Troclosene sodium

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study performed to GLP and guideline

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPP 83-3 (Prenatal Developmental Toxicity Study)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Troclosene sodium

EC Number:

220-767-7

EC Name:

Troclosene sodium

Cas Number:

2893-78-9

Molecular formula:

C3HCl2N3O3.Na

IUPAC Name:

sodium 3,5-dichloro-2,4,6-trioxo-1,3,5-triazinan-1-ide

Details on test material:

- Name of test material (as cited in study report): Sodium cyanurate
- Analytical purity: >99%
- Substance type: powder
- Lot/batch No.: NB: 4,409,462
- Stability under test conditions: Extremely stable with no known expiration date.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton Research Products, Inc. Denver, PA. USA
- Age at study initiation: 6 ½ to 7 months
- Weight at study initiation: 3 to 5 kg
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 28 days


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 61-70
- Humidity (%): 40-60
- Photoperiod: 12 hr light/12 hr dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 1% methyl cellulose in water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
The test material was ground by a mortar and pestle and sieved through a 40 mesh sieve prior to weighing. A specified amount of the test material for each group was then weighed out into a calibrated beaker. A sufficient amount of the vehicle was added and the mixtures were stirred to suspend the test material. An appropriate amount of the vehicle was added to obtain the desired concnetrations. The suspensions were stirred with a magnetic stir bar until homogenous. Dosing solutions were prepared weekly and stored in the refrigerator, Each suspension was stirred for 30 minutes prior to daily dispensing for dosing and continuously during dosing.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

A sample of the vehicle and each dosage suspension was analyzed on the first day of dosing and near the end of the dosing period for verification of dosage concentration.

Details on mating procedure:

- Impregnation procedure: artificial insemination

Duration of treatment / exposure:

days 6-18 post insemination

Frequency of treatment:

daily

Duration of test:

29 days

Doses / concentrations

Remarks:

Doses / Concentrations:
50, 200 and 500 mg/kg bw
Basis:

No. of animals per sex per dose:

20

Control animals:

yes, concurrent vehicle

Examinations

Maternal examinations:

CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations checked: clinical signs of toxicity including physical or behavioural abnormalities. Mortality checks were performed twice daily.



BODY WEIGHT: Yes
- Time schedule for examinations: Gestation day 0, 6, 9, 12, 15, 19, 24 and 29


FOOD CONSUMPTION: Yes
- Time schedule for examinations: Daily during gestation.



POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 29

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes

Fetal examinations:

- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: all per litter
- Skeletal examinations: Yes: all per litter

Statistics:

Statisitcal analyses were perforemd by a Digital Vax 11/730 computer. All analyses were two-tailed with a minimum significance level of 5%. One way analysis of variance followed by Dunnetts test was used to analyze maternal and fetal data inclufing body weights, food consumption, number of viable fetuses, implantation sites and corpora lutea. Mann-Whitney U test was used to compare post-implantation loss, dead fetuses, and resorptions. Fetal sex ratios were analyzed using the Chi-square test. Fishers Exact test was used to analyze the incidence and number of fetal malformations and variations utilizing the dam (litter) as the experimental unit.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Details on maternal toxic effects:
One female at the 500 mg/kg level and two females at the 50 mg/kg group aborted on gestation days 22, 24 and 26 days respectively. No treatment related clinical signs of toxicity or statistically significant difference in body weights were observed during the study. No treatment related gross abnormalities were observed. Slight body weight losses or lack of body weight gains appeared to parallel slightly smaller sizes of litters and reduced proportion of males in litters at 200 and 500 mg/kg bw/d.

Effect levels (maternal animals)

Dose descriptor:

NOEL

Effect level:

50 mg/kg bw/day

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Details on embryotoxic / teratogenic effects:
At the 500 mg/kg level there was a statistically significant increase in post-implantation loss, primarily related to one dam with 7 late resorptions. A statistically significant difference in the foetal sex ratio at the 50 mg/kg level was considered incidental, although non significant reductions occurred at higher dose levels. No treatment related differences were noted in gravid uterus weight, foetal body weight or foetal malformation data

Effect levels (fetuses)

Dose descriptor:

NOEL

Effect level:

500 mg/kg bw/day

Basis for effect level:

other: teratogenicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

No treatment related statistically significant clinical signs of toxicity or difference in body weights were observed during the study. Maternal toxicity (body weight gain, food consumption) was claimed at 200 and 500 mg/kg levels. This was in parallel with a slight reduction in numbers of foetuses/litter and changes in sex ratio of foetuses. There was no evidence of developmental toxicity in the absence of maternal toxicity