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Description of key information

In an acute oral study performed per EPA TSCA 40 CFR 798.1175 the LD50 in the rat was 1.77 g/kg.
In an acute dermal study performed per OECD Test Guideline 402 and OPPTS 870.1200 the LD50 in the rabbit was >2000 mg/kg.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed per EPA TSCA 40 CFR 798.1175 under GLP.
Qualifier:
according to guideline
Guideline:
other: EPA TSCA 40 CFR 798.1175
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Animals were purchased from a USDS approved supplier, Harlan Sprague-Dawley, Inc.
- Age at study initiation: young adult
- Weight at study initiation: 220 – 357 grams
- Fasting period before study: Food withheld overnight prior to dosing.
- Housing: Housed in groups of two in wire mesh suspension cages.

- Diet: Purina laboratory rodent chow, or other comparable diet, provided ad libitum.
- Water: Tap water ad libitum.
- Acclimation period: All animals were acclimated to the laboratory for at least four days before being used.


ENVIRONMENTAL CONDITIONS
- Photoperiod: The animals were maintained on a 12-hour light/12-hour dark cycle.
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
Young adult Sprague Dawley rats were administered the test material as a 25% w/v formulation in corn oil to five groups of male and female rats.
Doses:
5.0, 2.5, 1.25, and 0.625 g/kg
No. of animals per sex per dose:
Two male and two female young Sprague Dawley rats were used per dose group.
Control animals:
no
Details on study design:
Animals were observed several times on the dose day and at least twice daily for 14 days post-dose. Body weights were measured and a gross necropsy was performed on all animals.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1.77 other: g/kg
Mortality:
At the 5.0 g/kg dose level, one male and two females died one day after treatment and the second male died day two post dose. At the 2.5 g/kg dose level, one female died one day post dose, one male died day 3 post dose, and the remaining male and female animals died by day 7 post dose. No deaths were recorded at 1.25 g/kg or lower.
Gross pathology:
Mottled liver and spleen, congested kidneys, distended stomach, darkened intestine filled with red fluid, bright red colored lungs, and blackened spleen were observed at the 5.0 g/kg dose level. Mottled liver and spleen, congested kidneys, distended stomach, reddened and transparent intestines were observed at the 2.5 g/kg dose level. No abnormal gross pathology was noted in animals of the 1.25 g/kg or 0.625 g/kg dose groups.
Other findings:
LD50 = 1.77 g/kg

One male and one female died day 1 post dose at the 1.25 g/kg dose level, however, data from this dose group was replaced with a second 1.25 g/kg dose level due to erroneous sacrificing on day 11 of surviving animals in the first group. Only data from the second dose group at 1.25 g/kg with observations to the completion of the observation period were used to calculate the LD50.

Conclusions:
Under the conditions of this study, the acute oral LD50 of p-Cumylphenol exposure to rats was 1.77 g/kg.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 770 mg/kg bw
Quality of whole database:
A single guideline compliant study conducted under GLP conditions is available. The quality of the database is therefore considered to be good.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed per OECD Test Guideline 402 and OPPTS 870.1200 under GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Remarks:
US EPA GLPs (40 CFR, Part 792) and OECD GLPs
Test type:
other: limit
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
Male and female New Zealand White rabbits were received from Millbrook Breeding Labs. They were 2.00-2.34 kg and at least 12 weeks of age. They were individually housed upon arrival in stainless steel suspended cages with hardwood chip bedding. The animals were acclimated for at least 5 days prior to dosing. Water and feed were provided ad libitum. Room temperature was 68 +/-5 degrees F and the relative humidity ranged between 30-70%. Room lights were on a 12-hour light/dark cycle.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The application sites were prepared by clipping not less than 10% of the body surface on the trunk approximately 24 hours before the application of PCP. PCP was dosed at 2000 mg/kg as received. PCP was slightly moistened and introduced under two single layer thick gauze patches and applied directly to the skin of each animal. Animals were immobilized and the patches were secured in place by wrapping the entire trunk of the animal with an impervious bandage.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5/sex/dose
Control animals:
no
Details on study design:
After completion of the 24-hour exposure period, the wrapping was removed and the skin was gently wiped and rinsed with water.
The animals were observed frequently during the first day and then clinical examinations were made at least once a day. The animals were also examined for signs of erythema and edema after the exposure period as per the Draize method. Animals were weighed on Days 0 (pre-dose), 7 and 14.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality was observed.
Clinical signs:
other: No overt signs of clinical toxicity were observed in any animal. No signs of erythema or edema were observed in any animals.
Gross pathology:
All animals were observed as normal at necropsy.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
PCP was evaluated for its potential to produce systemic toxicity or death after a single topical 24-hour application at 2000 mg/kg to the skin of rabbits. The rabbit dermal LD50 was determined to be >2000 mg/kg-bw.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
A single guideline compliant study conducted under GLP conditions is available. The quality of the database is therefore considered to be good.

Additional information

The acute oral toxicity was investigated in a fixed dose procedure performed per EPA TSCA 40 CFR 798.1175 under GLP conditions (Hill Top Biolabs, Inc., 1990).

Young adult Sprague Dawley rats were administered the test material as a 25 % w/v formulation in corn oil to five groups of male and female rats at dose levels of 5.0, 2.5, 1.25, and 0.625 g/kg (two rats per sex per dose).

Under the conditions of this study, the acute oral LD50 was 1.77 g/kg.

 

The acute dermal toxicity was investigated in a procedure performed per OECD Test Guideline 402 and OPPTS 870.1200 under GLP conditions (Toxikon Corporation, 2003).

Five male and five female New Zealand White rabbits were exposed to the test material in an occlusive fashion for 24 hours at a limit dose of 2000 mg/kg.

Under the conditions of this study, the acute dermal LD50 was >2000 mg/kg bw.


Justification for selection of acute toxicity – oral endpoint
Only one study available.

Justification for selection of acute toxicity – dermal endpoint
Only one study available.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the substance requires classification with respect to acute toxicity via the oral route as Acute Tox Category 4 (H302: Harmful if swallowed).