Registration Dossier

Toxicological information

Carcinogenicity

Currently viewing:

Administrative data

Description of key information

In a 2-year cancer study on male and female F344/N rats and B6C3F1 hybrid mice, groups of 50 males and 50 females were given 1,2-dichlorobenzene doses of 60 or 120 mg/kg/day by gavage for 103 weeks (5 days/week). Survivals of female rats and mice were comparable to those of the corresponding vehicle controls, but survival of high dose male rats was (p < 0.001) shorter than that of the vehicle controls. In this group there were three accidental deaths and five deaths probably due to the gavage process; in addition aspiration of 1,2-dichlorobenzene in corn oil into the lungs may have been a contributing factor to the deaths of 12 high dose male rats. Regarding neoplastic lesions the incidence of phaeochromocytoma of the adrenal gland in low dose male rats was elevated (p < 0.05) relative to controls. However, the incidence in the high dose group was lower than that of the controls and the dose-response trend was not statistically significant. Therefore, the increase in phaeochromocytoma in the low dose male rats is not regarded as related to administration of 1,2-dichlorobenzene. A dose-related increase (p < 0.05) in malignant histiocytic lymphoma was observed in male and female mice. However, comparison of the numbers of animals with all types of lymphomas is considered to be a more appropriate comparison. 1,2-dichlorobenzene did not increase the incidence of all types of lymphomas (combined) in male or female mice. Therefore, the increase in histiocytic lymphomas was discounted.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
carcinogenicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Guideline study with acceptable restrictions (only 2 instead of three dose levels; no differential blood count was performed; some tissues/organs not microscopally examined; no blood smear test; body weights not recorded and/or not reported according to guideline; food consumption not reported)
Reason / purpose:
reference to other study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 451 (Carcinogenicity Studies)
Deviations:
yes
Remarks:
; only 2 instead of three dose levels; no differential blood count was performed; some tissues/organs not microscopally examined; no blood smear test; body weights not recorded and/or not reported according to guideline; food consumption not reported
GLP compliance:
not specified
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Portage, MI
- Age at study initiation: 4 week old plus 17 days of acclimation period
- Housing: five animals/polycarbonate cage
- Diet (e.g. ad libitum): Purina Lab Chow 3/79 to 10/79; Zeigler Bros. N1N07 10/79 to 3/81 (ad libitum)
- Water (e.g. ad libitum): Edstrom automatic watering system, Waterford, WI (ad libitum)
- Acclimation period: 17 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23°C
- Humidity (%): 40-60%
- Air changes (per hr): 15 room air changes/hour
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
- Amount of dosage (if gavage): 5 mL/kg bw
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
103 w
Frequency of treatment:
5 d/w
Post exposure period:
no data
Remarks:
Doses / Concentrations:
60 or 120 mg/kg bw/d
Basis:
actual ingested
No. of animals per sex per dose:
50 plus 15 sentinel animals/sex/dose
Control animals:
yes, concurrent vehicle
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily for mortality and morbidity

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: intermittently until month 18 and at monthly intervals thereafter

DERMAL IRRITATION (if dermal study): No

BODY WEIGHT: Yes
- Time schedule for examinations: by cage every week for the first 13 weeks and monthly thereafter

