Registration Dossier

Administrative data

Description of key information

Data are available for the oral and dermal route.

Only reliability 4 type of information are available for the oral route.

In the dermal route repeated dose toxicity studies, significant adverse effects were seen only at local level (skin, at the Site of Administration).

Key value for chemical safety assessment

Toxic effect type:
dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
abstract
Qualifier:
no guideline available
Principles of method if other than guideline:
- Principle of test: a repeated dose test was performed to rabbit
- Short description of test conditions: no data
- Parameters analysed / observed: mortality and effects related to administration of the substance
GLP compliance:
not specified
Specific details on test material used for the study:
no data
Species:
rabbit
Strain:
not specified
Details on species / strain selection:
no data
Sex:
not specified
Details on test animals and environmental conditions:
no data
Route of administration:
oral: gavage
Details on route of administration:
no data
Vehicle:
not specified
Details on oral exposure:
no data
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
10-day exposure
Frequency of treatment:
no data
Dose / conc.:
500 mg/kg bw/day (nominal)
Dose / conc.:
1 000 mg/kg bw/day (nominal)
No. of animals per sex per dose:
total of animals tested: 6
Sex: n.p.
Control animals:
not specified
Details on study design:
observation period n.p.
Positive control:
no data
Key result
Dose descriptor:
other: repeated-dose LD50
Effect level:
700 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
mortality

A repeated-dose LD50 of 700 mg/kg/day was determined. The following symptoms were observed in some treated rabbits: congestion of the lung; congestion of the liver, with prominent lobules (alternate light and congested areas were observed); congestion and swelling of the kidneys; congestion and enlargement of the spleen; and gastritis, usually with hemorrhages and/or ulcers. A smooth white exudate was induced on the gastric mucosa and there was a varying degree of enteritis in the duodenum and cecum. The doses which caused these effects and the number of animals affected were n.p.

Conclusions:
In rabbits, a multiple oral dose (LD50) of pyrogallol is 0.7 g/kg per day when administered daily for ten days.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Qualifier:
no guideline available
Principles of method if other than guideline:
- Principle of test:
Based on the subchronic studies, the doses for the 2-year studies in rats and mice were 5, 20 and 75 mg/kg of pyrogallol. The study were conducted in both sexes of F344/N rats mice.
- Short description of test conditions: Groups of 50 male and 50 female rats and mice received dermal applications of pyrogallol in 95% ethanol at doses of 5, 20, or 75 mg/kg, or ethanol vehicle control alone, 5 days per week for up to 104 (rats) or 105 (mice) weeks. Body weights were recorded weekly for 13 weeks and monthly thereafter.
- Parameters analysed / observed: The incidences of microscopic non-neoplastic lesions at the site of application were observed.
GLP compliance:
yes
Remarks:
These studies were conducted in compliance with FDA Good Laboratory Practice for nonclinical laboratory studies (21 CFR 58).
Limit test:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Pyrogallol was obtained from Aceto Corporation (Lake Success, NY; lot number 010326).
- Expiration date of the lot/batch: not specified
- Purity test date: Purity was determined by high-performance liquid chromatography with ultraviolet detection to be greater than 99%.

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: not specified
- Stability under test conditions: not specified
- Solubility and stability of the test substance in the solvent/vehicle: not specified
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: not specified

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: not specified
- Preliminary purification step (if any): not specified
- Final dilution of a dissolved solid, stock liquid or gel: not specified
- Final preparation of a solid: not specified

OTHER SPECIFICS: Dose formulations were prepared by mixing pyrogallol and95% ethanol to give the required concentrations. Dose formulations were analyzed three times during the subchronic study and every three months during the chronic study and were within 10% of target pyrogallol concentrations.
Species:
rat
Strain:
Fischer 344
Remarks:
F344/N
Details on species / strain selection:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: obtained from Taconic Farms, Inc. (Germantown, NY)
- Females (if applicable) nulliparous and non-pregnant: [yes/no] not specified
- Age at study initiation: rats were 6–8 weeks old
- Weight at study initiation: not specified
- Fasting period before study: not specified
- Housing: housed individually
- Diet (e.g. ad libitum): Irradiated NTP-2000 wafer feed (Zeigler Brothers, Inc., Gardners, PA) was available ad libitum.
- Water (e.g. ad libitum): tap water (Columbus, OH, municipal supply) was available ad libitum.
- Acclimation period: quarantined for 11 days

