Phenol, paraalkylation products with C10-15 branched olefins ( C12 rich) derived from propene oligomerization, calcium salts, sulfurized, including distillates (petroleum), hydrotreated, solvent-refined, solvent-dewaxed, or catalyc dewaxed, light or heavy paraffinic C15-C50

Endpoint summary

Description of key information

Oral exposure: 
In a study conducted in line with OECD guideline 401 under condistions of GLP, the test material was evaluated for its acute oral toxicity potential in male and female rats when administered as a single gavage dose at a level of 5,000 mg/kg of body weight. No deaths occurred during the study. The estimated oral LD50 values for male and female rats were determined to be greater than 5,000 mg/kg. 
Dermal exposure:
The test material was evaluated for its acute dermal toxicity potential in five male and five female rats when administered as a single topical application at a level of 2,000 mg/kg of body weight for a 24-hour exposure period. The study was conducted according to OECD 402. All rats were observed for clinical signs and mortality at 1, 2.5, and 4 hours following treatment and for 14 days thereafter. No deaths occurred during the study. The estimated dermal LD50 values for male and female rats were determined to be greater than 2,000 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

Study period:

11th September 1996 to 24th January 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study following GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: approximately 9 to 10 weeks of age
- Weight at study initiation: 209 to 296 g
- Fasting period before study: yes, 17 to 20 hours before test material administration
- Housing: After test material administration, the animals were individually housed in suspended screen-bottom stainless steel cages.
- Diet/water (e.g. ad libitum): The animals were provided continuous access to Laboratory Rodent Diet #5001, PMI Feeds, Inc., and water except for 17 to 20 hours before test material administration when food, but not water, was withheld. The feed is routinely analyzed by the manufacturer for nutritional components and environmental contaminants. Samples of the water are periodically analyzed. There were no known contaminants in the feed or water at levels that could be expected to interfere with or affect the results of the study.
- Acclimation period: the animals were acclimated for a period of at least 7 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 50% ± 20%,
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark lighting cycle

IN-LIFE DATES: From: To: 11th to 25th September 1996

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.5 g/mL
- Amount of vehicle (if gavage): The prepared test material mixture appeared to be a suspension. An individual dose was calculated for each animal based on its fasted body weight and administered by gavage at a volume of 10 mL/kg of body weight.

Doses:

limit dose of 5000 mg/kg b. wt

No. of animals per sex per dose:

5 male/female

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: Clinical observations were conducted at 1, 2.5, and 4 hours after test material administration and daily thereafter for 14 days. Mortality checks were conducted twice a day (morning and afternoon) for 13 days after test material administration and again the morning of Day 14.
- Frequency of observations and weighing: Body weights were determined before test material administration (Day 0), at Day 7, at termination of the in-life phase (Day 14).
- Necropsy of survivors performed: yes, at termination of the in-life phase, all animals were euthanized by an overexposure to carbon dioxide, subjected to an abbreviated gross necropsy examination, and any abnormalities were recorded. After necropsy, the animals were discarded and no tissues were saved as there were no grossly abnormal tissues.

Statistics:

No statistical analyses were required by the protocol.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed during the study. The estimated oral LD50 values for male and female rats were determined to be greater than 5,000 mg/kg of body weight.

Clinical signs:

other: Clinical signs of toxicity included red-stained face, soft stool, and dark/yellow-stained urogenital area. All animals returned to a normal appearance by Day 7 after treatment.

Gross pathology:

There were no lesions observed at the terminal necropsy.

The acute oral toxicity of the test material was evaluated in male and female rats when administered as a single gavage dose at a level of 5,000 mg/kg of body weight. No mortality occurred during the study. The estimated oral LD50 values for male and female rats were determined to be greater than 5,000 mg/kg. Clinical signs of toxicity included red-stained face, soft stool, and dark/yellow-stained urogenital area. All animals returned to a normal appearance by Day 7 after treatment. All animals exhibited body weight gain throughout the study. The gross necropsy examinations at termination revealed no visible lesions,

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LD50 > 5000 mg/ kg b. wt. (males and females)

Executive summary:

In a study conducted in line with OECD guideline 401 under condistions of GLP, the test material was evaluated for its acute oral toxicity potential in male and female rats when administered as a single gavage dose at a level of 5,000 mg/kg of body weight. No deaths occurred during the study. The estimated oral LD50 values for male and female rats were determined to be greater than 5,000 mg/kg. Clinical signs of toxicity included red-stained face, soft stool, and dark/yellow-stained urogenital area. All animals returned to a normal appearance by Day 7 after treatment. All animals exhibited body weight gain throughout the study. The gross necropsy examinations at termination revealed no visible lesions.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

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

Study period:

20th September to 4th October 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study following GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

not specified

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Young adult albino rats of the Crl:CD®(SD)BR strain were procured from Charles River Laboratories, Inc., Portage, Michigan on September 3 and 9, 1996.
- Age at study initiation: approximately 7 to 11 weeks of age
- Weight at study initiation: 236 to 286 g
- Housing: After test material administration, the animals were individually housed.
- Diet (e.g. ad libitum): The animals were provided continuous access to Laboratory Rodent Diet #5001, PMI Feeds, Inc. The feed is routinely analyzed by the manufacturer for nutritional components and environmental contaminants. Samples of the water are periodically analyzed. There were no known contaminants in the feed or water at levels that could be expected to interfere with or affect the results of the study.
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: After receipt, the animals were acclimated for a period of at least 7 days. During acclimation, the animals were separated by sex and group housed in suspended screen-bottom stainless steel cages.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19° to 25°C
- Humidity (%): 50% ±20%
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark lighting cycle

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: The test material was applied to the test site at a rate of approximately 0.014 g/cm2 in a thin and uniform layer.
- Type of wrap if used: The area of application (approximately 36 cm2) was covered with a 4-ply 6-cm x 6-cm gauze patch secured with four strips of Micropore' surgical tape. The trunk of the animal was then loosely overwrapped with a sheet of perforated plastic film that was secured on both ends with strips of Elastoplast® tape to provide a semiocclusive dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the 24-hour exposure period, the bandages were removed and the residual test material removed from test sites using mineral oil followed by liquid Ivory® soap mixed with warm tap water. The test sites were then rinsed with clean tap water and dried with disposable paper towels.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The undiluted test material was applied to the intact skin on each animals' back at a dose level of 2,000 mg/kg of body weight.

Duration of exposure:

24 hours

Doses:

2000 mg/kg b. wt

No. of animals per sex per dose:

Five

Control animals:

not specified

Details on study design:

The route of administration was semi-occluded topical application.

The test material was administered undiluted to shaved, intact skin (approximately 36 cm2) at a limit dose of 2000 mg/kg b. wt. and covered with a
semi-occlusive dressing. After 24 hours the dressing was removed and the site washed with mineral oil followed by a mild soap solution. The animals were held for 14 days and observed at 1, 2.5, and 4 hours after test material application and twice daily thereafter. Dermal irritation was scored 30 minutes after dressing removal and on days 3, 7, 10 and 14. Individual body weights were recorded prior to dosing and on days 7 and 14 after dosing. The animals were euthanized by CO2 inhalation at the conclusion of the observation period and examined for gross pathological changes. Tissues
with macroscopic abnormalities were preserved for microscopic examination.All guideline recommendations were exceeded.
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: Clinical observations were conducted at approximately 1, 2.5, and 4 hours after test material administration and daily thereafter for 14 days. Mortality checks were conducted twice a day (morning and afternoon) for 13 days after test material administration and again the morning of Day 14.
Body weights were determined before test material application (Day 0), at Day 7, and at termination of the in-life phase (Day 14).
The initial dermal irritation reading was made 30 minutes after removal of the test material according to the Draize technique (recorded as the Day 1 score). Subsequent readings of dermal irritation were made on Days 3, 7, 10, and 14.
- Necropsy of survivors performed: yes, at termination of the in-life phase, all animals were euthanized by an overexposure to carbon dioxide, subjected to an abbreviated gross necropsy examination, and any abnormalities were recorded. After necropsy, the animals were discarded and no tissues were saved as there were no grossly abnormal tissues.

Statistics:

No statistical analyses were required by the protocol.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed during the study.

Clinical signs:

other: All animals appeared normal throughout the study.

Gross pathology:

There were no lesions observed at the terminal necropsy.

Other findings:

Dermal irritation (based on the most severe score for each animal at any time point) consisted of only slight erythema reactions in 1 male and 1 female. No other dermal irritation was observed.

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The estimated dermal LD50 values for male and female rats were determined to be greater than 2,000 mg/kg.

