N-acetylsulphanilyl chloride

Endpoint summary

Description of key information

Repeated Dose Toxicity (Oral):

Based on all the available data, it was concluded that the test chemical did not show any adverse effects or systemic toxicity after repeated exposure to the test animals. Therefore, on the basis of all observations and results, it was concluded that the test chemical is not likely to classify under STOT-RE 1 or 2 category, as per the CLP criteria of classification and labelling.

Repeated Dose Toxicity (Inhalation):

A short term repeated inhalation toxicity study does not need to be conducted because exposure of humans via inhalation in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment. Also, the given test chemical has very low vapor pressure 3.34E-007 mm Hg at 25°C., so the potential for the generation of inhalable vapors is very low. The normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point for repeated inhalation toxicity was considered for waiver.

Repeated Dose Toxicity (Dermal):

A short term dermal toxicity study does not need to be conducted since the pH of the test chemical is 1.97, which indicates the test chemical is highly acidic in nature and is likely to be classified in 'Skin irritant Category 1' as per CLP criteria of classifcation and labeling. Therfore, this endpoint is considered as a 'Waiver'.

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

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

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

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

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

Dose / conc.:

0 mg/kg bw/day (nominal)

Remarks:

Control Group and Control Group Recovery

Dose / conc.:

40 mg/kg bw/day (nominal)

Remarks:

Low Dose Group

Dose / conc.:

200 mg/kg bw/day (nominal)

Remarks:

Mid Dose Group

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

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

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

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

Critical effects observed:

no

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Data is from a Klimisch 2 datasource and provides a robust study summary.

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

a short-term toxicity study does not need to be conducted because exposure of humans via inhalation in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

a short-term toxicity study does not need to be conducted because exposure of humans via inhalation in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: dermal

Data waiving:

exposure considerations

Justification for data waiving:

a short-term toxicity study does not need to be conducted because exposure of humans via the dermal route in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Repeated dose toxicity: dermal - local effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: dermal

Data waiving:

exposure considerations

Justification for data waiving:

a short-term toxicity study does not need to be conducted because exposure of humans via the dermal route in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Repeated Dose Toxicity (Oral):

The repeated dose toxicity data from the studies of the test chemical by oral route is as follows:

Study 1:

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.

Study 2:

The toxic properties of the test substance were assessed by a repeated dose 28-day oral toxicity study using male and female Sprague-Dawley (SD )rats.The test chemical was administered via gavage to 6 rats/sex at the dose level of 100, 300 and 1000 mg/kg for 28 consecutive days.Groups of 6 rats/sex were administered either 0 or 1000 mg/kg test chemical daily till the first scheduled sacrifice and kept for 14 days without treatment to detect delayed occurrence, or persistence of, or recovery from toxic effects.Control animals received sesame oil as vehicle. Rats were observed for mortality, general appearance and clinical signs daily. Body weight was measured on day 1 (before the first administration) on day 3 and twice weekly thereafter and on the day of sacrifice. Food consumption was measured once a week during administration and recovery periods.Urine was collected from male rats on day 22 and 13 days after administration and from females on days 26-27 and on day 12 after administration. The appearance and of urine were examined and pH, occult blood, protein, sugar, ketone body, bilirubin, urobilinogen specific gravity and sediment were recorded.At the time of necropsy, blood was collected from all control and treated rats for haematology and clinical biochemistry tests. Rats were observed for gross lesions and the brain, heart, thymus, liver, kidney, spleen, adrenal gland, testis, epididymis, and ovaries were weighed. All organs including male and female sexual organs were dissected and preserved for further histopathological examination. Paraffin embedded and hematoxylin-eosin stained specimens of rats from 0 and 1000 mg/kg groups were prepared and examined under microscope.No mortality andapparent treatment-related clinical sign was observed in the treatment and recovery groups.The body weights were comparable in control, treatment and recovery groups in both males and females. There was no significant difference in food consumption between control and dosed rats in both sexes. In male rats, urinalysis revealed significant increase in specific gravity and decreased pH in the 1000 mg/kg group. There were no significant alterations in any of the tested parameters in the recovery group. Similarly, urinalysis parameters were unaltered in females at all doses. The test chemical solution was acidic what is most probably the reason of decreased urine pH observed in the high-dose groups. In males, haematology test revealed significant but minimal decrease in lymphocytes in terms of white blood cell percentage at 1000 mg/kg. There was no significant change in lymphocytes in the recovery group and in females at all dose level. Blood clinical chemistry demonstrated significant alterations in some parameter, but the changes were inconclusive and minimal or withing the historical control range. The absolute and relative weights of brain, liver, kidney, spleen, heart, thymus, adrenal, testis and epididymides were comparable in administered, recovery and control groups. In females, significant decrease of relative weight of spleen was observed in all dosed group, but not in the recovery group. This was not associated with any histopathological abnormalities of the bone marrow hematopoietic cells and lymphoid tissues such as thymus, lymph nodes, and spleen. In addition, during necropsy mild dilatation of cecum was found in one male and one female in the 1000 mg/kg groups, which was treatment related. Histopathology revealed mild lesions in the lung, liver, pancreas, kidney and prostate in both control and 1000 mg/kg groups in both sexes. However, the incidence and severity of these alterations were sporadic and mild without dose-response, therefore they were considered incidental changes. In summary, the oral administration ofthe test substanceinduced slight change in urine properties at 1000 mg/kg in males, but it did not impair the function of urinary system as other urinary parameters did not change. In addition, no effects of the test substance were observed on general condition, body weight and food consumption. At necropsy, the dilatation of cecum was observed at 1000 mg/kg, which was treatment related. However, it did not induce gastrointestinal symptoms e.g. diarrhea suggesting the gastrointestinal functions are not affected. Moreover, dilatation of the cecum was not seen in the recovery group confirming its reversibility. In conclusion, the repeated oral administration ofthe test chemicaldid not produced detectable adverse alteration of morphology, functional capacity, growth, development, or lifespan of the target organism under defined conditions of exposure, when male and female SD rats were orally administered up to 1000 mg/kg bw/day for 28 days. Hence, the NOAEL was estimated as 1000 mg/kg, the No-Observed-Effect-level (NOEL) was 300 mg/kg.

Repeated Dose Toxicity (Inhalation):

A short term repeated inhalation toxicity study does not need to be conducted because exposure of humans via inhalation in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment. Also, the given test chemical has very low vapor pressure 3.34E-007 mmHg at 25°C., so the potential for the generation of inhalable vapors is very low. The normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point for repeated inhalation toxicity was considered for waiver.

Repeated Dose Toxicity (Dermal):

A short term dermal toxicity study does not need to be conducted since the pH of the test chemical is 1.97, which indicates the test chemical is highly acidic in nature and is likely to be classified in 'Skin irritant Category 1' as per CLP criteria of classifcation and labeling. Therfore, this endpoint is considered as a 'Waiver'.

Justification for classification or non-classification

Based on all the available data, it was concluded that the test chemical did not show any adverse effects or systemic toxicity after repeated exposure to the test animals by oral route. The exposure of the test chemical is not likely to be possible by dermal and inhalation route. Therefore, on the basis of all observations and results, it was concluded that the test chemical is not likely to classify under STOT-RE 1 or 2 category, as per the CLP criteria of classification and labelling.