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Toxicological information

Carcinogenicity

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Description of key information

Study not performed to any specified standard, however study data provided is clear and consice with reliable and plausible result.
NOAEL > 100 mg/kg (diet)

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:
supporting study
Study period:
Not stated
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Study not performed to any noted standard or to GLP.
Reason / purpose:
reference to same study
Qualifier:
no guideline followed
GLP compliance:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Species/strain: Wistar rats
Sex: male/female
Rats were held in metal cages in a heated and ventilated environment. Animals were segregated by sex and had free access to feed.
Route of administration:
oral: feed
Vehicle:
not specified
Details on exposure:
100 mg/kg of powdered feed
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data
Duration of treatment / exposure:
No data
Frequency of treatment:
24 months
Post exposure period:
No data
Remarks:
Doses / Concentrations:
100 mg/kg of powdered feed
Basis:
nominal in diet
No. of animals per sex per dose:
No. of animals: 40 rats in total, 20 males and 20 females
Control animals:
yes, concurrent no treatment
Details on study design:
Rats were held in metal cages in a heated and ventilated environment. Animals were segregated by sex and had free access to feed. All tissue specimens were stained with toluidene blue.
Six male animals died during the experiments and the other 14 animals were sacrificed at the end of the study. Three females were sacrificed for a preliminary report, one female died during the course of the experiment, and the remaining sixteen females were sacrificed at the end of the experiment. All of the autopsies performed on the animals were part of a complete histopathological study.
Reproduction evaluation:
Method: One male and five females from the 2-year carcinogenicity study were mated after seven months of treatment with 100 ppm of the test material. Their offspring (25 males and 27 females, first generation) were normal. Out of these 52 offspring of the first generation, 5 males and 5 females were treated with the test substance. These first generation rats were mated six months later to obtain a second generation. Their offspring (26 males and 22 females, second generation) were all normal. Of the 48 animals (second generation), 5 males and 5 females underwent treatment.
Positive control:
No data
Observations and examinations performed and frequency:
No data
Sacrifice and pathology:
All of the autopsies performed on the animals were part of a complete histopathological study.
Other examinations:
No data
Statistics:
No data
Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
no effects observed
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:
no effects observed
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined
Details on results:
Six male animals died during the experiments and the other 14 animals were sacrificed at the end of the study. Three females were sacrificed for a preliminary report, one female died during the course of the experiment, and the remaining sixteen females were sacrificed at the end of the experiment. All of the autopsies performed on the animals were part of a complete histopathological study.
Body weights and gross analysis did not show differences between control and treated rats.
Histological studies related to lungs, liver, spleen, pancreas, stomach, caecum, sigmoid and rectum, salivary glands, kidneys, uterus, ovaries, thyroid, thymus, lymphatic ganglions, heart and bone marrow revealed no abnormal developments.
No cardiac lesions were found.
Pulmonary Mycoplasmosis: A chronic mycoplasmic brancho-pneumopathy was seen in three of the animals and a chronic beginning bronchopneumonia on mycoplasmosis was seen in three of the animals. These pulmonary afflictions were also seen in the control animals.
Suppurative Otitis: A suppurative otitis without basilar abscess was seen in three animals. Meningeal diencephalons reactions were found in one animal which had suppurative otitis with basilar abcess. Similar findings were also seen in the control animals.
Digestive Tract: No lesions of the oesophagus or phrynx present. Intestinal valvulus observed.
Liver: Hepatic teatosis, hepatic inflammatory infiltration was found in two rats. Such hepatic afflictions are common in the control animals.
Spleen, Thymus, Lymphatic Ganglions: Spleen lymphoid hypertrophy, and splenitis was found in three rats. Similar spleen conditions were found in the control animals. No thymic lesions present. Mesentric cyst found in some rats. Similar findings occurred in the control animals.
Urinary Organs: Cystic nephrosis was found in three treated rats. Nephritis found in one rat. Similar conditions observed in the control animals.
Endocrine Glands: Cortico-suprarenal hypertrophy in 5 rats and hyperplasia on the hypophysis principal cells in 2 rats. Similar findings in control animals.
Male and Female Genital Organs: Testicular aplasia and epididymis inflammatory testicular infiltration found in a treated male rat. Similar findings occurred in control group. Hydrosalpinx, pyometra, congested uterus, benign ovarian cysts, benign mammary adenofibroid, atrophic genital tract and salient follicles were found in various treated females. Such findings were also found on the control females.
Reproduction evaluation: No teratogenic or congenital malformations are seen. All newborn animals from the second generation were carefully examined macroscopically. Autopsy was done on 10 animals of the first and second generation each. Neither the macropathological examination of the whole body nor the histopathology (lung, liver, spleen and kidney) showed any deviation from the normal morphology. There were no anomalies present in cranial-cerebral, digestive, thorax-visceral, abdnormal and genital studies.
Relevance of carcinogenic effects / potential:
Treatment with the test substance did not cause malignant tumours in wistar rats.
Dose descriptor:
other: Negative
Effect level:
> 100 mg/kg diet
Sex:
male/female
Basis for effect level:
other: Treatment with the test substance did not cause malignant tumours in wistar rats.
Remarks on result:
other: Effect type: carcinogenicity (migrated information)
Conclusions:
Treatment with the test substance did not cause malignant tumours in wistar rats.
Executive summary:

Study not conducted to any noted standards or in compliance with the Principles of Good Laboratory Practice (GLP).

Reproduction evaluation:

Method: One male and five females from the 2-year carcinogenicity study were mated after seven months of treatment with 100 ppm of the test material. Their offspring (25 males and 27 females, first generation) were normal. Out of these 52 offspring of the first generation, 5 males and 5 females were treated with the test substance. These first generation rats were mated six months later to obtain a second generation. Their offspring (26 males and 22 females, second generation) were all normal. Of the 48 animals (second generation), 5 males and 5 females underwent treatment.

 

Six male animals died during the experiments and the other 14 animals were sacrificed at the end of the study. Three females were sacrificed for a preliminary report, one female died during the course of the experiment, and the remaining sixteen females were sacrificed at the end of the experiment. All of the autopsies performed on the animals were part of a complete histopathological study.

 

Body weights and gross analysis did not show differences between control and treated rats.

Histological studies related to lungs, liver, spleen, pancreas, stomach, caecum, sigmoid and rectum, salivary glands, kidneys, uterus, ovaries, thyroid, thymus, lymphatic ganglions, heart and bone marrow revealed no abnormal developments.

No cardiac lesions were found.

Pulmonary Mycoplasmosis: A chronic mycoplasmic brancho-pneumopathy was seen in three of the animals and a chronic beginning bronchopneumonia on mycoplasmosis was seen in three of the animals. These pulmonary afflictions were also seen in the control animals.

Suppurative Otitis: A suppurative otitis without basilar abscess was seen in three animals. Meningeal diencephalons reactions were found in one animal which had suppurative otitis with basilar abcess. Similar findings were also seen in the control animals.

Digestive Tract: No lesions of the oesophagus or phrynx present. Intestinal valvulus observed.

Liver: Hepatic teatosis, hepatic inflammatory infiltration was found in two rats. Such hepatic afflictions are common in the control animals.

Spleen, Thymus, Lymphatic Ganglions: Spleen lymphoid hypertrophy, and splenitis was found in three rats. Similar spleen conditions were found in the control animals. No thymic lesions present. Mesentric cyst found in some rats. Similar findings occurred in the control animals.

Urinary Organs: Cystic nephrosis was found in three treated rats. Nephritis found in one rat. Similar conditions observed in the control animals.

Endocrine Glands: Cortico-suprarenal hypertrophy in 5 rats and hyperplasia on the hypophysis principal cells in 2 rats. Similar findings in control animals.

Male and Female Genital Organs: Testicular aplasia and epididymis inflammatory testicular infiltration found in a treated male rat. Similar findings occurred in control group. Hydrosalpinx, pyometra, congested uterus, benign ovarian cysts, benign mammary adenofibroid, atrophic genital tract and salient follicles were found in various treated females. Such findings were also found on the control females.

Reproduction evaluation: No teratogenic or congenital malformations are seen. All newborn animals from the second generation were carefully examined macroscopically. Autopsy was done on 10 animals of the first and second generation each. Neither the macropathological examination of the whole body nor the histopathology (lung, liver, spleen and kidney) showed any deviation from the normal morphology. There were no anomalies present in cranial-cerebral, digestive, thorax-visceral, abdnormal and genital studies.

 

Conclusion: Treatment with the test substance did not cause malignant tumours in wistar rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for selection of carcinogenicity via oral route endpoint:
Study not performed to any specified standard, however study data provided is clear and concise with reliable and plausible result.

Justification for classification or non-classification

Based on the data available the substance does not trigger any of the requirements for classification.

The registered substance is therefore not classified.