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

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: No

CLINICAL CHEMISTRY: No

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes; grossly visible lesions were performed on major tissues and organs.
HISTOPATHOLOGY: Yes; tissue masses, abnormal lymph nodes, skin, mandibular or mesentric lymph nodes, mammary gland, salivary gland, bone marrow, sternebrae, femur or vertebrae, thymus, trachea, lung and bronchi, heart, thyroid, parathyroid, esophagus, stomach, small intestine, colon, liver, pancreas, spleen, kidneys, adrenals, urinary bladder, prostate/testes or ovaries/uterus, brain, and pituitary were microscopally examined. Eyes , tigh muscle, and spinal cord were examined grossly at necropsy but were examined microscopally only if they were found to be grossly abnormal.
Statistics:
see "Any other information on materials and methods incl. tables"
Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Food efficiency:
not specified
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
CLINICAL SIGNS AND MORTALITY
Estimates of the probabilities of survival of vehicle control and dosed groups in these studies were calculated by the method of Kaplan and Meier (1958). The survival of high dose males was significantly reduced when compared with low dose (P=0.014) and control (P<0.001) groups. No other significant differences were observed. One high dose female, one vehicle control male, and five high dose male rats were accidentally killed because of gavage error. These animals were censored from the statistical analyses of survival at the date of death. In addition, small amounts of the dosing solution were found in the lungs of 3 control, 8 low dose, and 12 high dose male rats that died before the end of the study.
In a retrospective data audit probable gavage-related deaths were reported in 1 high dose female, 1 vehicle control male, 1 low dose male, and 5 high dose males. Possible gavage-related deaths were also suggested in 3 vehicle control males, 4 low dose males, 12 high dose males, 2 low dose females, and 5 high dose females. In male rats, 42/50 (84%) of the controls, 36/50 (72%) of the low dose, and 19/50 (38%) of the high dose group lived to the end of the study (104-105 weeks). In female rats, 31/50 (62%) of the controls, 33/50 (66%) of the low dose, and 32/50 (64%) of the high dose group lived to the end of the study (104-105 weeks). The survival incidences include one control male that died during the termination period of the study. For statistical purposes, this animal has been pooled with those killed at the end of the study.

BODY WEIGHT AND WEIGHT GAIN
Mean body weights of high dose male rats were slightly lower than those of the vehicle controls. Mean body weights of low dose and vehicle control male rats were comparable. After week 32, mean body weights of dosed female rats were higher than those of the controls.

HISTOPATHOLOGY: NON-NEOPLASTIC
Nonneoplastic lesions did not appear to be increased in the liver, kidney, bone marrow, spleen, thymus or other organs of male or female rats as a result of the administration of 1,2-dichlorobenzene.

HISTOPATHOLOGY: NEOPLASTIC (if applicable)
Adrenals: The incidence of pheochromocytomas in low dose male rats was increased when compared with controls (see Table 1). This increase was significant by the life table test but not by the incidental tumor test. Since this tumor is not generally regarded as life-threatening, the most appropriate analysis for it is the incidental tumor test. The incidence of pheochromocytomas was not increased in high dose males and did not occur with a significant dose-response trend. Moreover, no malignant pheochrornocytornas were observed in either of the dose groups.

Hematopoietic System: The incidence of undifferentiated leukemias was significantly lower in the low dose females than that in the controls (see Table 2), but the incidence in the high dose females was the same as that in the controls. Moreover, there were differences between the incidence of rats with all types of leukemia in the dosed versus control groups. No differences were observed between, control and dosed male rats (10/50, 7/50, 5/50).

Testis: Interstitial-cell tumors occurred with a statistically significant positive trend in the life table test and with a significant negative trend by the Cochran-Armitage test. No significant results were obtained by the incidental tumor test, which is the most appropriate test for the analysis of this generally nonfatal tumor.

Pancreatic Islets: The combined incidence of male rats with islet-cell adenomas or carcinomas occurred with a statistically significant negative trend by the Cochran-Armitage test; however, when survival, differences were taken into account, the trend was not significant. Results of pairwise comparisons between vehicle controls and dosed groups were not statistically significant.
Relevance of carcinogenic effects / potential:
Under the conditions of this 2-year study, there was no evidence of carcinogenicity of 1,2-dichlorobenzene for male and female F344/N rats receiving 60 or 120 mg/kg per day.
Dose descriptor:
NOAEL
Effect level:
> 120 mg/kg bw/day (actual dose received)
Sex:
male/female
Basis for effect level:
other: no treatment-related pathologies observed

