1-phenyl-3-(p-toluenesulfonyl)urea

Repeated dose toxicity: oral

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: data from ELINCS notification dossier approved by MSCA

Data source

Reference

Reference Type:

other: Body responsible for the test

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Directive 92/69/EEC, B.7

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1-phenyl-3-(p-toluenesulfonyl)urea

EC Number:

424-620-1

EC Name:

1-phenyl-3-(p-toluenesulfonyl)urea

Cas Number:

13909-63-2

Molecular formula:

C14H14N2O3S

IUPAC Name:

3-(4-methylbenzenesulfonyl)-1-phenylurea

Test animals

Species:

rat

Strain:

Sprague-Dawley

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

Method of administration: gavage

Duration of treatment / exposure:

Test duration: 28 days

Frequency of treatment:

Dosing regime: 7 days/week

No. of animals per sex per dose:

Male: 6 animals at 0 mg/kg bw/day
Male: 6 animals at 3 mg/kg bw/day
Male: 6 animals at 30 mg/kg bw/day
Male: 6 animals at 300 mg/kg bw/day
Female: 6 animals at 0 mg/kg bw/day
Female: 6 animals at 3 mg/kg bw/day
Female: 6 animals at 30 mg/kg bw/day
Female: 6 animals at 300 mg/kg bw/day

Results and discussion

Results of examinations

Body weight and weight changes:

effects observed, treatment-related

Details on results:

1) Clinical observations:
Mortality Data:
There were no death during the treatment and recovery periods.
Clinical observations:
Males and females dosed at 300 mg/kg/day showed treatment related effecxts including salivation, cyanosis, coloured urine, and coat staining.
Bodyweight:
A reduction in anticipated bodyweight gain was observed in males and females at 300 mg/kg/day.
Food consumption:
Decreased food consumption was noted in males and females dosed at 300 mg/kg/day.

2) Laboratory findings:
Haematology:
A reduction in mean corpuscular volume and increases in platelet count, reticulocyte count and leukjocyte count were detected in male rats
dosed at 300 mg/kg/day. Increased reticulocyte count was recognised in male and females from the 300 mg/kg/day recovery group,
and reducced haematocrit levels were noted in the males of this recovery group.
Blood chemistry:
Increases in GPT activity, gamma-GPT activity, bilirubin, urea nitrogen, total choloesterol, total protein and calcium, as well as a reduction on
A/G ratio were seen in male and female animals from the 300 mg/kg/day dose group. Increased alkaline phosphatase activity and declined
albumin level were also noted in males and females from the same dose group. n addition, serum colouration was recognised in this dose
group. Males from the 300 mg/kg/day recovery group showed increased bilirubin and urea nitrogen levels.
Urinanalysis:
Acidic urine was seen in males from the 300 mg/kg/day dose group. In urinary sediment, increases in disk or column-shaped yellow crystals
were detected in males and females from the 300 mg/kg/day dose group, In addition, increases in epithelial cells were noted in males from the
same dose group. These changes were not seen in the 300 mg/kg/day dose recovery group.

3) Effect in organs:
Necropsy:
Discolouration, scatteered haemorrhagic dots,brownish coloured areas, induration roughnes of surface and enlargement of the liver,
enlargement and dark reddish colour change of the spleen, atrophy of thymus, thickening of stomach mucosa, edema of glandular stomach
and haemorrhaic dots on the glndular stomach were noted in the 300 mg/kg/day dose at necropsy. In the 300 mg/kg/day dose recovery
group discolouration and roughness of the hepatic surface, and enlargement and dark reddish discolouration of the spleen were noted.
Oragn weights:
Absolute kidney weight decreases were noted in males from the 300 mg/kg/day dose group. Absolute liver weight increased in females dosed
at this level. Decreases in absolute kidney weight but increases in relative spleen weight were seen in males from the 300 mg/kg/day dose
recovery group. Increases in relative liver weights were seen in males and females from the 300 mg/kg/day dose group.
Histopathology:
Histopathological changes considered to be treatment-related noted in the 300 mg/kg/day dose group included multifocal necrosis of the liver,
bile duct hyperplasia, hyperplasia of the collecting duct, inflammatory cell infiltration in papillary interstitium, regenerative change of distal tubular
epithelium, and vacuolation of proximal tubular epithelium of the kidneys, increase of hemetopoietic cells in the spleen, and focal mucosal necrosis and edema of submucosal layer of the glandular stomach. Animals from the 300 mg/kg/day recovery group showed a tendency to recover from
hepatic abnormalities, and recovery in renal abnormalities after the 14-day treatment-free period. An increase in siderophores was seen in the
spleen. However, it is a cured picture seen after erythroclasis and shows a tendency toward healing of cythemolytic reactions themselves.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

30 mg/kg bw/day (nominal)

Basis for effect level:

other: original NCD unit is mg/kg/day.

2

Dose descriptor:

NOEL

Effect level:

30 mg/kg bw/day (nominal)

Basis for effect level:

other: original NCD unit is mg/kg/day.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Classified as Xn - harmful

Executive summary:

Serious effects on the health of the animal, as defined in Annex VI of Council Directive 67/548/EEC, were observed at the 300 mg/kg/day dose level, so it is considered necessary to classify the substance as "harmful".