p-vinylphenol

Endpoint summary

Description of key information

The toxic changes in this fourteen day study are similar to those of phenol (EC 203-632-7 CAS 108-95-2), corrosive and chemical burns at contact site, etc. Reference should be made to Agency for Toxic Substances and Disease Registry (USA) Medical Management Guidelines for Phenol mmg115 2017.

The male animals who given the low dose of 50 mg/kg/bw were assessed as unlikley to be capable of reproduction. Due to the toxicity of the substance a toxicity ro reproduction study is going to be difficult to assess due to the other toxic effects of the substance on the animals.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 September to 11 December 2017

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

according to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

Deviations:

not specified

GLP compliance:

no

Remarks:

This is a range-finding study.

Limit test:

no

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Maruzen Petrochemical Co.Ltd./ Bx 7831WJD
- Expiration date of the lot/batch:
- Purity test date:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Opaque airtight container at -30°C to -10°C
- Stability under test conditions: Stable
- Solubility and stability of the test substance in the solvent/vehicle:
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing:
- Preliminary purification step (if any):
- Final dilution of a dissolved solid, stock liquid or gel:
- Final preparation of a solid:

FORM AS APPLIED IN THE TEST (if different from that of starting material)

TYPE OF BIOCIDE/PESTICIDE FORMULATION (if applicable)

OTHER SPECIFICS:

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Commercial laboratory animal supplier.
- Females: nulliparous and non-pregnant: yes
- Age at study initiation: 7 weeks
- Weight at study initiation:
- Fasting period before study:
- Housing: Barrier-system animal rooms
- Diet: autoclaved pelleted diet ad libitum.
- Water:. ad libitum
- Acclimation period: 6 days


DETAILS OF FOOD AND WATER QUALITY:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 25°C
- Humidity (%): 40 - 70%
- Air changes (per hr): 10-15
- Photoperiod: 12hrs dark / 12hrs light

IN-LIFE DATES: From: To:

Route of administration:

oral: gavage

Details on route of administration:

The animals were orally treated by gavage for 14 days daily with a syringe connected to a catheter at dosing volumes of 5 ml/kg based on body weight

Vehicle:

other: Gum arabic

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

The animals were orally treated by gavage for 14 days daily

Frequency of treatment:

daily

Dose / conc.:

0 mg/kg bw/day (actual dose received)

Remarks:

control

Dose / conc.:

50 mg/kg bw/day (actual dose received)

Dose / conc.:

200 mg/kg bw/day (actual dose received)

Dose / conc.:

500 mg/kg bw/day (actual dose received)

Dose / conc.:

1 000 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

3

Control animals:

yes

yes, concurrent no treatment

Observations and examinations performed and frequency:

Daily before and after dosing

Sacrifice and pathology:

Any surviving animals were euthanised at the end of the study. A full pathological examination took place.

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

In males, salivation, prone position, colonic convulsions, decrease spontaneous locomotion, lacrimation, incomplete eyelid opening were observed and all animals were dead in the 1000 mg/kg.bw group on day 1.
Salivation, prone position, colonic convulsions, decrease spontaneous locomotion, lacrimation, incomplete eyelid opening were observed and all animals were dead in the 500 mg/kg.bw group on day 1.
Salivation, prone position, colonic convulsions, decrease spontaneous locomotion, lacrimation, incomplete eyelid opening were observed and all animals were dead in the 200 mg/kg.bw group on day 1.
Decreased spontaneous locomotion and decreased respiratory rate were observed in one of the 50mg/kg group from day 2 to day 4.

In females, prone position, lateral position, colonic convulsion, decreased spontaneous locomotion, incomplete eyelid opening were observed and all animals died in the 1000 mg/kg group on day 1.
Salivation, lateral position,colonic convulsion, decreased spontaneous locomotion, incomplete eyelid opening were observed and all animals died in the 500 mg/kg group.
Decreased spontaneous locomotion, lacrimation, incomplete eyelid opening, decreased respiratory rate, sub-normal temperature were observed in the 200 mg/kg group on day 1. One animal in the 200 mg/kg group had a shuffling gate from day 2 and salivation, anorexia, decreased stool volume were observed on day 3 and this animal was euthanised on day 3. No abnormalities were observed in the 50 mg/kg group.

Mortality:

mortality observed, treatment-related

Description (incidence):

Reported above

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

For males decreased body weigh was observed in the 200 mg/kg group. No affect was observed on the 50mg/kg group.

In females, decreased body weights were observed in 200 and 50 mg/kg groups.

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

effects observed, treatment-related

Description (incidence and severity):

Details reported above in clinical signs

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

No abnormal organ weights were observed in the surviving animals in the 50 and 200 mg/kg groups

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

In males, reddish change of the wall of the forestomach, pseudomembrane on the mucosa of the glandular stomach, bilateral dark reddish change in the kidneys , dark reddish urine in the urinary bladder were observed in the dead animals of the 1000mg/kg group.
Edematous change and reddish change of the wall of the forestomach, pseudomemberane on the mucosa of the glandular stomach, bilateral dark reddish change and enlargement of the kidneys, blackish contents and dark reddish urine in the urinary tract were observed in dead animals of the 500 mg/kg group.
Elevation of the limiting ridge of the forestomach was observed in the 200 mg/kg group. Staining around the nose and mouth, thickening of the wall of the oesophagus, roughening of the mucosa of the forestomach, distention with gas of the duodenum, jejunum and ileum were observed in one euthanised animal of the 200 mg/kg group. Abnormal necrotic changes were observed in the 50 mg/kg group.

In females, reddish change of the wall of the forestomach, pseudomembrane on the mucosa of the glandular stomach, bilateral dark reddish changes of the kidneys were observed in the dead animals of the 1000 mg/kg group.

Edematous change and reddish change of the wall of the forestomach, bilateral dark reddish change of the kidneys, dark reddish urine in the urinary tract were observed in the dead animals of the 500 mg/kg group.

Elevation of the limiting ridge of the forestomach was observed in the 200 mg/kg group. Thickening of the wall of the oesophagus, edematous change of the wall of the forestomach, pale spleen was observed in one euthanised animal in the 200 mg/kg group. necrotic changes were not observed in the 50 mg/kg group.

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Key result

Dose descriptor:

NOEL

Effect level:

< 50 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

gross pathology

Key result

Critical effects observed:

no

Lowest effective dose / conc.:

50 mg/kg bw/day (actual dose received)

System:

gastrointestinal tract

Organ:

bladder

duodenum

ileum

intestine

jejunum

kidney

oesophagus

stomach

ureter

urethra

Conclusions:

The toxic changes in this fourteen day study are similar to those of phenol (EC 203-632-7 CAS 108-95-2), corrosive and chemical burns at contact site, transient CNS stimulation followed by CNS depression, coma, seizures, diarrhoea, methemoglobinaemia, etc. (ASTDR 2017)

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

50 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Klimisch 1

System:

gastrointestinal tract

Organ:

colon

duodenum

ileum

intestine

jejunum

oesophagus

oral cavity

rectum

stomach

tongue

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

a short-term toxicity study does not need to be conducted because exposure of humans via inhalation in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

a short-term toxicity study does not need to be conducted because exposure of humans via inhalation in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: dermal

Data waiving:

exposure considerations

Justification for data waiving:

a short-term toxicity study does not need to be conducted because exposure of humans via the dermal route in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: dermal

Data waiving:

exposure considerations

Justification for data waiving:

a short-term toxicity study does not need to be conducted because exposure of humans via the dermal route in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

Endpoint conclusion

Endpoint conclusion:

no study available