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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
reproductive toxicity, other
Remarks:
Carcinogenic effect
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:
Study report from National Cancer Institute

Data source

Reference
Reference Type:
secondary source
Title:
Evaluation of Carcinogenicity, Teratogenecity &Mutagenic Activities of Selected Pesticides and Industrial Chemicals. Volume I: Carcinogenic Study
Author:
Kotin et al
Year:
1968
Bibliographic source:
National Cancer Institute Division of Cancer Cause &Prevention Carcinogenesis Program Bethesda,1968

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
other: As mentioned below
Principles of method if other than guideline:
Long term toxicity and carcinogenicity study of test material was performed in mice.
GLP compliance:
not specified
Limit test:
no
Justification for study design:
No data available

Test material

Constituent 1
Chemical structure
Reference substance name:
4-methoxyphenylacetic acid
EC Number:
203-166-4
EC Name:
4-methoxyphenylacetic acid
Cas Number:
104-01-8
Molecular formula:
C9H10O3
IUPAC Name:
(4-methoxyphenyl)acetic acid
Test material form:
solid: crystalline
Details on test material:
- Name of test material (as cited in study report): P-methoxy phenyl acetic acid- Molecular formula (if other than submission substance): C9H10O3- Molecular weight (if other than submission substance): 166.175 g/mole - Smiles notation (if other than submission substance): c1(ccc(OC)cc1)CC(O)=O- InChl (if other than submission substance): 1S/C9H10O3/c1-12-8-4-2-7(3-5-8)6-9(10)11/h2-5H, 6H2, 1H3, (H,10,11)- Substance type: Organic- Physical state: Solid
Specific details on test material used for the study:
No data available

Test animals

Species:
mouse
Strain:
B6C3F1
Details on species / strain selection:
No data available
Sex:
female
Details on test animals or test system and environmental conditions:
- Source:Cumberland View Farms- Age at study initiation: 7 dyas - Weight at study initiation: 10-19 gms Fasting period before study:- Housing: Animals were 6 mice to a cage. 2160 mice couli be housed in each room.- Diet (e.g. ad libitum): food , ad libitum- Water (e.g. ad libitum): water, ad libitum - Acclimation period:ENVIRONMENTAL CONDITIONS- Temperature (°C):- Humidity (%):- Air changes (per hr): A dual duct high velocity sy~tem was used for heating, ventilation and air conditioning.Unidirectional air-flow minimized room to room contamination with absolute filtration of all incoming air to remove particulate matter of 0.3 micron diameter or greater.- Photoperiod (hrs dark / hrs light):

Administration / exposure

Route of administration:
other: oral administration by stomach tube and after dose is administer through diet.
Type of inhalation exposure (if applicable):
not specified
Vehicle:
other: Diet(ground feed) and 0.5% gelatin
Details on exposure:
oral administration by stomach tube from day 7 to 28 and after dose is administered through diet for 18 months
Details on mating procedure:
No data available
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
18 months
Frequency of treatment:
Daily
Details on study schedule:
No data available
Doses / concentrations
Remarks:
0 and 215 mg/kg bw/day
No. of animals per sex per dose:
Total: 1500 mg/kg bw :18 Females0 mg/kg bw :18 Females215 mg/kg bw :18 FemalesPositive controlEthyl carbamate: 24 FemalesAmitrol: 18 FemalesE:thylene imine: 18 FemalesAramite: 18 FemalesDihydrosafrole: 18 FemalesSafrole: 18 Females
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: The basic concept of the dosage choice was the use of a maximum tolerated dose. The calculated dose was not adjusted to the changing body weight during the three weeks of stomach tubing but a single adjustment was made at the time of conversion from stomach tube to mixture in the feed.- Rationale for animal assignment (if not random): Dosing of individual mice was based on the average weight within a single group and, in the case of repetitive administration, was based on starting weights and not adjusted as the study continued.( An exception to this was the recalculation in the definitive study, at the time of weaning when administration was converted from daily stomach tubing to incorporation in the diet.)
Positive control:
Ethyl carbamate, Amitrol, E:thylene imine, Aramite, Dihydrosafrole and Safrole were used as positive control.

Examinations

Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: Yes - Time schedule:Daily - Cage side observations checked in table [No.?] were included: Mortality and morbidity were observed. DETAILED CLINICAL OBSERVATIONS: Yes - Time schedule: palpated weekly at time of weighing for enlargement of liv,~r and spleen, or any subcutaneous tumor. BODY WEIGHT: Yes - Time schedule for examinations: six animals in each cage were weighed once a week.
Oestrous cyclicity (parental animals):
No data available
Sperm parameters (parental animals):
No data available
Litter observations:
No data available
Postmortem examinations (parental animals):
Gross pathology and histopathology were examined.
Postmortem examinations (offspring):
No data available
Statistics:
Chi square test &Yates Correction were used
Reproductive indices:
No data available
Offspring viability indices:
No data available

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
mortality observed, non-treatment-related
Description (incidence):
No effect on survival of treated female mice were observed as compared to control.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Body weight gain was observed with the increase in duration of treatment.
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:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
not specified

Details on results (P0)

MORTALITY (PARENTAL ANIMALS): No effect on survival of treated female mice were observed as compared to control. BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS): Body weight gain was observed with the increase in duration of treatment. TEST SUBSTANCE INTAKE (PARENTAL ANIMALS):No data availableREPRODUCTIVE FUNCTION: ESTROUS CYCLE (PARENTAL ANIMALS):No data available REPRODUCTIVE FUNCTION: SPERM MEASURES (PARENTAL ANIMALS):No data availableREPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS):Not Disrupted sexual functionORGAN WEIGHTS (PARENTAL ANIMALS):No data availableGROSS PATHOLOGY (PARENTAL ANIMALS): No gross pathological changes were observed in treated female mice.HISTOPATHOLOGY (PARENTAL ANIMALS): No fibroadenoma and carcinoma mammary gland were observed in treated female mice as compared to control.

Effect levels (P0)

Key result
Dose descriptor:
NOAEL
Effect level:
> 215 other: mg/kg
Based on:
test mat.
Sex:
female
Basis for effect level:
mortality
gross pathology
histopathology: non-neoplastic
Remarks on result:
other: No effects on reproductive parameters

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:
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
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:
other: not specified
Generation:
other: not specified
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: not specified
Remarks on result:
not measured/tested

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 > 215 mg/kg bw when B6C3F1 female mice by using test material for 18 months.
Executive summary:

In a reproductive toxicity study, B6C3F1 female mice were treated with test material in the concentration of 0 and 215 mg/kg bw/day in 0.5% gelatin for 7 to 28 day and after dose is administer through diet at 560 ppm for 18 months. Body weight gain was observed with the increase in duration of treatment. No gross pathological changes were observed in treated female mice. In addition, no fibroadenoma and carcinoma mammary gland were observed in treated female mice as compared to control. Therefore, NOAEL was considered to be > 215 mg/kg bw when B6C3F1 female mice by using test material for 18 months.