DETAILS OF FOOD AND WATER QUALITY: see above

ENVIRONMENTAL CONDITIONS
- Temperature (°C): not specified
- Humidity (%): not specified
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): not specified

IN-LIFE DATES: From: To: not specified

Animal care and use were in accordance with the Laboratory Animal Welfare Act of 1966 (P.L. 89–544) as amended and the Public Health Service Policy on Humane Care and Use of Animals. Animals were treated humanely and with regard for alleviation of pain and distress. All animals were housed in facilities accredited by the Association for Assessment and Accreditation of Laboratory Animal Care and all procedures were approved by Battelle's Institutional Animal Care and Use Committee.
Type of coverage:
other: to naïve skin
Vehicle:
ethanol
Details on exposure:
TEST SITE
- Area of exposure: Pyrogallol was administered over the application site with a Corning Lambda (Corning, Inc., Corning, NY) single channel pipetter with a disposable polyethylene tip
- % coverage: not specified
- Type of wrap if used:
- Time intervals for shavings or clipplings: An area slightly larger than the interscapular application site was clipped 24 hours before the first dose and weekly thereafter.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not specified
- Time after start of exposure: not specified

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Dosing volumes were 0.5 mL/kg body weight
- Concentration (if solution):
- Constant volume or concentration used: yes
- For solids, paste formed: not applicable

VEHICLE
- Justification for use and choice of vehicle (if other than water): not specified
- Amount(s) applied (volume or weight with unit): not specified
- Concentration (if solution): 95%
- Lot/batch no. (if required): not specified
- Purity: not specified

USE OF RESTRAINERS FOR PREVENTING INGESTION: not specified
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
not applicable
Duration of treatment / exposure:
two -year study
Frequency of treatment:
5 days per week for 104 weeks
Dose / conc.:
5 mg/kg bw/day
Remarks:
pyrogallol in 95% ethanol
Dose / conc.:
20 mg/kg bw/day
Remarks:
pyrogallol in 95% ethanol
Dose / conc.:
75 mg/kg bw/day
Remarks:
pyrogallol in 95% ethanol
No. of animals per sex per dose:
Groups of 50 male and 50 female rats
Control animals:
yes, concurrent vehicle
Positive control:
no
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: no
- Time schedule: not applicable
- Cage side observations checked in table [No.?] were included. not applicable

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: clinical signs were recorded weekly

DERMAL IRRITATION (if dermal study): no
- Time schedule for examinations: not applicable

BODY WEIGHT: Yes
- Time schedule for examinations: recorded weekly.

FOOD CONSUMPTION: no
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: not applicable

FOOD EFFICIENCY: no
- 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: not applicable

WATER CONSUMPTION: no
- Time schedule for examinations: not applicable

OPHTHALMOSCOPIC EXAMINATION: no
- Time schedule for examinations: not applicable
- Dose groups that were examined: not applicable

HAEMATOLOGY: no
- Time schedule for collection of blood: not applicable
- Anaesthetic used for blood collection: not applicable
- Animals fasted: not applicable
- How many animals: not applicable
- Parameters checked in table [No.?] were examined. not applicable

CLINICAL CHEMISTRY: no
- Time schedule for collection of blood: not applicable
- Animals fasted: not applicable
- How many animals: not applicable
- Parameters checked in table [No.?] were examined. not applicable

URINALYSIS: no
- Time schedule for collection of urine: not applicable
- Metabolism cages used for collection of urine: not applicable
- Animals fasted: not applicable
- Parameters checked in table [No.?] were examined. not applicable

NEUROBEHAVIOURAL EXAMINATION: No
- Time schedule for examinations: not applicable
- Dose groups that were examined: not applicable
- Battery of functions tested: sensory activity / grip strength / motor activity / other: not applicable

OTHER: Weights of major organs were recorded at necropsy, including heart, liver, kidney, lung, testis, uterus, thymus and thyroid gland.

