weekly intervals in males and females of the high-dose group. No cyanosis was seen as an indication of methemoglobinemia.

BODY WEIGHT AND WEIGHT GAIN
Statistically significant reduction in body weight (5-6%) were observed at different times in high and mid dose groups during the treatment.
A statistically significant reduction in terminal bodyweight was observed in high-dose males (6%) compared to controls.

ORGAN WEIGHTS
No differences were observed in absolute and relative organ weights of males.

GROSS PATHOLOGY/HISTOPATHOLOGY: NON-NEOPLASTIC
Macroscopic and microscopic observations of all organs, including spermatogenic cycle, did not reveal any treatment-related effects.

Effect levels

open allclose all
Dose descriptor:
NOEL
Effect level:
50 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LOAEL
Effect level:
150 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: body weight

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion