N-acetylsulphanilyl chloride

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from authoritative database

Data source

Reference

Reference Type:

other: Authoritative database

Title:

Short term repeated dose toxicity study using the test chemical

Author:

J-Check

Year:

2003

Bibliographic source:

121-60-8_407

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Principles of method if other than guideline:

According to OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

N-acetylsulphanilyl chloride

EC Number:

204-485-1

EC Name:

N-acetylsulphanilyl chloride

Cas Number:

121-60-8

Molecular formula:

C8H8ClNO3S

IUPAC Name:

4-acetamidobenzenesulfonyl chloride

Test material form:

solid: crystalline

Details on test material:

- Name of test material (as cited in study report): N-acetylsulphanilyl chloride
- Substance type: Organic
- Physical state: solid

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Age at study initiation: 6 month old

Administration / exposure

Route of administration:

oral: gavage

Details on route of administration:

No Data Available

Vehicle:

olive oil

Details on oral exposure:

No Data Available

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No Data Available

Duration of treatment / exposure:

28 days with 2 weeks recovery period.

Frequency of treatment:

Daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day (nominal)

Remarks:

Control Group and Control Group Recovery

Doses / concentrations 2

Dose / conc.:

40 mg/kg bw/day (nominal)

Remarks:

Low Dose Group

Doses / concentrations 3

Dose / conc.:

200 mg/kg bw/day (nominal)

Remarks:

Mid Dose Group

Doses / concentrations 4

Dose / conc.:

1 000 mg/kg bw/day (nominal)

Remarks:

High Dose Group and High Dose Group Recovery

No. of animals per sex per dose:

6 animals of each sex per dose

Control animals:

yes, concurrent vehicle

Details on study design:

No Data Available

Positive control:

No Data Available

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: No Data Available

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: No Data Available

BODY WEIGHT: Yes
- Time schedule for examinations: No Data Available

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No Data Available
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No Data Available

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No Data Available

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not specified
- Time schedule for examinations: No Data Available

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: No Data Available
- Dose groups that were examined: No Data Available

HAEMATOLOGY: Yes
- Time schedule for collection of blood: No Data Available
- Anaesthetic used for blood collection: Not specified
- Animals fasted: Not specified
- How many animals: No Data Available

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: No Data Available
- Animals fasted: Not specified
- How many animals: No Data Available

URINALYSIS: Yes
- Time schedule for collection of urine: No Data Available
- Metabolism cages used for collection of urine: Not specified
- Animals fasted: Not specified

NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: No Data Available
- Dose groups that were examined: No Data Available
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No Data Available

IMMUNOLOGY: Not specified
- Time schedule for examinations: No Data Available
- How many animals: No Data Available
- Dose groups that were examined: No Data Available

OTHER: No Data Available

Sacrifice and pathology:

GROSS PATHOLOGY: Yes

HISTOPATHOLOGY: Yes

Other examinations:

No Data Available

Statistics:

No Data Available

Results and discussion

Results of examinations

Clinical signs:

effects observed, non-treatment-related

Description (incidence and severity):

No clinical signs were observed at all the dose groups, except few male animals that showed signs of salivation at high dose group. These signs were considered to be treatment related, since they were persistent till the last day of dosing and increased number of cases were observed by the end of the treatment. However, in recovery period these signs were reversed and no cases were noted with salivation. In female animals, transient cases of salivation and rales were observed, which were not considered to be treatment related.

Mortality:

no mortality observed

Description (incidence):

No mortality was observed in all the main groups and satellite/recovery group.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

No treatment related body weight changes were observed in both male and female rats during the course of administration of the test chemical. Also, normal body weight gain was observed in the animals of both the sexes in recovery group.

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

Food consumption was significantly and dose dependently decreased, when compared to the control group in both the sexes during the course of the treatment. This effect was reversed in the recovery period.

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

no effects observed

Description (incidence and severity):

No abnormal opthamological findings were observed in the test groups or recovery group, during and after the administration of the test chemical.

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

Hematological parameters such as PT, APTT, Differential leucocyte count, were affected due to the administration of the test chemical in both male and female animals. However, these effects were reversed during the recovery period.

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

At high dose changes in vital liver enzyme levels (AST, ALT) were observed. Also there was change in serum Electrolytes and Glucose were observed. However, all these effects were reversed during the recovery period.