Animals were observed twice daily and clinical findings were recorded monthly beginning at week 5.
Sacrifice and pathology:
GROSS PATHOLOGY: Not specified

HISTOPATHOLOGY: Yes
Other examinations:
no other examinations were performed.
Statistics:
To determine statistical differences between incidences, Fisher exact test and poly-3 test were used where applicable. Organ and body weight data were analyzed with the parametric multiple comparison procedures of Dunnett and Williams. Analysis of effects on survival used Cox's [25] method for testing two groups for equality and Tarone's life table test to identify dose-related trends.
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Irritation and/or ulceration of the skin at the site of application were the only chemical-related clinical findings and occurred predominantly in the 20 and 75 mg/kg male and female groups.
Dermal irritation:
effects observed, treatment-related
Description (incidence and severity):
Lesions at the SOA were morphologically similar to those observed in the 3-month study. The incidences of hyperplasia and hyperkeratosis were significantly greater than those in the vehicle control groups in most dosed groups; incidences of inflammation were significantly increased in several groups treated with 20 or 75 mg/kg. In addition to lesions already seen in the 3-months study, sebaceous gland hyperplasia was significantly increased.
Mortality:
mortality observed, treatment-related
Description (incidence):
Survival of 75 mg/kg female mice was significantly decreased, as 23 female mice were euthanized before study end due to the presence of ulcers at the SOA.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
Mean body weights of dosed groups of male and female rats and male mice were similar to that of the vehicle control groups. I
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
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
There were no significant changes in the absolute or relative organ weights at necropsy.
Gross pathological findings:
not examined
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Squamous papilloma occurs as an exophytic growth composed of an inner connective tissue core with branching fronds covered by an outer layer of hyperplastic squamous epithelium in male rat exposed to 75 mg/kg Pyrogallol for 2 years.
Histopathological findings: neoplastic:
not examined
Other effects:
not examined
Dose descriptor:
LOAEL
Effect level:
5 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
dermal irritation
body weight and weight gain
histopathology: non-neoplastic
Dose descriptor:
NOAEL
Remarks on result:
not determinable
Remarks:
the adverse toxic effect was observed at the first lowest dose
Critical effects observed:
yes
Lowest effective dose / conc.:
5 mg/kg bw/day
System:
other: Squamous hyperplasia, Hyperkeratosis, Chronic active inflammation, Ulcer
Organ:
skin
Treatment related:
yes
Dose response relationship:
not specified
Relevant for humans:
not specified
Conclusions:
Skin at the SOA was the primary site of toxicity for pyrogallol for this 3-months study. In conclusion, dermal administration of pyrogallol caused high incidences of nonneoplastic lesions of the skin at the SOA in male and female rats at doses as low as 5 mg/kg/ day. These studies provide the first comprehensive assessment of pyrogallol toxicity in mammals and can be used to assess possible risks to humans from dermal pyrogallol exposure
Executive summary:

Pyrogallol (CAS No. 87-66-1), a benzenetriol used historically as a hair dye and currently in a number of industrial applications, was nominated to the National Toxicology Program (NTP) for testing based on lack of toxicity and carcinogenicity data. Three-month and two-year toxicity studies to determine the toxicity and carcinogenicity of pyrogallol when applied to naïve skin (i.e. dermal administration) were conducted in both sexes of F344/N rats and B6C3F1/N mice. In the three-month studies, adult rodents were administered pyrogallol in 95% ethanol 5 days per week for 3 months at doses of up to 150 mg /kg body weight (rats) or 600 mg/kg (mice). Based on the subchronic studies, the doses for the 2-year studies in rats and mice were 5, 20 and 75 mg/kg of pyrogallol. All mice and most rats survived until the end of the three-month study and body weights were comparable to controls. During the 2-year study, survival of dosed rats and male

