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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Type of information:
other: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No GLP, no guidelines followed, poorly details on test conditions Read across from a similar substance which has the same main component and with a different counter ion that doesn't influence the characteristics related to the specific end-point

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1983
Report date:
1983

Materials and methods

Principles of method if other than guideline:
Malachite Green was administrated to Rabbits by oral gavage. Thalidomide was used as positive
control and untreated animals as untreated control.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Reference substance name:
Malachite Green Oxalate
IUPAC Name:
Malachite Green Oxalate
Details on test material:
- Name of test material: Malachite Green Oxalate
- Source: Dansk Orredforder A/S, Brande, Danmark
- Structure: (C23H25N)2 (COO)2 X 2 (COOH)2
- Analytical purity: > 90% detected by TLC

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
female
Details on test animals or test system and environmental conditions:
ANIMALS TESTED
- Specie: Oryctolagus cuniculus
- Source: commercial laboratory supplier Scott Rabbit Products, Langley, Washington
- Age at study initiation: time-pregnant
- Housing: all animals were housed individually
- Diet: Purina Laboratory Rabbit Chow supplemented by fresh greens
- Water: water ad libitum
CONTROL
- Group: two control group were used: one untreated and one like positive control (treated by
Thalidomide, a known teratogen)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
DIET
- Dose: 5, 10, 20 mg/kg
- Solution: Malachite Green was administrated as an aqueous solution.
- Administration: orally by gavage on days 6 through 18 of gestation
- N. initial animals: 20
POSITIVE CONTROL SOLUTION
- Solution: thalidomide was used as a positive control
- Preparation: Thalidomide was prepared as a suspension in corn oil
- Dose: 150 mg/kg
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
18 days of gestation; orally administration by gavage on days 6 through 18 of gestation
Frequency of treatment:
Frequency of treatment
Daily
Doses / concentrationsopen allclose all
Dose / conc.:
5 mg/kg diet
Dose / conc.:
10 mg/kg diet
Dose / conc.:
20 mg/kg diet
No. of animals per sex per dose:
At dose 5 mg/kg 16 animals; at 10 mg/kg 21; at 20 mg/kg 16.
Control animals:
yes, concurrent vehicle
Details on study design:
PRELIMINARY TEST
Consequently, doses of 2, 50, and 75 mg/kg were selected to determine the maximum dose to be
used with rabbits. Three young, nonpregnant adult New Zealand white rabbits were dosed daily for
13 days in each treatment. Data from this limited study indicated that nonpregnant female rabbits co
uld tolerate 13 consecutive daily doses of 50 mg/kg of Malachite Green. Stanford Research Institute
experience has been that pregnant rabbits are much more sensitive to drugs than nonpregnant ones
so 20 mg/kg was selected as the maximum level to be used in the teratology study.

Examinations

Parental animals: Observations and examinations:
PRELIMINARY TEST
Consequently, doses of 2, 50, and 75 mg/kg were selected to determine the maximum dose to be
used with rabbits. Three young, nonpregnant adult New Zealand white rabbits were dosed daily for
13 days in each treatment. Data from this limited study indicated that nonpregnant female rabbits co
uld tolerate 13 consecutive daily doses of 50 mg/kg of Malachite Green. Stanford Research Institute
experience has been that pregnant rabbits are much more sensitive to drugs than nonpregnant ones
so 20 mg/kg was selected as the maximum level to be used in the teratology study.
OTHER:
Young were thoroughly examined at delivery, weighed and incubated for 24 hours. During incubation
they were observed hourly for viability during the first 4 hours and again at 24 hours
Litter observations:
yes
Postmortem examinations (parental animals):
yes
Postmortem examinations (offspring):
yes

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Treated adult animals were consistently lower in average total body weight than the untreated controls
at the end of the study, but there were no overt signs of toxicity
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related

Effect levels (P0)

Dose descriptor:
NOEL
Effect level:
< 5 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
clinical signs
body weight and weight gain
reproductive performance

Results: F1 generation

Effect levels (F1)

Dose descriptor:
NOEL
Generation:
F1
Effect level:
< 5 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
viability
clinical signs
other: scheletal malformations

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

At all

three doses there were significant increases in preimplantation losses, primarily due to early resorption of fetuses

and decreases in the number of living fetuses.

Applicant's summary and conclusion

Conclusions:
At all
three doses there were significant increases in preimplantation losses, primarily due to early resorption of fetuses
and decreases in the number of living fetuses.