1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)pyridin-2(1H)-one, compound with 2-aminoethanol (1:1)

Toxicity to reproduction: other studies

Administrative data

Endpoint:

toxicity to reproduction: other studies

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was conducted prior to established GLP principles and existing OECD test guidelines but was performed according to accepted scientific standards. The study is well conducted and documented. It is acceptable for evaluation purposes.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Peri- / Postnatal Developmental Study (Reproductive Toxicity Segment III Study). Administration of test compound during the last stage of gestation and the period of lactation to evaluate the effects on neonatal growth.

GLP compliance:

no

Type of method:

in vivo

Test material

Test material information

Constituent 1

Reference substance name:

Octopirox

IUPAC Name:

Octopirox

Constituent 2

Reference substance name:

piroctone olamine

IUPAC Name:

piroctone olamine

Constituent 3

Reference substance name:

1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)pyridin-2(1H)-one, compound with 2-aminoethanol (1:1)

EC Number:

272-574-2

EC Name:

1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)pyridin-2(1H)-one, compound with 2-aminoethanol (1:1)

Cas Number:

68890-66-4

Molecular formula:

C14H23NO2.C2H7NO

IUPAC Name:

1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)pyridin-2(1H)-one, compound with 2-aminoethanol (1:1)

Constituent 4

Reference substance name:

1-Hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2-pyridone, 2-aminoethanol salt

IUPAC Name:

1-Hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2-pyridone, 2-aminoethanol salt

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CLEA Japan, Inc.
- Age at study initiation: 10 - 12 weeks
- Weight at study initiation: approximately 185 g
- Fasting period before study: no
- Housing: individual
- Use of restrainers for preventing ingestion (if dermal): no
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2 °C
- Humidity (%): 55 +/- 5 %
- Air changes (per hr): 12 times per hour
- Photoperiod (hrs dark / hrs light): 12 hour interval

Administration / exposure

Route of administration:

subcutaneous

Vehicle:

CMC (carboxymethyl cellulose)

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
Daily preparation of suspensions in 0.5 % CMC at appropriate concentrations

VEHICLE
- Justification for use and choice of vehicle (if other than water): CMC is a recommended and accepted vehicle

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

During last third of gestation and the perio of lactation

Frequency of treatment:

once per day

Duration of test:

until 21st day after delivery

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0 mg/kg bw
Basis:
nominal conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
20 mg/kg bw
Basis:
nominal conc.

Doses / concentrations 3

Remarks:

Doses / Concentrations:
100 mg/kg bw
Basis:
nominal conc.

Doses / concentrations 4

Remarks:

Doses / Concentrations:
500 mg/kg bw
Basis:
nominal conc.

No. of animals per sex per dose:

22 females (control group), 23 females (low dose group), 24 females (mid dose group), 24 females (high dose group)

Control animals:

yes, concurrent vehicle

Details on study design:

Daily subcutaneous administration of Piroctone olamine to female rats during gestation and the period of lactation (gestation day 17 up to 21st day
after delivery)

Statistics:

yes

Results and discussion

Effect levels

1

Dose descriptor:

NOEL

Effect level:

>= 500 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: peri- / postnatal development of offspring, overall effects, reproductive parameters

2

Dose descriptor:

NOAEL

Effect level:

>= 500 mg/kg bw/day (nominal)

Sex:

female

Basis for effect level:

other: overall effects of dams

Observed effects

no changes attributable to treatment observed

Applicant's summary and conclusion

Conclusions:

Piroctone olamine has no effects on the peri- / postnatal development in rats

Executive summary:

Piroctone was subcutaneously administered daily to female rats at daily doses of 0, 20, 100 or 500 mg/kg body weight during the last third of gestation and the period of lactation (from day 17 of gestation until day 21 after delivery) to investigate potential effects on the growth of neonatals. Body weight gain of the dams of the highest dose-group was slightly but statistically not significantly depressed. No effects on body weights were observed during lactation. Food consumption decreased in each treatment-group at the end of pregnancy, but no changes were observed during lactation. No changes attributable to treatment occurred in the weights of organs examined (heart, lung, liver, kidneys, adrenals). Regarding the offspring, no treatment related abnormalities were noticed in the following at birth and during postnatal development: various parameters at birth, general differentiation, functions, open field behaviour and learning ability. Postnatal development (opening of ear auricles, emergence of abdominal hair, eruption of upper incisors, opening of eyelids, descent of testis, opening of vagina). No changes attributable to the treatment were observed in the skeletons. Examinations of the F1 offspring for their fertility revealed no abnormalities. Various maternal and fetal parameters examined at cesarean section were unaffected. In summary, subcutaneous administration of Piroctone olamine during the last third of gestation including the period of lactation had no significant influence on the peri- / postnatal development in rats.