mice was comparable to controls; however survival of 75 mg/kg female mice was significantly decreased compared to controls. The incidences of microscopic non-neoplastic lesions at the site of application were significantly higher in all dosed groups of rats and mice and in both the 3 months and 2-year studies. In the 2-year study, hyperplasia, hyperkeratosis and inflammation tended to be more severe in mice than in rats, and in the mice they tended to be more severe in females than in males. The incidence of squamous cell carcinoma at the site of application (SOA) in 75 mg/kg female mice and SOA squamous cell papillomas in 75 mg/kg male mice were greater than controls. Pyrogallol was carcinogenic in female mice and may have caused tumors in male mice.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LOAEL
5 mg/kg bw/day
Study duration:
chronic
Species:
rat
System:
other: SKIN

Repeated dose toxicity: dermal - local effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Qualifier:
no guideline available
Principles of method if other than guideline:
- Principle of test:
Based on the subchronic studies, the doses for the 2-year studies in rats and mice were 5, 20 and 75 mg/kg of pyrogallol. The study were conducted in both sexes of F344/N rats mice.
- Short description of test conditions: Groups of 50 male and 50 female rats and mice received dermal applications of pyrogallol in 95% ethanol at doses of 5, 20, or 75 mg/kg, or ethanol vehicle control alone, 5 days per week for up to 104 (rats) or 105 (mice) weeks. Body weights were recorded weekly for 13 weeks and monthly thereafter.
- Parameters analysed / observed: The incidences of microscopic non-neoplastic lesions at the site of application were observed.
GLP compliance:
yes
Remarks:
These studies were conducted in compliance with FDA Good Laboratory Practice for nonclinical laboratory studies (21 CFR 58).
Limit test:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Pyrogallol was obtained from Aceto Corporation (Lake Success, NY; lot number 010326).
- Expiration date of the lot/batch: not specified
- Purity test date: Purity was determined by high-performance liquid chromatography with ultraviolet detection to be greater than 99%.

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: not specified
- Stability under test conditions: not specified
- Solubility and stability of the test substance in the solvent/vehicle: not specified
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: not specified

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: not specified
- Preliminary purification step (if any): not specified
- Final dilution of a dissolved solid, stock liquid or gel: not specified
- Final preparation of a solid: not specified

OTHER SPECIFICS: Dose formulations were prepared by mixing pyrogallol and95% ethanol to give the required concentrations. Dose formulations were analyzed three times during the subchronic study and every three months during the chronic study and were within 10% of target pyrogallol concentrations.
Species:
rat
Strain:
Fischer 344
Remarks:
F344/N
Details on species / strain selection:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: obtained from Taconic Farms, Inc. (Germantown, NY)
- Females (if applicable) nulliparous and non-pregnant: [yes/no] not specified
- Age at study initiation: rats were 6–8 weeks old
- Weight at study initiation: not specified
- Fasting period before study: not specified
- Housing: housed individually
- Diet (e.g. ad libitum): Irradiated NTP-2000 wafer feed (Zeigler Brothers, Inc., Gardners, PA) was available ad libitum.
- Water (e.g. ad libitum): tap water (Columbus, OH, municipal supply) was available ad libitum.
- Acclimation period: quarantined for 11 days

DETAILS OF FOOD AND WATER QUALITY: see above

ENVIRONMENTAL CONDITIONS
- Temperature (°C): not specified
- Humidity (%): not specified
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): not specified

