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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
one-generation reproductive toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
Data is from secondary source

Data source

Reference
Reference Type:
secondary source
Title:
SIDS Initial Assessment Profiles agreed in the course of the OECD HPV Chemicals Programme from 1993 to 2011; OECD Environment, Health and Safety Publications; Series on Testing & Assessment No. 166.
Author:
Organization for Economic Co-operation and Development, Feb 27th, 2012.
Year:
2012
Bibliographic source:
Environment Directorate Joint Meeting of the chemicals committee and the working party on chemicals, pesticides and biotechnology, ENV/JM/MONO(2012)4/Part6.

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
Principles of method if other than guideline:
Repeated dose oral toxicity study with the reproduction / developmental toxicity screening test (OECD TG 422) of 4-methoxybenzaldehyde; Anisaldehyde in rats
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Liquid
Details on test material:
- Name of test material (as cited in study report): p-methoxybenzaldehyde
- Molecular formula : C8H8O2
- Molecular weight : 136.149 g/mol
- Substance type: Organic
- Physical state: liquid
Specific details on test material used for the study:
- Name of test material (as cited in study report): p-methoxybenzaldehyde
- Molecular formula : C8H8O2
- Molecular weight : 136.149 g/mol
- Substance type: Organic
- Physical state: liquid

Test animals

Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No data available
- Age at study initiation: No data available
- Weight at study initiation: No data available
- Fasting period before study: No data available
- Housing: No data available
- Diet (e.g. ad libitum): No data available
- Water (e.g. ad libitum): No data available
- Acclimation period: No data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available
- Humidity (%):No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available

IN-LIFE DATES: From: To: No data available

Administration / exposure

Route of administration:
oral: gavage
Type of inhalation exposure (if applicable):
not specified
Vehicle:
not specified
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: No data available

DIET PREPARATION
- Rate of preparation of diet (frequency): No data available
- Mixing appropriate amounts with (Type of food): No data available
- Storage temperature of food: No data available

VEHICLE
- Justification for use and choice of vehicle (if other than water): No data available
- Concentration in vehicle: No data available
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available
Details on mating procedure:
No data available
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data available
Duration of treatment / exposure:
Duration of exposure:
For males: Male rats were dosed for 42 days from 14 days before mating.
For females: Female rats were dosed from 14 days before mating to day 4 of lactation throughout the mating and pregnancy period.
Frequency of treatment:
Daily for 42 days
Details on study schedule:
No data available
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day
Dose / conc.:
20 mg/kg bw/day
Dose / conc.:
100 mg/kg bw/day
Dose / conc.:
500 mg/kg bw/day
No. of animals per sex per dose:
No data available
Control animals:
yes, concurrent vehicle
Details on study design:
No data available
Positive control:
No data available

Examinations

Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: No data available
- Cage side observations checked in table [No.?] were included. Mortality was noted

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: morphological appearance of pups was examined

BODY WEIGHT: No data available
- Time schedule for examinations:

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data available
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes / No / No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data available
- Time schedule for examinations:

OTHER:
Organ weight: yes
Oestrous cyclicity (parental animals):
Yes, estrous cycle and number of corpora lutea
Sperm parameters (parental animals):
Epididymis weight was measured
Postmortem examinations (parental animals):
SACRIFICE
- Male animals: All surviving animals [describe when, e.g. as soon as possible after the last litters in each generation were produced.] No data available
- Maternal animals: All surviving animals [describe when, e.g. after the last litter of each generation was weaned.] No data available

GROSS NECROPSY
- Gross necropsy consisted of [external and internal examinations including the cervical, thoracic, and abdominal viscera.] No data available

HISTOPATHOLOGY / ORGAN WEIGHTS Yes
Reproductive organs
Postmortem examinations (offspring):
No data available
Statistics:
No data available
Reproductive indices:
Fertility index and delivery index was noted
Offspring viability indices:
The number of pups and the number of live pups on lactation day 0 and 4 was noted

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
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
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
no effects observed
Description (incidence and severity):
The compound showed no adverse effects in terms of estrous cycle, number of corpora lutea and implant rate at any dose level.
Reproductive function: sperm measures:
not specified
Reproductive performance:
not specified
Description (incidence and severity):
In the 500 mg/kg bw group, the number of non-pregnant females was increased although all pairs copulated.

The delivery index was lower than in controls at 500 mg/kg bw/day.

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
100 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
organ weights and organ / body weight ratios
reproductive function (oestrous cycle)
reproductive performance
Remarks on result:
other: No adverse effects 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):
The number of pups and the number of live pups on lactation day 0 and 4 were lower than in the controls at 500 mg/kg bw/day.

No effect on viability of treated rats were observed as compared to control.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No effect on body weight of pups observed as compared to control.
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:
not specified
Histopathological findings:
not specified
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:
100 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
viability
mortality
body weight and weight gain
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 100 mg/kg bw for P and F1 generation when male and female rats were treated with p-methoxybenzaldehyde orally by gavage for approx. 63 days.
Executive summary:

In the combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD TG 422), male and female rats were treated with p-methoxybenzaldehyde in the concentration of 0, 20, 100 and 500 mg/kg bw orally by gavage for approx. 63 days. Epididymidal weight was decreased in males at 500 mg/kg group. The compound showed no adverse effects in terms of estrous cycle, number of corpora lutea and implant rate at any dose level. In the 500 mg/kg bw group, the number of non-pregnant females was increased although all pairs copulated. The delivery index was lower than in controls at 500 mg/kg bw/day. In addition, the number of pups and the number of live pups on lactation day 0 and 4 were lower than in the controls at 500 mg/kg bw/day. No effect on viability of treated rats was observed as compared to control. No effect on body weight of pups observed as compared to control. Therefore, NOAEL was considered to be 100 mg/kg bw for P and F1 generation when male and female rats were treated with p-methoxybenzaldehyde orally by gavage for approx. 63 days.