2,4,6-trichloroaniline

Carcinogenicity

Description of key information

Carcinogenicity:

Chronic carcinogenicity study was performed to determine the carcinogenic nature of the test chemical. The study was performed using male rats for 24 months. The test chemical was mixed with feed at dose level of0, 3,000, or 6,000 ppm for 5 months followed by 0, 1,500 or 3,000 ppm for 13 months. Doses of 0, 79, or 303 mg/kg-day (based on time-weighted average concentrations of 0, 1,917, or 3,833 ppm) were calculated. Doses were lowered after 5 months of treatment; according to the study protocol, this action was taken either when there were treatment-related deaths or when body-weight gains in exposed animals were lower than corresponding controls by at least 10%. Rats were observed for up to 6 months after the end of the treatment period. Animals were monitored daily for mortality and clinical signs of toxicity. Body weights were recorded periodically. Complete necropsies were conducted on all animals that died after ≥6 months of treatment or at study termination. Histological examinations of grossly abnormal organs, tumor masses, the lung, liver, kidneys, spleen, adrenal, heart, bladder, stomach, intestines, reproductive organs, and pituitaries were performed. No significant increase in tumor incidence was observed in any group of rats. Based on the observations made, No observed adverse effect level (NOAEL) for male rats using 2, 4, 6 trichloroaniline is considered to be 303 mg/Kg/day since no significant increase in tumor incidence was observed in any group of rats.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data is from secondary literature

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

Chronic carcinogenicity study was performed to determine the carcinogenic nature of the test chemical

GLP compliance:

not specified

Species:

rat

Strain:

other: Charles River CD

Details on species / strain selection:

No data

Sex:

male

Details on test animals or test system and environmental conditions:

No data

Route of administration:

oral: feed

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: The test chemical was mixed with feed at dose level of 0, 3,000, or 6,000 ppm for 5 months followed by 0, 1,500 or 3,000 ppm for 13 months

DIET PREPARATION
- Rate of preparation of diet (frequency): No data
- Mixing appropriate amounts with (Type of food): No data
- Storage temperature of food: No data

VEHICLE
- Justification for use and choice of vehicle (if other than water): Feed
- Concentration in vehicle: 0, 79, or 303 mg/kg/day
- Amount of vehicle (if gavage): No data
- Lot/batch no. (if required): No data
- Purity: No data

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data

Duration of treatment / exposure:

24 months

Frequency of treatment:

Daily

Post exposure period:

6 months

Dose / conc.:

0 mg/kg bw (total dose)

Dose / conc.:

79 mg/kg bw (total dose)

Dose / conc.:

303 mg/kg bw (total dose)

No. of animals per sex per dose:

0 mg/Kg/day: 25 males
79 mg/Kg/day: 25 males
303 mg/Kg/day: 25 females

Control animals:

yes, concurrent vehicle

Details on study design:

No data

Positive control:

No data

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Daily
- Cage side observations checked in table [No.?] were included. Mortality

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily

DERMAL IRRITATION (if dermal study): No data
- Time schedule for examinations: No data

BODY WEIGHT: Yes
- Time schedule for examinations: Periodically

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

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

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations: No data

OPHTHALMOSCOPIC EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data

HAEMATOLOGY: No data
- Time schedule for collection of blood: No data
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. No data

CLINICAL CHEMISTRY: No data
- Time schedule for collection of blood: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. No data

URINALYSIS: No data
- Time schedule for collection of urine: No data
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked in table [No.?] were examined. No data

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

OTHER: No data

Sacrifice and pathology:

GROSS PATHOLOGY:
Yes, Complete necropsies were conducted on all animals that died after ≥6 months of treatment or at study termination.

HISTOPATHOLOGY:
Yes, Histological examinations of grossly abnormal organs, tumor masses, the lung, liver, kidneys, spleen, adrenal, heart, bladder, stomach, intestines, reproductive organs, and pituitaries were performed.

Other examinations:

No data

Statistics:

No data

Clinical signs:

not specified

Description (incidence and severity):

No detailed data available

Dermal irritation (if dermal study):

not specified

Mortality:

not specified

Description (incidence):

No detailed data available

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Dose descriptor:

NOAEL

Effect level:

303 mg/kg bw (total dose)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: No tumor incidence was observed

Critical effects observed:

not specified

Conclusions:

The No observed adverse effect level (NOAEL) for male rats using 2,4,6 trichloroaniline is considered to be 303 mg/Kg/day since no significant increase in tumor incidence was observed in any group of rats.

