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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
fertility, other
Remarks:
Organogenesis
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from NTP

Data source

Reference
Reference Type:
other: Authorized database
Title:
Developmental Toxicity of D-Camphor in Sprague Dawley (CD) Rats
Author:
NTP
Year:
1992
Bibliographic source:
National Toxicology program (NTP), March 1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: as below
Principles of method if other than guideline:
Developmental Toxicity of D-Camphor in Sprague Dawley (CD) Rats
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): D-Camphor
- Molecular formula (if other than submission substance): C10H16O
- Molecular weight (if other than submission substance): 152.2354 g/mole
- Substance type: Organic
Specific details on test material used for the study:
- Name of test material (as cited in study report): D-Camphor
- Molecular formula (if other than submission substance): C10H16O
- Molecular weight (if other than submission substance): 152.2354 g/mole
- Substance type: Organic

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female

Administration / exposure

Route of administration:
oral: gavage
Type of inhalation exposure (if applicable):
not specified
Vehicle:
not specified
Details on mating procedure:
Pregnant female rats were used.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
10 days (gd 6-15).
Frequency of treatment:
Daily
Details on study schedule:
not specified
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day
Dose / conc.:
100 mg/kg bw/day
Dose / conc.:
400 mg/kg bw/day
Dose / conc.:
800 mg/kg bw/day
No. of animals per sex per dose:
not specified
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: Dose was selected based on previous reports indicated that 1250 mg/kg/day CAM causes 90% maternal mortality.
Positive control:
not specified

Examinations

Parental animals: Observations and examinations:
Survival, Clinical sign, Body weight and weight gain, food consumption and water consumption were examined.
Oestrous cyclicity (parental animals):
not specified
Sperm parameters (parental animals):
not specified
Litter observations:
Fetal growth and viability were examined.
Postmortem examinations (parental animals):
Organ weight was examined.
Postmortem examinations (offspring):
External, visceral and skeletal malformations were examined.
Statistics:
not specified
Reproductive indices:
not specified
Offspring viability indices:
not specified

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):
No mortality were observed in treated male and female rats as compared to control.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
Decreased weight gain during the treatment period was observed in treated female rats as compared to control.

Although maternal body weights in all treatment groups were within 5% of control values at all gestational ages, maternal weight gain during the treatment period in the 800 mg/kg/day group was significantly reduced.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
Food consumption was initially suppressed by both 400 and 800 mg/kg/day. But recovered to control levels by the end of the treatment period. No effect on food consumption was seen at 100 mg/kg/day CAM.
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
effects observed, treatment-related
Description (incidence and severity):
Increased maternal water consumption during one or more of the following measurement periods (gd 6 to 9; gd 12 to 15; gd 15 to 18) were observed
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:
no effects observed
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
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
Description (incidence and severity):
No effect on reproductive performance or fetal growth was observed in treated rats as compared to control.

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
800 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
mortality
body weight and weight gain
food consumption and compound intake
organ weights and organ / body weight ratios
reproductive performance
Remarks on result:
other: No effect observed

Target system / organ toxicity (P0)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

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):
No effect on viability of fetus were observed as compared to control.
Body weight and weight changes:
not specified
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:
no effects observed
Description (incidence and severity):
No external abnormality were observed in pups as compared to control.
Histopathological findings:
no effects observed
Description (incidence and severity):
No visceral and skeletal malformations were observed in pups as compared to control.
Other effects:
not specified

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not specified

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
800 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
viability
mortality
gross pathology
histopathology: non-neoplastic
Remarks on result:
other: No effect observed

Target system / organ toxicity (F1)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Overall reproductive toxicity

Reproductive effects observed:
not specified
Treatment related:
not specified
Relation to other toxic effects:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Applicant's summary and conclusion

Conclusions:
NOAEL was considered to be 800 mg/kg bw for P and F1 generation when Sprague Dawley and female rats were treated with D-Camphor orally by gavage for 10 days (gd 6-15).
Executive summary:

In a Developmental Toxicity study, Sprague Dawleyfemale rats were treated withD-Camphorin the concentration of0, 100, 400 and 800 mg/kg bw/dayorally by gavage for10 days (gd 6-15). No mortality were observed in treated dams as compared to control.Decreased weight gain during the treatment period was observed in treated female rats as compared to control. Although maternal body weights in all treatment groups were within 5% of control values at all gestational ages, maternal weight gain during the treatment period in the 800 mg/kg/day group was significantly reduced. Food consumption was initially suppressed at 400 and 800 mg/kg/day. But recovered to control levels by the end of the treatment period. No effect on food consumption was observed at 100 mg/kg/day. Increased maternal water consumption during one or more of the following measurement periods (gd 6 to 9; gd 12 to 15; gd 15 to 18) was observed. Similarly, No effect onreproductive performanceor fetal growth was observed in treated rats as compared to control.Absolute and relative liver weights exhibited a significant dose-related increase, but did not exceed 10% of control values in any individual group. In addition, Noeffect on viability of fetus was observed as compared to control. No external, visceral and skeletal malformations were observed in pups as compared to control. Therefore, NOAEL was considered to be 800 mg/kg bw for P and F1 generation whenSprague Dawleyand female rats were treated withD-Camphororally by gavage for10 days (gd 6-15).