Formaldehyde, oligomeric reaction products with phenol

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Effects on fertility

Description of key information

Reproductive toxicity study

Based on the data available from different studies, NOAEL was considered to be 1000mg/kg body weight/day ,when male and female rats were treated with test material orally,Thus, comparing this value with the criteria of CLP regulation test material is not likely to classify as reproductive toxicant.

Link to relevant study records

Reference

Endpoint:

reproductive toxicity, other

Remarks:

chronic toxicity study

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

Experimental data of read across substances

Justification for type of information:

Data for the target chemical is summarized based on the structurally similar read across chemicals

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

other: As mention below

Principles of method if other than guideline:

WoE report is based on two reproductive toxicity studies on rats
1 & 2.Reproductive toxicity study of test material was performed on Osborne-Mendel rats.

GLP compliance:

not specified

Limit test:

no

Justification for study design:

No data available

Species:

rat

Strain:

Osborne-Mendel

Details on species / strain selection:

No data available

Sex:

male/female

Details on test animals or test system and environmental conditions:

Study 1 & 2.
TEST ANIMALS
- Housing:The animals were housed individually in wire cages
- Use of restrainers for preventing ingestion (if dermal): yes/no
- Diet (e.g. ad libitum):ad libitum
- Water (e.g. ad libitum):ad libitum

Route of administration:

oral: feed

Vehicle:

other: feed

Details on exposure:

Study 1 & 2.PREPARATION OF DOSING SOLUTIONS: The test chemical was mixed with feed at dose level of 0, 5000, 10000 or 20000 ppm (0, 250, 500 or 1000 mg/Kg/day). 3% propylene glycol was added to control and test diets as a binder to reduce evaporation of the test chemical

DIET PREPARATION
- Rate of preparation of diet (frequency): Weekly
- Mixing appropriate amounts with (Type of food): Details not specified
- Storage temperature of food: No data available

VEHICLE
- Justification for use and choice of vehicle (if other than water): Food
- Concentration in vehicle: 0, 5000, 10000 or 20000 ppm (0, 250, 500 or 1000 mg/Kg/day)
- 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

Duration of treatment / exposure:

Study 1 & 2.
2 year

Frequency of treatment:

Study 1 & 2.
Daily

Details on study schedule:

No data available

Remarks:

0, 5000, 10000 or 20000 ppm (0, 250, 500 or 1000 mg/Kg/day)

No. of animals per sex per dose:

Study 1 & 2.
Total: 96 (48 males and 48 females)
0 mg/Kg bw: 12/sex/dose
250 mg/Kg bw: 12/sex/dose
500 mg/Kg bw: 12/sex/dose
1000 mg/Kg bw: 12/sex/dose

Control animals:

yes, concurrent vehicle

Details on study design:

No data available

Positive control:

No data available

Parental animals: Observations and examinations:

Study 1 & 2.
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Weekly
- Cage side observations checked in table [No.?] were included. General condition

DETAILED CLINICAL OBSERVATIONS: No data
- Time schedule: No data

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly

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

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data

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

Oestrous cyclicity (parental animals):

No data available

Sperm parameters (parental animals):

No data available

Litter observations:

No data available

Postmortem examinations (parental animals):

Study 1 & 2.
GROSS PATHOLOGY: Yes, The tissues of all the rats were examined macroscopically at the time of sacrifice. The viscera were removed and the liver, kidneys, spleen, heart, and testes were weighed.

Postmortem examinations (offspring):

No data available

Statistics:

No data available

Reproductive indices:

No data available

Offspring viability indices:

No data available

Clinical signs:

no effects observed

Dermal irritation (if dermal study):

not specified

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

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:

no effects observed

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

not specified

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

mortality

body weight and weight gain

organ weights and organ / body weight ratios

gross pathology

histopathology: non-neoplastic

Remarks on result:

other: Growth retardation and testicular atrophy was noted

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

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

Behaviour (functional findings):

not specified

Developmental immunotoxicity:

not specified

Remarks on result:

not measured/tested

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

Description (incidence and severity):

The animals were housed individually in wire cages

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

Conclusions:

The NOAEL for reproductive toxicity was considered to be 1000 mg/kg bw/day as No effects on reproductive organ were observed ,When male and female rats were treated with test material orally.

Executive summary:

Data available from different studies were reviewed to determine the reproductive toxicity of testchemical.The studies are as mentioned below:

Study 1 & 2.

Reproductive /chronic oral toxicity study for the 50 -60% structurally and functionally similar read across test compounds

was performed on male and female Osborne-Mendel rats.12 male and 12 female were used in each dose group.The test material was fed through the diet at a concentration of 0, 5000, 10000 or 20000 ppm (0, 250, 500 or 1000 mg/Kg bw) for 2 years.Animals were checked for clinical signs, Food consumption and body weight every week. At the termination of the experiments the rats were sacrificed and exsanguinated.The tissues of all the rats were examined macroscopically at the time of sacrifice. The viscera were removed and the liver, kidneys, spleen, heart, and testes were weighed. These organs, the remaining abdominal and thoracic viscera, and one hind leg, for bone, bone marrow, and muscle, were preserved in 10% buffered formalin-saline solution for histopathological examination. For routine histopathology, sections were embedded in paraffin wax and stained with haematoxylin and eosin.No treatment-related clinical signs and premature deaths were observed. No relevant necropsy findings were noted. No effects on testes weight was noted in treated rats at dose concentration 1000mg/kg bw, Based on the observations made, the no observed Adverse Effect Level (NOAEL) for the test chemical using Osborne-Mendel rats for a duration of 2 year is considered to be 1000 mg/Kg bw.

Thus, comparing this value with the criteria of CLP regulation test material is not likely to classify as reproductive toxicant.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

Data is Klimicsh 2 and from authoritative database

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Data available from different studies were reviewed to determine the reproductive toxicity of test chemical.The studies are as mentioned below:

Study 1 & 2.

Reproductive /chronic oral toxicity study for the test compounds was performed on male and female Osborne-Mendel rats.12 male and 12 female were used in each dose group.The test material was fed through the diet at a concentration of 0, 5000, 10000 or 20000 ppm (0, 250, 500 or 1000 mg/Kg bw) for 2 years.Animals were checked for clinical signs, Food consumption and body weight every week. At the termination of the experiments the rats were sacrificed and exsanguinated.The tissues of all the rats were examined macroscopically at the time of sacrifice. The viscera were removed and the liver, kidneys, spleen, heart, and testes were weighed. These organs, the remaining abdominal and thoracic viscera, and one hind leg, for bone, bone marrow, and muscle, were preserved in 10% buffered formalin-saline solution for histopathological examination. For routine histopathology, sections were embedded in paraffin wax and stained with haematoxylin and eosin.No treatment-related clinical signs and premature deaths were observed. No relevant necropsy findings were noted. No effects on testes weight was noted in treated rats at dose concentration 1000mg/kg bw, Based on the observations made, the no observed Adverse Effect Level (NOAEL) for the test chemical using Osborne-Mendel rats for a duration of 2 year is considered to be 1000 mg/Kg bw.

Thus, comparing this value with the criteria of CLP regulation test material is not likely to classify as reproductive toxicant.

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Justification for classification or non-classification

Thus, comparing this value with the criteria of CLP regulation test chemical is not likely to classify as reproductive toxicant.