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Carcinogenicity

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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.