IN-LIFE DATES: From: To: not specified

Animal care and use were in accordance with the Laboratory Animal Welfare Act of 1966 (P.L. 89–544) as amended and the Public Health Service Policy on Humane Care and Use of Animals. Animals were treated humanely and with regard for alleviation of pain and distress. All animals were housed in facilities accredited by the Association for Assessment and Accreditation of Laboratory Animal Care and all procedures were approved by Battelle's Institutional Animal Care and Use Committee.
Type of coverage:
other: to naïve skin
Vehicle:
ethanol
Details on exposure:
TEST SITE
- Area of exposure: Pyrogallol was administered over the application site with a Corning Lambda (Corning, Inc., Corning, NY) single channel pipetter with a disposable polyethylene tip
- % coverage: not specified
- Type of wrap if used:
- Time intervals for shavings or clipplings: An area slightly larger than the interscapular application site was clipped 24 hours before the first dose and weekly thereafter.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not specified
- Time after start of exposure: not specified

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Dosing volumes were 0.5 mL/kg body weight
- Concentration (if solution):
- Constant volume or concentration used: yes
- For solids, paste formed: not applicable

VEHICLE
- Justification for use and choice of vehicle (if other than water): not specified
- Amount(s) applied (volume or weight with unit): not specified
- Concentration (if solution): 95%
- Lot/batch no. (if required): not specified
- Purity: not specified

USE OF RESTRAINERS FOR PREVENTING INGESTION: not specified
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
not applicable
Duration of treatment / exposure:
two -year study
Frequency of treatment:
5 days per week for 104 weeks
Dose / conc.:
5 mg/kg bw/day
Remarks:
pyrogallol in 95% ethanol
Dose / conc.:
20 mg/kg bw/day
Remarks:
pyrogallol in 95% ethanol
Dose / conc.:
75 mg/kg bw/day
Remarks:
pyrogallol in 95% ethanol
No. of animals per sex per dose:
Groups of 50 male and 50 female rats
Control animals:
yes, concurrent vehicle
Positive control:
no
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: no
- Time schedule: not applicable
- Cage side observations checked in table [No.?] were included. not applicable

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: clinical signs were recorded weekly

DERMAL IRRITATION (if dermal study): no
- Time schedule for examinations: not applicable

BODY WEIGHT: Yes
- Time schedule for examinations: recorded weekly.

FOOD CONSUMPTION: no
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: not applicable

FOOD EFFICIENCY: no
- 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: not applicable

WATER CONSUMPTION: no
- Time schedule for examinations: not applicable

OPHTHALMOSCOPIC EXAMINATION: no
- Time schedule for examinations: not applicable
- Dose groups that were examined: not applicable

HAEMATOLOGY: no
- Time schedule for collection of blood: not applicable
- Anaesthetic used for blood collection: not applicable
- Animals fasted: not applicable
- How many animals: not applicable
- Parameters checked in table [No.?] were examined. not applicable

CLINICAL CHEMISTRY: no
- Time schedule for collection of blood: not applicable
- Animals fasted: not applicable
- How many animals: not applicable
- Parameters checked in table [No.?] were examined. not applicable

URINALYSIS: no
- Time schedule for collection of urine: not applicable
- Metabolism cages used for collection of urine: not applicable
- Animals fasted: not applicable
- Parameters checked in table [No.?] were examined. not applicable

NEUROBEHAVIOURAL EXAMINATION: No
- Time schedule for examinations: not applicable
- Dose groups that were examined: not applicable
- Battery of functions tested: sensory activity / grip strength / motor activity / other: not applicable

OTHER: Weights of major organs were recorded at necropsy, including heart, liver, kidney, lung, testis, uterus, thymus and thyroid gland.

Animals were observed twice daily and clinical findings were recorded monthly beginning at week 5.
Sacrifice and pathology:
GROSS PATHOLOGY: Not specified

