p-phenylenediamine

Toxicity to reproduction

Administrative data

Endpoint:

multi-generation reproductive toxicity

Remarks:

based on test type (migrated information)

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was performed using oxidative hair dye containing 2, 3, or 4% test substance.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1988

Materials and methods

Principles of method if other than guideline:

Samples were applied topically twice weekly throughout the growth, mating, gestation and lactation phases of the F0 parents to the weaning of the F1a and F2b litters. Fertility, gestation and foetal viability indices and body weights were evaluated for the six treatment groups and these were compared with the values for the three concurrent control groups. After the F2b litters had been weaned, five male and five female F1 parents were necropsied and tissues were taken for microscopic examination.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Details on test material:

- Purity: The dye used to prepare the formulations was obtained from commercial suppliers and was used without further purification. All materials were within the Clairol specifications for use in the manufacture of hair-colouring products.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

dermal

Vehicle:

other: The test substance was mixed in a formulation with many other components in three different concentrations. The test formulations were then prepared fresh for each application by mixing equal volumes of the dye solution and 6% hydrogen peroxide.

Details on mating procedure:

F0 and F1 males and females were paired, care being taken to ensure that littermates were not paired. Mating continued for 15 days during which time the females were examined daily for the presence of a sperm plug in the vagina. The day on which sperm or the copulatory plug was found was termed day 0 of gestation. After weaning of the F1a and F2a litters, the rats were given a 10-day rest and were re-mated to produce the F1b and F2b litters, respectively.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Parental rats (P1 and F1 generation) were dosed daily for 100 days prior to cohabitation, during the cohabitation period (mating), during gestation, and during lactation, until the weaning of the offspring.

Frequency of treatment:

twice weekly

Details on study schedule:

- F1 parental animals not mated until 100 days after selected from the F1 litters.
- Selection of parents from F1 generation once pups were weaned (no age mentioned).

Doses / concentrations

Remarks:

Doses / Concentrations:
2.0, 3.0, 4.0% in oxidative hair dye
Basis:

No. of animals per sex per dose:

F0: 40/sex/dose
F1: 20/ sex/dose

Control animals:

yes, concurrent no treatment

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

Dose descriptor:

other: reproductive effects

Effect level:

> 4 other: % test substance in oxidative hair dye

Sex:

male/female

Basis for effect level:

other: No effect on reproductive performance or on health and survival of developing foetus and postnatal animal.

Remarks on result:

other: Generation: F1a, F1b, F2a, F2b (migrated information)

Overall reproductive toxicity

Reproductive effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Based on the results of these studies, the frequent topical application of oxidative hair dyes does not appear to have an adverse effect on reproductive performance or on the health and survival of the developing foetus and postnatal animal.

Executive summary:

A two-generation reproduction study was conducted in Sprague-Dawley rats receiving topical applications of oxidative hair-colouring formulations. These formulations were prepared as prototypes of permanent hair colourings using the base ingredients and primary intermediates and couplers most often used in this kind of product. Among the dyes included in the various formulations was the test substance at 2.0, 3.0, or 4.0%. The dye solutions were mixed with an equal volume of 6% hydrogen peroxide prior to application. In the reproduction study the samples were applied topically twice weekly throughout the growth, mating, gestation and lactation phases of the F₀ parents to the weaning of the F_1a and F_2b litters. Fertility, gestation and foetal viability indices and body weights were evaluated and these were compared with the values for the three concurrent control groups. In the reproduction phase the application of hair dyes had no adverse effect on the fertility of the males or females, or on gestation, lactation and weaning indices. The average number weaned per litter and the mean body weights of the weanlings were comparable among the treated and control groups. On the basis of the results of the studies reported here the authors conclude that the frequent topical application of oxidative hair dyes containing the test substance and other commonly used intermediates and couplers has no adverse effects on reproduction.