Table 1: INCIDENCES OP MALE RATS WITH PHEOCHROMOCYTOMAS OF THE ADRENAL GLAND

Vehicle Control  60 mg/kg  120 mg/kg
  Overall Incidence 9/50 (18%) 16/50 (32%) 6/49 (12%)
  Adjusted Incidence 20.9% 40.5% 21.7%
Terminal Incidence 8/42 (19%) 13/36 (36%) 2/18 (11%)
  Life Table Test P=0.201 P=0.039 P=0.380
  Incidental Tumor Test P=0.499N P=0.070 P=0.420N
  Cochran-Armitage Trend Test Pr=0.285N  --  --
  Fisher Exact Test -- P=0.083 P=0.303N

Table 2: INCIDENCES OF FEMALE RATS WITH LEUKEMIA

   Vehicle Control  60 mg/kg  120 mg/kg
Undifferentiated Leukemia      
  Overall Incidence  12/50 (24%)  3/50 (6%)  12/50 (24%)
  Adjusted Incidence  28.5%  7.0%  32.9%
  Terminal Incidence  4/31 (13%)  0/33 (0%)  9/32 (28%)
  Life Table Test  P=0.532  P=0.020N  P=0.570
  Incidental Tumor Test  P=0.524  P=0.022N  P=0.567
  Cochran-Armitage Trend  P=0.552    
  Fisher Exact Test    P=0.011N  P=0.592N
       
 All Leukemias      
    Overall Incidence  31/50 (26%)  6/50 (12%)  12/50 (24%)
    Adjusted Incidence  31.2%  14.7%  32.9%
   Terminal Incidence  5/31 (19%)  2/33 (6%)  9/32 (28%)
    Life Table Test  P=0.469N P=0.083N   P=0.514N
    Incidental Tumor Test P=0.469N P=0.104N   P=0.528N
   Cochran-Armitage Trend  P=0.451N    
   Fisher Exact Test    P=0.062  P=0.500
Conclusions:
There was no evidence of carcinogenicity of 1,2-dichlorobenzene for male and female F344/N rats receiving 60 or 120 mg/kg per day.
Executive summary:

NTP report, 1985

A carcinogenicity study was conducted according to OECD Guideline 451. The study was considered as reliable with restrictions. Only two instead of three dose levels were used and nor a differential blood count neither a blood smear test was performed. Some tissues/organs were not microscopally examined. Body weights and food consumption were not recorded.

For 103 weeks, male and female F344/N rats (50 animals/sex/dose) were gavaged with daily doses of 60 or 120 mg 1,2-dichlorobenzene /kg bw five days per week. The following observations and examinations were conducted during and/or at the end of the study:

- cage side observation twice daily for mortality and morbidity,

- detailed clinical observations intermittently until month 18 and at monthly intervals thereafter,

- body weights by cage every week for the first 13 weeks and monthly thereafter,

- gross pathology of grossly visible lesions were performed on major tissues and organs and

- histopathology on several organs and tissues.

When pathology examination was completed, the slides, individual animal data records, and summary tables were sent to an independent quality assurance laboratory. The final diagnosis represented a consensus of contractor pathologists and the NTP Pathology Working Group.

Estimates of the probabilities of survival of vehicle control and dosed groups in these studies were calculated by the method of Kaplan and Meier (1958). The survival of high dose males was significantly reduced when compared with low dose (P=0.014) and control (P<0.001) groups. In male rats 42/50 (84%) of the controls, 36/50 (72%) of the low dose, and 19/50 (38%) of the high dose group lived to the end of the study (104-105 weeks). In female rats 31/50 (62%) of the controls, 33/50 (66%) of the low dose, and 32/50 (64%) of the high dose group lived to the end of the study (104-105 weeks). No other significant differences were observed.

Mean body weights of high dose male rats were slightly lower than those of the vehicle controls. Mean body weights of low dose and vehicle control male rats were comparable. After week 32, mean body weights of dosed female rats were higher than those of the controls.

Non-neoplastic lesions did not appear to be increased in the liver, kidney, bone marrow, spleen, thymus or other organs of male or female rats as a result of the administration of 1,2-dichlorobenzene.