HISTOPATHOLOGY: Yes
Other examinations:
no other examinations were performed.
Statistics:
To determine statistical differences between incidences, Fisher exact test and poly-3 test were used where applicable. Organ and body weight data were analyzed with the parametric multiple comparison procedures of Dunnett and Williams. Analysis of effects on survival used Cox's [25] method for testing two groups for equality and Tarone's life table test to identify dose-related trends.
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Irritation and/or ulceration of the skin at the site of application were the only chemical-related clinical findings and occurred predominantly in the 20 and 75 mg/kg male and female groups.
Dermal irritation:
effects observed, treatment-related
Description (incidence and severity):
Lesions at the SOA were morphologically similar to those observed in the 3-month study. The incidences of hyperplasia and hyperkeratosis were significantly greater than those in the vehicle control groups in most dosed groups; incidences of inflammation were significantly increased in several groups treated with 20 or 75 mg/kg. In addition to lesions already seen in the 3-months study, sebaceous gland hyperplasia was significantly increased.
Mortality:
mortality observed, treatment-related
Description (incidence):
Survival of 75 mg/kg female mice was significantly decreased, as 23 female mice were euthanized before study end due to the presence of ulcers at the SOA.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
Mean body weights of dosed groups of male and female rats and male mice were similar to that of the vehicle control groups. I
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
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
There were no significant changes in the absolute or relative organ weights at necropsy.
Gross pathological findings:
not examined
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Squamous papilloma occurs as an exophytic growth composed of an inner connective tissue core with branching fronds covered by an outer layer of hyperplastic squamous epithelium in male rat exposed to 75 mg/kg Pyrogallol for 2 years.
Histopathological findings: neoplastic:
not examined
Other effects:
not examined
Dose descriptor:
LOAEL
Effect level:
5 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
dermal irritation
body weight and weight gain
histopathology: non-neoplastic
Dose descriptor:
NOAEL
Remarks on result:
not determinable
Remarks:
the adverse toxic effect was observed at the first lowest dose
Critical effects observed:
yes
Lowest effective dose / conc.:
5 mg/kg bw/day
System:
other: Squamous hyperplasia, Hyperkeratosis, Chronic active inflammation, Ulcer
Organ:
skin
Treatment related:
yes
Dose response relationship:
not specified
Relevant for humans:
not specified
Conclusions:
Skin at the SOA was the primary site of toxicity for pyrogallol for this 3-months study. In conclusion, dermal administration of pyrogallol caused high incidences of nonneoplastic lesions of the skin at the SOA in male and female rats at doses as low as 5 mg/kg/ day. These studies provide the first comprehensive assessment of pyrogallol toxicity in mammals and can be used to assess possible risks to humans from dermal pyrogallol exposure
Executive summary:

Pyrogallol (CAS No. 87-66-1), a benzenetriol used historically as a hair dye and currently in a number of industrial applications, was nominated to the National Toxicology Program (NTP) for testing based on lack of toxicity and carcinogenicity data. Three-month and two-year toxicity studies to determine the toxicity and carcinogenicity of pyrogallol when applied to naïve skin (i.e. dermal administration) were conducted in both sexes of F344/N rats and B6C3F1/N mice. In the three-month studies, adult rodents were administered pyrogallol in 95% ethanol 5 days per week for 3 months at doses of up to 150 mg /kg body weight (rats) or 600 mg/kg (mice). Based on the subchronic studies, the doses for the 2-year studies in rats and mice were 5, 20 and 75 mg/kg of pyrogallol. All mice and most rats survived until the end of the three-month study and body weights were comparable to controls. During the 2-year study, survival of dosed rats and male

mice was comparable to controls; however survival of 75 mg/kg female mice was significantly decreased compared to controls. The incidences of microscopic non-neoplastic lesions at the site of application were significantly higher in all dosed groups of rats and mice and in both the 3 months and 2-year studies. In the 2-year study, hyperplasia, hyperkeratosis and inflammation tended to be more severe in mice than in rats, and in the mice they tended to be more severe in females than in males. The incidence of squamous cell carcinoma at the site of application (SOA) in 75 mg/kg female mice and SOA squamous cell papillomas in 75 mg/kg male mice were greater than controls. Pyrogallol was carcinogenic in female mice and may have caused tumors in male mice.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
BMDL10
31 µg/cm²
Study duration:
chronic
Species:
rat

Additional information

Justification for classification or non-classification

Based on the available data, the substance does not show a toxicity to a specific target organ (toxicity is local, on skin, at the site of application).

No classification is required.