Leucophor 1111X

Carcinogenicity

Description of key information

No carcinogenic potential

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

5 mg/kg bw/day

Study duration:

chronic

Species:

other: hamster and rat

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

According to the CLP Regulation (EC 1272/2008), 3.6 Carcinogenicity section, carcinogen means a substance, which induce cancer or increase its incidence. Substances, which have induced benign and malignant tumours in well performed experimental studies on animals are considered also to be presumed or suspected human carcinogens unless there is strong evidence that the mechanism of tumour formation is not relevant for humans. For the purpose of the classification for carcinogenicity, substances are allocated to one of two categories (known or presumed human carcinogens and Suspected human carcinogens) based on strength of evidence and additional considerations (weight of evidence). In certain instances, route-specific classification may be warranted, if it can be conclusively proved that no other route of exposure exhibits the hazard.

The chronic/carcinogenicity studies available did not provide any evidence of carcinogenicity.

In conclusion, the substance does not meet the criteria to be classified for carcinogenicity, according to the CLP Regulation (EC 1272/2008).

Additional information

Golden hamster were chosen to investigate the effects of prolonged oral administration of the analogue substance 07. One serie of 15 males and one serie of 15 females were treated for 24 months with 5 mg/kg/day of the test item in water. The evolution of the general condition and weight (systematic weighing all the animals every 15 days), of clinical behavior and the state of the hair system were recorded. The haematological examination was performed before sacrifice. A blood sample was taken for the electrophoretic examination. Animals spontaneously died or sacrificed were submitted to a complete autopsy and to histological examination. The results of examinations were compared with the effects observed in 80 animals used as control and placed under the same environmental and semi-synthetic alimentary conditions.

In order to study the reproductive function in treated animals, a treated male was mated with 5 treated females. The mating resulted in 30 newborns of normal constitution; 5 males and 5 females of these 30 newborns were selected for the successive experimental step (none died spontaneously during the experiment). They did not present any abnormalities. Furthermore, a male of the fisrt generation treated with the test item was mated with 5 treated females of the first generation. This mating resulted in 26 newborns of normal constitution. 5 males and 5 females of the second generation were chosen for the study. They grew up normally and they did not present any abnormalities.

No signs of leukemia were recorded in the animals and all of them present normal leukocyte and electrophoretic formulas. Four animals died spontaneously before the end of the experiment.No animals present subcutaneous or liver sarcoma; none of the treated animals presented pituitary tumour. No animals presented testicular tumour. Testicular atrophy was notedin 3 animals; the same processes were observed also in the control animals. No females presented ovarian or uterine tumours. Ovarian hypertrophy was observed in only one animal; uterine hypertrophy was not recorded. Pulmonary hyperplasia tumouriforme was recorded in one female and the same process was observed in control animals. Pulmonary emphysema, without inflammatory reactions, was recorded in two males and in four females.

A hepatitis zonal processes was observed in one female; hepatic inflammatory phenomena were recorded in two males and in two females.

Spleen reactions were recorded in one male and in one female. Nephrosis were found in eight animals (four males and four females) and such phenomena were also observed in the control animals. No signs of leukemia were recorded in the animals.

No malignant tumour was recorded in 30 animals treated, thus the test item resulted to be non carcinogenic. Furthermore, the investigated substance did not promote the malignant tumour development, which were observed in the control animals. No signs of the reproductive impairments were observed and no teratogenic reactions were recorded. The test item did not shown the capability to induce visceral damage (Mosinger, 1966).

A further investigation was performed administering the same substance for 24 months to 30 Winstar rats at 5 mg/kg/day. The purpose of the investigation was examine the evolution of the general condition and of the clinical behaviour. Animals were submitted to a complete autopsy and a complete histological examination was performed. The reproductive function was assessed studying the first and the second generation. Sarcomatous malignant tumour was identified in one animal as a reticulo-sarcoma. A breast adenoma, pituitary adenoma and benign testicular tumours in two animals were also recorded. The test item did not show any carcinogenic potential; it did not cause more malignant tumours than those spontaneously observed in control animals (Mosinger).