The incidence of pheochromocytomas in low dose male rats was increased when compared with controls. This increase was significant by the life table test but not by the incidental tumor test. Since this tumor is not generally regarded as life-threatening, the most appropriate analysis for it is the incidental tumor test. The incidence of pheochromocytomas was not increased in high dose males and did not occur with a significant dose-response trend. Moreover, no malignant pheochrornocytornas were observed in either of the dose groups.

The incidence of undifferentiated leukemias was significantly lower in the low dose females than that in the controls, but the incidence in the high dose females was the same as that in the controls. Moreover, there were differences between the incidence of rats with all types of leukemia in the dosed versus control groups. No differences were observed between, control and dosed male rats (10/50, 7/50, 5/50).

Interstitial-cell tumors in testis occurred with a statistically significant positive trend in the life table test and with a significant negative trend by the Cochran-Armitage test. No significant results were obtained by the incidental tumor test, which is the most appropriate test for the analysis of this generally non-fatal tumor.

The combined incidence of male rats with islet-cell adenomas or carcinomas in the pancreas occurred with a statistically significant negative trend by the Cochran-Armitage test; however, when survival, differences were taken into account, the trend was not significant. Results of pairwise comparisons between vehicle controls and dosed groups were not statistically significant.

For carcinogenicity, a NOAEL of >120 mg/kg bw/day for male and female rats could be stated. For toxicity, a NOAEL of >120 mg/kg bw/day can be defined because no treatment-related pathologies were observed in male and female rats.

Under these conditions, there was no evidence of carcinogenicity of 1,2-dichlorobenzene for male and female F344/N rats receiving 60 or 120 mg/kg per day.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified.

Endpoint:
carcinogenicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Guideline study with acceptable restrictions (only 2 instead of three dose levels; no differential blood count was performed; some tissues/organs not microscopally examined; no blood smear test; body weights not recorded and/or not reported according to guideline; food consumption not reported)
Reason / purpose:
reference to other study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 451 (Carcinogenicity Studies)
Deviations:
yes
Remarks:
; only 2 instead of three dose levels; no differential blood count was performed; some tissues/organs not microscopally examined; no blood smear test; body weights not recorded and/or not reported according to guideline; food consumption not reported
GLP compliance:
not specified
Species:
mouse
Strain:
B6C3F1
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
- Amount of dosage (if gavage): 5 mL/kg bw
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
103 w
Frequency of treatment:
5 d/w
Post exposure period:
no data
Remarks:
Doses / Concentrations:
60 or 120 mg/kg bw/d
Basis:
actual ingested
No. of animals per sex per dose:
50 animals/sex/dose
Control animals:
yes, concurrent vehicle
Relevance of carcinogenic effects / potential:
Under the conditions of this 2-year study, there was no evidence of carcinogenicity of 1,2-dichlororbenzene for male and female B6C3F1 mice receiving 60 or 120 mg/kg per day.
Dose descriptor:
NOAEL
Effect level:
> 120 mg/kg bw/day (actual dose received)
Sex:
male/female
Basis for effect level:
other: no treatment-related pathologies observed
Dose descriptor:
NOAEL
Effect level:
> 120 mg/kg bw/day (actual dose received)
Sex:
female
Basis for effect level:
other: no treatment-related pathologies observed
Dose descriptor:
NOAEL
Effect level:
> 60 mg/kg bw/day (actual dose received)
Sex:
male
Basis for effect level:
other: histopathology: increased renal tubular regeneration

Survivals of the high dose male and female mice were comparable with those of controls. A dose-related increase in tubular regeneration in the kidneys of male mice (control, 17%; low dose, 24%; high dose, 35%) was the only non-neoplastic change observed in the 2-year studies. In the present study, doses of 1,2-dichlorobenzene which produced hepatotoxicity produced no hematological changes in mice after 13 weeks of dosing.

Survivals of mice were comparable to those of the corresponding vehicle controls.

