Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1988-05-05 to 1989-03 (revised 1991-11)
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-study according to OECD TG.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
Deviations:
no
Remarks:
however, deviations from the protocol occurred.
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
4-nitro-m-xylene
EC Number:
201-947-4
EC Name:
4-nitro-m-xylene
Cas Number:
89-87-2
Molecular formula:
C8H9NO2
IUPAC Name:
2,4-dimethyl-1-nitrobenzene

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
Continous dietary administration to rats for 28 days.
Frequency of treatment:
Continous treatment, feed was available ad libitum.
Doses / concentrations
Remarks:
Doses / Concentrations:
0 ppm, 100 ppm, 600 ppm, 3000 ppm
Basis:
nominal in diet
No. of animals per sex per dose:
5 male and 5 female rats per dose
Control animals:
yes, plain diet

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Effect level:
600 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: - At this dose (mid-dose) none of the parameters determined in the course of this study showed changes that were considered to be of toxicological significande - 600 ppm corresponds to an actual substance intake of about 60 mg/kg body weight per day.

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Changes observed were the following:

- slight growth retardation in the mid- and top-dose group, while the retardation in the mid-dose group was considered of no toxicological relevance, since it was only slight and not statistically significant

- increases in liver weight, accompanied by decreases in total protein and albumin content in plasma (top-dose)

- in males of the top-dose: decreases in red blood cell count and haemoglobin concentration, increased adrenals weight (top-dose)

- in females: increased spleen weight

Applicant's summary and conclusion

Conclusions:
It is concluded that the no-toxic effect level of 4-nitro-1,3-dimethylbenzol in the present study is 600 ppm in the diet. This level is equivalent to a nominal overall intake of about 60 mg/kg body weight per day.