Executive summary:

Chronic carcinogenicity study was performed to determine the carcinogenic nature of the test chemical. The study was performed using male rats for 24 months. The test chemical was mixed with feed at dose level of0, 3,000, or 6,000 ppm for 5 months followed by 0, 1,500 or 3,000 ppm for 13 months. Doses of 0, 79, or 303 mg/kg-day (based on time-weighted average concentrations of 0, 1,917, or 3,833 ppm) were calculated. Doses were lowered after 5 months of treatment; according to the study protocol, this action was taken either when there were treatment-related deaths or when body-weight gains in exposed animals were lower than corresponding controls by at least 10%. Rats were observed for up to 6 months after the end of the treatment period. Animals were monitored daily for mortality and clinical signs of toxicity. Body weights were recorded periodically. Complete necropsies were conducted on all animals that died after ≥6 months of treatment or at study termination. Histological examinations of grossly abnormal organs, tumor masses, the lung, liver, kidneys, spleen, adrenal, heart, bladder, stomach, intestines, reproductive organs, and pituitaries were performed. No significant increase in tumor incidence was observed in any group of rats. Based on the observations made, No observed adverse effect level (NOAEL) for male rats using 2, 4, 6 trichloroaniline is considered to be 303 mg/Kg/day since no significant increase in tumor incidence was observed in any group of rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

303 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

Data is from secondary source

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the data available for the test chemical. the test chemical 2, 4, 6 trichloroaniline (CAS no 634 -93 -5) is not likely to be carcinogenic as per the criteria mentioned in CLP regulation.

Additional information

Carcinogenicity:

Data available for the test chemical was reviewed to determine the toxic nature of 2, 4, 6 trichloroaniline. The studies are as mentioned below:

Chronic carcinogenicity study was performed to determine the carcinogenic nature of the test chemical. The study was performed using male rats for 24 months. The test chemical was mixed with feed at dose level of0, 3,000, or 6,000 ppm for 5 months followed by 0, 1,500 or 3,000 ppm for 13 months. Doses of 0, 79, or 303 mg/kg-day (based on time-weighted average concentrations of 0, 1,917, or 3,833 ppm) were calculated. Doses were lowered after 5 months of treatment; according to the study protocol, this action was taken either when there were treatment-related deaths or when body-weight gains in exposed animals were lower than corresponding controls by at least 10%. Rats were observed for up to 6 months after the end of the treatment period. Animals were monitored daily for mortality and clinical signs of toxicity. Body weights were recorded periodically. Complete necropsies were conducted on all animals that died after ≥6 months of treatment or at study termination. Histological examinations of grossly abnormal organs, tumor masses, the lung, liver, kidneys, spleen, adrenal, heart, bladder, stomach, intestines, reproductive organs, and pituitaries were performed. No significant increase in tumor incidence was observed in any group of rats. Based on the observations made, No observed adverse effect level (NOAEL) for male rats using 2, 4, 6 trichloroaniline is considered to be 303 mg/Kg/day since no significant increase in tumor incidence was observed in any group of rats.

In another study, Chronic carcinogenicity study was performed to determine the carcinogenic nature of the test chemical. The study was performed using male rats for 18 months. The test chemical was mixed with feed at dose level of 0, 6,000, or 12,000 ppm (0, 1,040, or 2,070 mg/kg-day for female mice and 0, 1,030, or 2,060 mg/kg-day for male mice). Rats were observed for up to 6 months after the end of the treatment period. Animals were monitored daily for mortality and clinical signs of toxicity. Body weights were recorded periodically. Complete necropsies were conducted on all animals that died after ≥6 months of treatment or at study termination. Histological examinations of grossly abnormal organs, tumor masses, the lung, liver, kidneys, spleen, adrenal, heart, bladder, stomach, intestines, reproductive organs, and pituitaries were performed.No significant increase in tumor incidence was observed in either exposed group of female mice. However, a dose-related, statistically significant (p < 0.025 ) increase in the incidence of vascular tumors (not further characterized) was observed in dosed male mice (56 and 75% for the low- and high-dose groups, respectively) compared to concurrent controls (13%) and compared to pooled controls from similarly designed experiments. The incidence of hepatocellular carcinomas in male mice was statistically significantly (p < 0.025 ) increased in the low-dose group—but not the high-dose group—compared to the incidence in pooled, but not concurrent, controls (incidences in the pooled control, concurrent control, low-dose, and high-dose groups were 7/99, 1/16, 5/18, and 1/16, respectively).The lack of a dose-response relationship suggests that the effect was not treatment related.

The data summarized above is however inappropriate to judge the carcinogenic potential of the test chemical due to lack of chemicals.

Based on the data available for the test chemical. the test chemical 2, 4, 6 trichloroaniline is not likely to be carcinogenic as per the criteria mentioned in CLP regulation.