Statistically significant positive trends (P<0.05) occurred in the incidences of male and female mice with malignant histiocytic lymphomas. However, the incidences of male and female mice with all types of malignant lymphoma were not statistically different from those in the controls. Since histiocytic lymphoma is a controversial diagnosis among different pathologists and since all types of lymphomas have the same histogenesis, an increase in this specific type of lymphoma in the absence of an increase in the total incidence of all types of lymphomas is not considered to be biologically significant or to be related to 1,2-dichlorobenzene.

An increase in alveolar/ bronchiolar carcinomas (control 4/50, 8%; low dose, 2/50, 4%; high dose, 10/50, 20%) in male mice (significant by the Cochran-Armitage test but not the life-table or incidental tumor test) was discounted because the combined incidence of male mice with alveolar / bronchiolar adenomas or carcinomas (control, 8/50, 16%; low dose, 8/50, 16%; high dose, 13/ 50, 26%) was not significantly greater than controls by any of the tests. There was a significant decrease in hepatocellular adenomas in high dose male mice (control 8/50, 16%; low dose, 5/49, 10%; high dose, 2/46, 4%). This decrease was accompanied by a negativ dose-response trend using the Cochran-Armitage test. However, the combined incidence of male mice with liver adenoma or carcinoma (control, 19/50, 38%; low dose, 14/49, 29%; high dose, 11/46, 24%) was statistically significant only by the life table test.

Conclusions:
Under the conditions of this 2-year study, there was no evidence of carcinogenicity of 1,2-dichlororbenzene for male and female B6C3F1 mice receiving 60 or 120 mg/kg per day.
Executive summary:

Under the conditions of this 2-year study, there was no evidence of carcinogenicity of 1,2-dichlororbenzene for male and female B6C3F1 mice receiving 60 or 120 mg/kg per day.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
125 mg/kg bw/day
Study duration:
chronic
Species:
other: rats and mice
Quality of whole database:
NTP carcinogenicity studies in rats and mice available

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

NTP report, 1985

Rats:

Under these conditions, there was no evidence of carcinogenicity of 1,2-dichlorobenzene for male and female F344/N rats receiving 60 or 120 mg/kg per day.

A carcinogenicity study was conducted according to OECD Guideline 451. The study was considered as reliable with restrictions. Only two instead of three dose levels were used and nor a differential blood count neither a blood smear test was performed. Some tissues/organs were not microscopically examined. Body weights and food consumption were not recorded.

For 103 weeks, male and female F344/N rats (50 animals/sex/dose) were gavaged with daily doses of 60 or 120 mg 1,2-dichlorobenzene /kg bw five days per week. The following observations and examinations were conducted during and/or at the end of the study:

- cage side observation twice daily for mortality and morbidity,

- detailed clinical observations intermittently until month 18 and at monthly intervals thereafter,

- body weights by cage every week for the first 13 weeks and monthly thereafter,

- gross pathology of grossly visible lesions were performed on major tissues and organs and

- histopathology on several organs and tissues.

When pathology examination was completed, the slides, individual animal data records, and summary tables were sent to an independent quality assurance laboratory. The final diagnosis represented a consensus of contractor pathologists and the NTP Pathology Working Group.

Estimates of the probabilities of survival of vehicle control and dosed groups in these studies were calculated by the method of Kaplan and Meier (1958). The survival of high dose males was significantly reduced when compared with low dose (P=0.014) and control (P<0.001) groups. In male rats 42/50 (84%) of the controls, 36/50 (72%) of the low dose, and 19/50 (38%) of the high dose group lived to the end of the study (104-105 weeks). In female rats 31/50 (62%) of the controls, 33/50 (66%) of the low dose, and 32/50 (64%) of the high dose group lived to the end of the study (104-105 weeks). No other significant differences were observed.

Mean body weights of high dose male rats were slightly lower than those of the vehicle controls. Mean body weights of low dose and vehicle control male rats were comparable. After week 32, mean body weights of dosed female rats were higher than those of the controls.

Non-neoplastic lesions did not appear to be increased in the liver, kidney, bone marrow, spleen, thymus or other organs of male or female rats as a result of the administration of 1,2-dichlorobenzene.