Executive summary:

The test material was evaluated for its acute dermal toxicity potential in five male and five female rats when administered as a single topical application at a level of 2,000 mg/kg of body weight for a 24-hour exposure period. The study was conducted according to OECD 402. All rats were observed for clinical signs and mortality at 1, 2.5, and 4 hours following treatment and for 14 days thereafter. No deaths occurred during the study. The estimated dermal LD50 values for male and female rats were determined to be greater than 2,000 mg/kg. All animals appeared normal during the study. All animals exhibited body weight gain during the study with the exception of 1 female which exhibited an insignificant weight loss of 6 g during the second week. The test material produced only slight dermal reactions in two animals which cleared in these animals by Day 7. The gross necropsy examinations at termination revealed no visible lesions.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Oral:

Value for CSA:> 5000 mg/kg

In the key study for oral exposure (Glaza, 1997, Report number: CHW 60803939) the study was conducted according to OECD Guideline 401 (Acute Oral Toxicity). The study was conducted in line with GLP. A reliability rating of 1 according to the criteria of Klimisch, 1997. This was considered to be the most reliable study.

 

There are also supporting studies for this endpoint:

 

- The Costello BA, Murray RB & Moore study, 1983 (Biosearch report number: 83-3824A) was conducted according to CFR 1500.3 Federal Hazardous Substances Act, rather than an OECD guideline. The study was considered to have a reliability rating of 2, according to the criteria of Klimisch, 1997.

The test article, when administered to 5 male and 5 female rats, had an acute oral LD50 of >5000 mg/kg.

 

- The Rittenhouse et al study, 1975 (Chevron report number: 672/XVIII:111) was considered to have a reliability rating of 2, according to the criteria of Klimisch, 1997.

The test article, when administered to 10 male rats, had an acute oral LD50 of >5000 mg/kg.

 

- The Costello BA, Murray RB & Moore study, 1983 (Biosearch report number: 83-3809A) was conducted according to CFR 1500.3 Federal Hazardous Substances Act, rather than an OECD guideline. The study was considered to have a reliability rating of 2, according to the criteria of Klimisch, 1997.

The test article, when administered to 5 male and 5 female rats, had an acute oral LD50 of >5000 mg/kg.

 

- The Kruke et al study, 1972 (Chevron report number: 359/XII:52) was not conducted to a recognised guideline and only limited information was presented. The study was considered to have a reliability rating of 2, according to the criteria of Klimisch, 1997.

The LD50 can be estimated to be >5000 mg/kg.

 

- The WARF INSTITUTE, INC. study, 1972 (Report number: 2060447) was not conducted to a recognised guideline and only limited information was presented. The study was considered to have a reliability rating of 2, according to the criteria of Klimisch, 1997.

It is estimated that the LD50 is between 10 and 20 g/kg.

 

- Supporting information, obtained from the 2000 European Chemicals Bureau IUCLID Data Set for the substance is presented, however this is secondary source information and is considered to have a reliability rating of 4, according to the criteria of Klimisch, 1997.

Dermal:

Value for CSA:> 2000 mg/kg

In the key study for dermal exposure (Glaza, 1997, Report number: CHW 60803940) the study was conducted according to OECD Guideline 402 (Acute Dermal Toxicity). The study was conducted in line with GLP. A reliability rating of 1 was assigned according to the criteria of Klimisch, 1997. This was considered to be the most reliable study.

 

There are also two supporting studies for this endpoint:

 

- The Kruke et al study, 1972 (Chevron report number: 359/XII:52) was not conducted to a recognised guideline and only limited information was presented. The study was considered to have a reliability rating of 2, according to the criteria of Klimisch, 1997.

The LD50 was estimated to be > 5000 mg/kg.

 

- The Rittenhouse et al study, 1975 (Chevron report number: 672/XVIII:111) was not conducted to a recognised guideline and only limited information was presented. The study was considered to have a reliability rating of 2, according to the criteria of Klimisch, 1997.

The LD50 was estimated to be > 5000 mg/kg.

Justification for classification or non-classification

Oral:

The key parameter chosen for acute toxicity for the oral route was greater than the classification criteria, therefore classification for acute toxicity was not considered to be necessary.

Dermal:

The key parameter chosen for acute toxicity for the dermal route was greater than the classification criteria , therefore classification for acute toxicity was not considered to be necessary.