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Carcinogenicity

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Description of key information

There was not a treatment related increase in stomach tumor incidence (papilloma and carcinoma) in rats orally exposed to 1000 mg/kg/day of 
gaiacol when compared to controls in a study described by Hirose et al. (1989). Therefore no NOAEL can be identified for carcinogenic effect.

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:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The purity of the test substance was known. The protocol was described in details. The results concerning the forestomach and the glandular stomach were detailed but the other organs were not examined. The GLP were not mentioned.
Qualifier:
according to guideline
Guideline:
OECD Guideline 451 (Carcinogenicity Studies)
Deviations:
yes
Remarks:
only male were tested, only 1 dose instead of 3, small number of animals (16 instead of 50), and for 51 weeks (instead of 2 years). Moreover only forestomach and glandular stomach were examined.
GLP compliance:
not specified
Species:
rat
Strain:
Fischer 344
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS:
- Source: Charles River Japan, Inc., Atsugi, Japan.
- Age at study initiation: 6 weeks old
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: 4 to 5 in plastic cage with wood chips for bedding
- Diet: Oriental MF basal diet (Oriental Yeast Co., Tokyo, Japan), ad libitum
- Water: tap water, ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS:
- Temperature (°C): 22-24°C
- Humidity (%): no data
- Air changes (per hr): air-conditioned room
- Photoperiod: 12h dark / 12h light

IN-LIFE DATES: no data
Route of administration:
oral: feed
Vehicle:
not specified
Details on exposure:
- Diet preparation
Rate of preparation of diet (frequency): once a month
Mixing appropriate amounts with (Type of food): Oriental M powdered diet
Storage temperature of food: no data
- Vehicle: none
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
For 51 weeks
Frequency of treatment:
no data
Post exposure period:
no data
Remarks:
Doses / Concentrations:
1000 mg/kg bw/ day (estimated by calculation)
Basis:
nominal in diet
No. of animals per sex per dose:
16
Control animals:
yes, concurrent no treatment
Observations and examinations performed and frequency:
- body weights of animals and food consumption were measured once every 2 or 4 weeks.
- Cage side observations: No data
- Detailed clinical observations: No
Time schedule for examinations of morbidity and mortality: rats becoming moribund were killed for necropsy and all surviving animals were
sacrified under ether anesthesia at the end of week 52.
- Body weight: Yes
Time schedule for examinations: every 2 or 4 weeks
- Food consumption and compound intake: 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
- Ophthalmoscopic examination: no data
- Haematology: no data
- Clinical chemistry: no data
- Urinalysis: no data
- Neurobehaviour: no data
- Organ weights: no data
Sacrifice and pathology:
Sacrifice and pathology:
- Gross pathology: yes
- Histopathology: yes
Other examinations:
Stomach, esophagus, intestines, liver, and kidney were removed. The liver and kidneys being weighed and fixed in 10% buffered formalin solution. The esophagus, stomach, and intestines were injected with formalin and later opened via an incision along the greater curvature. After fixation, six
sections each were cut from the anterior and posterior walls of the forestomach and glandular stomach.
Tissues were processed routinely for histopathological examination.
Animals which survived until the end of experiment were included in the effective numbers.
Statistics:
Student's test and Fisher's exact test were used for statistical evaluation of the data.
Body weight and weight changes:
no effects observed
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Details on results:
Mild and moderate forestomach hyperplasia was found in 93.8% of the rats received guaiacol but papilloma and carcinoma were not detected.
Forestomach lesions were focal and characterized by downward basal cell growth.
However, no glandular stomach lesions in fundic or pyloric region were observed in rats given guaiacol. The authors concluded that guaiacol did not enhance forestomach and glandular stomach carcinogenesis.
Dose descriptor:
NOAEL
Sex:
male
Remarks on result:
not determinable
Remarks:
no NOAEL identified. Effect type:carcinogenicity (migrated information)

Summary of the study with other chemical agents:

Modifying effects of resorcinol, hydroquinone, p-tert-butylcatechol(PTBC), p-methylcatechol (PMC), and o-methylcatechol (guaiacol) on N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)-induced forestomach and glandular stomach carcinogenesis were investigated in F344 rats. Groups of 15 to 16 male 6-wk-old animals were given a single intragastric administration of 150 mg/kg of body weight of MNNG and starting 1 wk later were administered  powdered diet containing 0.8% resorcinol, 0.8% hydroquinone, 1.5% PTBC, 1.5% o-methylcatechol (guaiacol), 1.5% PMC, or basal diet alone for 51 wk. Additional groups of 10 to 15 rats each were treated with the phenolic compounds or received basal diet without prior carcinogen exposure. Histological examination after sacrificeat Wk 52 revealed that squamous cell carcinoma development in the forestomachs of rats treated with MNNG followed by PTBC (75%, P 0.001) or MNNG followed by PMC (100%, P 0.001) was significantly greater than in animals receiving MNNG alone (20%). Treatment with PMC alone also resulted in a 40% yield of papilloma. In the glandular stomach, incidences of adenomatous hyperplasias in rats treated with MNNG followed by PTBC (31.3%, P 0.05) or PMC (100%, P 0.001) and the incidence of adenocarcinomas in rats treated with MNNG followed by PMC (100%, P 0.001) were significantly higher than in controls. In addition, PMC alone induced a 100% yield of adenomatous hyperplasias and 6.7% of adenocarcinomas. Thus, the results demonstrated that PTBC and PMC treatment significantly enhances forestomach and glandular stomach carcinogenesis and that PMC itself may possess weak carcinogenic potential in these organs. The ortho-position appears to be important for this dihydroxybenzene activity

Conclusions:
No treatment related increase in stomach tumor incidence.
Executive summary:

In a carcinogenicity study (Hirose et al., 1989) 1.5% (corresponding to 1000 mg/kg bw/day) of guaicol in diet was administered to 16 male rats (Fisher 344) for 51 weeks. Mild and moderate forestomach hyperplasia was found in 93.8 % of the rats received guaiacol but papilloma and carcinoma were not detected. Forestomach lesions were focal and characterized by down ward basal cell growth. The LOAEL for non-carcinogenic effects is 1000 mg/kg bw/ day, based on calculation regarding forestomach lesions and hyperplasia.

At the dose tested, there was not a treatment related increase in stomach tumor incidence (papilloma and carcinoma) when compared to controls.

Justification for classification or non-classification

Additional information

Two studies were available, but only one, with reliability 2 was selected as a key study. The other one has the reliability 3 and was not taken into account. In this carcinogenicity study (Hirose et al., 1989) according to the OECD guideline 451, 1.5% (corresponding to 1000 mg/kg/day) of gaiacol in diet was administered to 16 male rats (Fisher 344) for 51 weeks. Mild and moderate forestomach hyperplasia was found in 93.8 % of the rats received guaiacol but papilloma and carcinoma were not detected. Forestomach lesions were focal and characterized by down ward basal cell growth.The LOAEL for non-carcinogenic effects is 1000 mg/kg bw/day, based on calculation, regarding forestomach lesions and hyperplasia.

At the dose tested, there was not a treatment related increase in stomach tumor incidence (papilloma and carcinoma) when compared to controls.