Urinalysis findings:

effects observed, treatment-related

Description (incidence and severity):

Changes in urine parameters were observed mainly in males were observed due to the administration of the test chemical. Parameters were observed to be normal and within the range in case of females.

Behaviour (functional findings):

no effects observed

Description (incidence and severity):

No effects were observed in behavioural parameters in both male and females in neurobehavioural and functional observational battery during the course of administration of the test chemical.

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

Statistical significant difference in the weight of kidneys and thymus were observed in males and females due to the administration of the test chemical.

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

In the gross pathological parameters, the lumen of the cecum was observed to be dilatedin both male and female animals at high dose group. This effect was atributed to the administration of the test chemical. In recovery group males, one animal showed dilated renal pelvis in observation of kidneys, but this effect was not attributed to the administration of the test chemical. No other abnormal changes were observed in the females of recovery group.

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, non-treatment-related

Description (incidence and severity):

No effect due to the administration of the test chemical was observed in the histopathological examinations of all the observed tissues of various organs.

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Details on results:

No Data Available

Effect levels

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

behaviour (functional findings)

body weight and weight gain

clinical biochemistry

clinical signs

food consumption and compound intake

gross pathology

haematology

histopathology: non-neoplastic

mortality

ophthalmological examination

organ weights and organ / body weight ratios

urinalysis

Remarks on result:

not determinable due to absence of adverse toxic effects

Target system / organ toxicity

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

Based on all the available observations and results, it was concluded that the NOAEL of the test chemical was observed to be 1000 mg/kg/day in Crj: CD(SD) strain of rat by oral exposure in a repeated dose toxicity study.

Executive summary:

A study was conducted to assess the toxicity of the test chemical after repeated exposure for 28 days. The study was conducted according to OECD test guideline 407. The doses used for the study were 0, 40, 200 and 1000 mg/kg bw. Two satellite groups were included in the study as control group recovery (0 mg/kg bw) and high dose recovery (1000 mg/kg bw). 6 animals per sex were used per group. The test chemical was dissolved in olive oil. The animals were dosed for 28 days and the effects observed were as follows. No clinical signs were observed at all the dose groups, except few male animals that showed signs of salivation at high dose group. These signs were considered to be treatment related, since they were persistent till the last day of dosing and increased number of cases were observed by the end of the treatment. However, in recovery period these signs were reversed and no cases were noted with salivation. In female animals, transient cases of salivation and rales were observed, which were not considered to be treatment related. No mortality was observed in all the main groups and satellite/recovery group. No treatment related body weight changes were observed in both male and female rats during the course of administration of the test chemical. Also, normal body weight gain was observed in the animals of both the sexes in recovery group. Food consumption was significantly and dose dependently decreased, when compared to the control group in both the sexes during the course of the treatment. This effect was reversed in the recovery period. No abnormal opthamological findings were observed in the test groups or recovery group, during and after the administration of the test chemical. Hematological parameters such as PT, APTT, Differential leucocyte count, were affected due to the administration of the test chemical in both male and female animals. However, these effects were reversed during the recovery period. At high dose changes in vital liver enzyme levels (AST, ALT) were observed. Also there was change in serum Electrolytes and Glucose were observed. However, all these effects were reversed during the recovery period. Changes in urine parameters were observed mainly in males were observed due to the administration of the test chemical. Parameters were observed to be normal and within the range in case of females. No effects were observed in behavioural parameters in both male and females in neurobehavioural and functional observational battery during the course of administration of the test chemical. Statistical significant difference in the weight of kidneys and thymus were observed in males and females due to the administration of the test chemical. In the gross pathological parameters, the lumen of the cecum was observed to be dilatedin both male and female animals at high dose group. This effect was atributed to the administration of the test chemical. In recovery group males, one animal showed dilated renal pelvis in observation of kidneys, but this effect was not attributed to the administration of the test chemical. No other abnormal changes were observed in the females of recovery group. No effect due to the administration of the test chemical was observed in the histopathological examinations of all the observed tissues of various organs. Based on all the available observations and results, it was concluded that the NOAEL of the test chemical was observed to be 1000 mg/kg/day in Crj: CD(SD) strain of rat by oral exposure in a repeated dose toxicity study.