Registration Dossier

Administrative data

Endpoint:
multi-generation reproductive toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
review article or handbook
Title:
Final Report on the Safety Assessment of Pyrogallol
Author:
CIR - COSMETIC INGREDIENT REVIEW
Year:
1991
Bibliographic source:
JOURNAL OF THE AMERICAN COLLEGE OF TOXICOLOGY. 10(1): 67-85

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
- Principle of test:
- Short description of test conditions:
- Parameters analysed / observed:
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
impurity
Test material form:
not specified
Details on test material:
not specified
Specific details on test material used for the study:
no data

Test animals

Species:
rat
Strain:
other: Charles River CD
Sex:
male/female
Details on test animals and environmental conditions:
no data

Administration / exposure

Route of administration:
dermal
Vehicle:
unchanged (no vehicle)
Details on exposure:
The dye was mixed with an equal volume of 6% hydrogen peroxide and applied (0.5 ml) to the skin twice per week throughout mating, gestation, and during the period of lactation to weaning of the F1b, F2b, and F3b litters of the respective generations.
Details on mating procedure:
no data
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
no data
Frequency of treatment:
twice per week
Details on study schedule:
no data
Doses / concentrations
Remarks:
no data available
No. of animals per sex per dose:
A total of 40 males and 40 females were tested
Control animals:
not specified
Details on study design:
no data
Positive control:
no data

Examinations

Parental animals: Observations and examinations:
Fertility, gestation, and viability indices

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
no mortality observed
Description (incidence):
There were no treatment-related changes in general behavior and appearance, body weight, or survival in parents or offspring.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
There were no treatment-related changes in general behavior and appearance, body weight, or survival in parents or offspring.
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:
not specified
Behaviour (functional findings):
no effects observed
Description (incidence and severity):
There were no treatment-related changes in general behavior and appearance, body weight, or survival in parents or offspring.
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
Additionally, there were no treatment-related gross or microscopic lesions observed in F1b parental rats or F3b weaning rats.
Histopathological findings: neoplastic:
no effects observed
Description (incidence and severity):
Additionally, there were no treatment-related gross or microscopic lesions observed in F1b parental rats or F3b weaning rats.
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed

Effect levels (P0)

Key result
Dose descriptor:
NOAEL
Effect level:
0.002 other: mg/animal
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
body weight and weight gain
reproductive performance

Results: P1 (second parental generation)

General toxicity (P1)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
no mortality observed
Description (incidence):
There were no treatment-related changes in general behavior and appearance, body weight, or survival in parents or offspring.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
There were no treatment-related changes in general behavior and appearance, body weight, or survival in parents or offspring.
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:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P1)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed

Effect levels (P1)

Key result
Dose descriptor:
NOAEL
Effect level:
0.002 other: mg/animal
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
body weight and weight gain
reproductive performance

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
no mortality observed
Description (incidence and severity):
There were no treatment-related changes in general behavior and appearance, body weight, or survival in parents or offspring.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
There were no treatment-related changes in general behavior and appearance, body weight, or survival in parents or offspring.
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:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
no effects observed
Description (incidence and severity):
Additionally, there were no treatment-related gross or microscopic lesions observed in F1b parental rats or F3b weaning rats.
Other effects:
not specified

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not specified

Effect levels (F1)

Key result
Dose descriptor:
NOAEL
Generation:
F1b
Effect level:
0.002 other: mg/animal
Based on:
test mat.
Sex:
male/female
Basis for effect level:
mortality
body weight and weight gain

Results: F2 generation

General toxicity (F2)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
no mortality observed
Description (incidence and severity):
There were no treatment-related changes in general behavior and appearance, body weight, or survival in parents or offspring.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
There were no treatment-related changes in general behavior and appearance, body weight, or survival in parents or offspring.
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:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
no effects observed
Description (incidence and severity):
Additionally, there were no treatment-related gross or microscopic lesions observed in F1b parental rats or F3b weaning rats.
Other effects:
not specified

Developmental neurotoxicity (F2)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F2)

Developmental immunotoxicity:
not specified

Effect levels (F2)

Key result
Dose descriptor:
NOAEL
Generation:
F2b
Effect level:
0.002 other: mg/animal
Based on:
test mat.
Sex:
male/female
Basis for effect level:
mortality
body weight and weight gain

Overall reproductive toxicity

Key result
Reproductive effects observed:
no
Treatment related:
no

Any other information on results incl. tables

There were no treatment-related changes in general behavior and appearance, body weight, or survival in parents or offspring.

Mild skin reactions, in treated animals, were noted intermittently throughout the study.

Fertility, gestation, and viability indices were comparable between control and experimental groups.

Additionally, there were no treatment-related gross or microscopic lesions observed in F1b parental rats or F3b weaning rats

Applicant's summary and conclusion

Conclusions:
A multigeneration reproduction study in rats was conducted in males and females dermally exposed to a hair dye formulation that contained 0.4% Pyrogallol.
There were no treatment-related changes in general behavior and appearance, body weight, or survival in parents or offspring. However, mild skin reactions, in treated animals, were noted intermittently throughout the study. Fertility, gestation, and viability indices were comparable between control and experimental groups. Additionally, there were no treatment-related gross or microscopic lesions observed in F1b parental rats or F3b weaning rats.
Executive summary:

A multigeneration reproduction study was conducted using Charles River CD rats.

A total of 40 males and 40 females were tested with a hair dye formulation that contained 0.4% Pyrogallol. The dye was mixed with an equal volume of 6% hydrogen peroxide and applied (0.5 ml) to the skin twice per week throughout mating, gestation, and during the period of lactation to weaning of the F1b, F2b, and F3c, litters of the respective generations. There were no treatment-related changes in general behavior and appearance, body weight, or survival in parents or offspring. However, mild skin reactions, in treated animals, were noted intermittently throughout the study. Fertility, gestation, and viability indices were comparable between control and experimental groups. Additionally, there were no treatment-related gross or microscopic lesions observed in F1b parental rats or F3b weaning rats.