The incidence of pheochromocytomas in low dose male rats was increased when compared with controls. This increase was significant by the life table test but not by the incidental tumor test. Since this tumor is not generally regarded as life-threatening, the most appropriate analysis for it is the incidental tumor test. The incidence of pheochromocytomas was not increased in high dose males and did not occur with a significant dose-response trend. Moreover, no malignant pheochrornocytornas were observed in either of the dose groups.

The incidence of undifferentiated leukemias was significantly lower in the low dose females than that in the controls, but the incidence in the high dose females was the same as that in the controls. Moreover, there were differences between the incidence of rats with all types of leukemia in the dosed versus control groups. No differences were observed between, control and dosed male rats (10/50, 7/50, 5/50).

Interstitial-cell tumors in testis occurred with a statistically significant positive trend in the life table test and with a significant negative trend by the Cochran-Armitage test. No significant results were obtained by the incidental tumor test, which is the most appropriate test for the analysis of this generally non-fatal tumor.

The combined incidence of male rats with islet-cell adenomas or carcinomas in the pancreas occurred with a statistically significant negative trend by the Cochran-Armitage test; however, when survival, differences were taken into account, the trend was not significant. Results of pairwise comparisons between vehicle controls and dosed groups were not statistically significant.

For carcinogenicity, a NOAEL of >120 mg/kg bw/day for male and female rats could be stated. For toxicity, a NOAEL of >120 mg/kg bw/day can be defined because no treatment-related pathologies were observed in male and female rats.

Mice:

Under the conditions of this 2-year study, there was no evidence of carcinogenicity of 1,2-dichlororbenzene for male and female B6C3F1 mice receiving 60 or 120 mg/kg per day.

Survivals of the high dose male and female mice were comparable with those of controls. A dose-related increase in tubular regeneration in the kidneys of male mice (control, 17%; low dose, 24%; high dose, 35%) was the only non-neoplastic change observed in the 2-year studies. In the present study, doses of 1,2-dichlorobenzene which produced hepatotoxicity produced no hematological changes in mice after 13 weeks of dosing.

Survivals of mice were comparable to those of the corresponding vehicle controls.

Statistically significant positive trends (P<0.05) occurred in the incidences of male and female mice with malignant histiocytic lymphomas. However, the incidences of male and female mice with all types of malignant lymphoma were not statistically different from those in the controls. Since histiocytic lymphoma is a controversial diagnosis among different pathologists and since all types of lymphomas have the same histogenesis, an increase in this specific type of lymphoma in the absence of an increase in the total incidence of all types of lymphomas is not considered to be biologically significant or to be related to 1,2-dichlorobenzene.

An increase in alveolar/ bronchiolar carcinomas (control 4/50, 8%; low dose, 2/50, 4%; high dose, 10/50, 20%) in male mice (significant by the Cochran-Armitage test but not the life-table or incidental tumor test) was discounted because the combined incidence of male mice with alveolar / bronchiolar adenomas or carcinomas (control, 8/50, 16%; low dose, 8/50, 16%; high dose, 13/ 50, 26%) was not significantly greater than controls by any of the tests. There was a significant decrease in hepatocellular adenomas in high dose male mice (control 8/50, 16%; low dose, 5/49, 10%; high dose, 2/46, 4%). This decrease was accompanied by a negative dose-response trend using the Cochran-Armitage test. However, the combined incidence of male mice with liver adenoma or carcinoma (control, 19/50, 38%; low dose, 14/49, 29%; high dose, 11/46, 24%) was statistically significant only by the life table test.


Justification for selection of carcinogenicity via oral route endpoint:
NTP carcinogenicity studies in rats and mice available

Justification for classification or non-classification

Under the conditions of these two-year gavage studies, there was no evidence of carcinogenicity of 1,2-dichlorobenzene for male or female F344/N rats or B6C3F1 mice receiving 60 or 120 mg/kg/day.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified.