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Toxicological information

Carcinogenicity

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Description of key information

The carcinogenicity of the test material has been addressed by using a weight of evidence approach. It has been determined that the test material is not carcinogenic, according to two in vivo studies and an abstract from a journal.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Link to relevant study records
Reference
Endpoint:
carcinogenicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
Not reported.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with generally accepted scientific principles, with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results.
Qualifier:
no guideline followed
Principles of method if other than guideline:
The carcinogenic potential of the test material was determined in a life-long study in mice. During the study, groups of 30 mice were exposed to dermal applications, three times a week, of test material as a 10% solution in benzene. Animal weights were recorded throughout the study and animals were observed for tumour formation. Remarkable signs were recorded and tumour incidences were compared to those of the vehicle controls. A positive control group was included to confirm the validity of the test method employed.
GLP compliance:
not specified
Species:
mouse
Strain:
Swiss
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Research Farms, Millerton N.Y
- Age at study initiation: 8 weeks old.
- Vaccinated against ectromelia.
- Housing: Metal cages with sterile wood chip. In groups of 10.
- Diet (e.g. ad libitum): Purina Laboratory Chow ad libitum.
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 72 to 76 °F.
- Air conditioned.
Route of administration:
dermal
Vehicle:
other: benzene
Details on exposure:
SITE PREPERATION:
The hair was clipped off the backs 2 days before the first treatment and as needed during the study.
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
Lifetime application.
Frequency of treatment:
3 times a week throughout lifetime.
Remarks:
Doses / Concentrations:
~ 100mg per application, at 10 % concentration.
Basis:
nominal conc.
No. of animals per sex per dose:
30 mice.
Control animals:
yes, concurrent vehicle
Details on study design:
PRELIMINARY TEST
- Preliminary short-term 2 week test were carried out to evaluate the toxicity of the test material.

MAIN TEST
- Animals were weighed regularly.
- Tumours recorded on appearance and scored according to Blandig et al.
- Paplillomas were recorded only if they persisted for more than 4 weeks, even if they subsequently regressed.
- Post mortem all tumours were harvested and confirmed microscopically.

CONTROL
- Controls: no treatment, benzene and acetone.
- 60 animals per group.
Positive control:
dibenz[a,h]anthracene
Observations and examinations performed and frequency:
- Animals were weighed regularly.
- Tumours recorded on appearance and scored according to Blandig et al.
- Paplillomas were recorded only if they persisted for more than 4 weeks, even if they subsequently regressed.
Sacrifice and pathology:
- Post mortem all tumours were harvested and confirmed microscopically.
Statistics:
no data
Clinical signs:
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
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
Description (incidence and severity):
No tumours were observed in test animals exposed to a 10% concentration of the test material.
Details on results:
No tumours were observed in test animals exposed to a 10% concentration of the test material.
Relevance of carcinogenic effects / potential:
Under the conditions of the study, the test material was not found to be carcinogenic when tested up to 10% in benzene.

Table 1. Results.

Cumulative No. Of mice with: Tumour Index
Concentration Median Survival time (days) Papilloma Carcinoma Total Malignant
10% 582 0 0 < 10 < 10
Conclusions:
In a lifetime study which exposed 30 mice to the test material at a 10% concentration, no tumours were reported.
Executive summary:

The carinogenicity of the test material was accessed in a lifetime study. Thirty mice were exposed three times per week to the test material at a concentration of 10 % in benzene. Under the conditions of the test no tumours were recorded.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Study duration:
chronic
Species:
mouse
Quality of whole database:
One dermal study is available; it was conducted to sound scientific principles with a good level of reporting. The study was assigned a reliability score of 2 accoding to Klimisch (1997) and considered suitable for assessment of the test material.

Additional information

Two in vivo studies, Van Duuren (1965 & 1967), have been provided which have reported there to be no carcinogenic effects caused by the test material. Van Duuren (1965) assessed the carcinogenicity of the test material in a lifetime dermal study. Thirty mice were exposed three times per week to the test material at a concentration of 10 % in benzene. Under the conditions of the test no tumours were recorded. Van Duuren (1967) assessed the carcinogenicity via subcutaneous injection in female Sprague-Dawley rats. No significant increase in tumour formation was observed as a result of exposure to 100 mg of the test material per 0.1ml of tricaprylin. Both studies were performed to sound scientific principles, with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results. They have thus been assigned a reliability score of 2, according to the principles for assessing data quality set out in Klimisch (1977).

Kotin (1963) provides a secondary review of a study which reported insignificant tumour formation. Thirty mice were exposed to 20 µM of the test material over an unspecified period of time. The secondary source has not been referenced. There is incomplete reporting of the methodology used and it is therefore not possible to assess the accuracy of the data. The study has been assigned a reliability score of 4, according to Klimisch (1977).

Alfa Aesar (2007) states that “Tumourigenic effects have been observed in tests with laboratory animals”, no reference has been provided for this data. It is not possible to assess the accuracy of this information and has therefore been assigned a reliability score of 4, according to Klimisch (1977).


Justification for selection of carcinogenicity via dermal route endpoint:
Only one dermal study is available.

Justification for classification or non-classification

Using a weight of evidence approach on the available data, the test material does not require classification as carcinogenic under Regulation 1272/2008.