2-hydroxybenzoic acid 2-butyloctyl ester

Endpoint summary

Description of key information

Adequate guideline acute oral and dermal toxicity studies in rats indicate a low order of acute toxicity for the test substance.

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:

5 April 1996 to 19 April 1996 (in life)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: Federal Hazardous Substances Act (USA) - 16 CFR 1500.3(c)(2)(i)

GLP compliance:

yes (incl. QA statement)

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: A USDA licensed supplier
- Weight at study initiation: male, 200-300 g; female, 200-300 g
- Fasting period before study: 18 hours
- Housing: in suspended stainless steel wire mesh cages in a temperature controlled room
- Diet (ad libitum): standard laboratory feed for rodent
- Water (ad libitum): city water
- Acclimation period: at least 4 days prior to the start of testing


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 70 deg F +/- 2 deg F


IN-LIFE DATES: From: 5 April 1996 To: 19 April 1996

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test material was used as received. The test substance was measured by syringe and dosed via syringe and intubation tube. The dose was calculated as follows:

Dose Volume (ml) = Animal Weight (kg) x Dose (g/ml) / Test Material Density or Concentration (g/ml)

Doses:

5000 mg/kg bwt

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Test Duration/Observations:

Animals were examined immediately after dosing, 4 hours after dosing, and then twice daily for a maximum of 14 days.

Animal Preparation:

The rats were fasted overnight for approximately 18 hours prior to dosing. Water was available ad libitum.

Types of Observations:

Cageside observations included: skin and fur, eyes and mucous membrane, respiratory system, circulatory system, autonomic and central nervous system, behavior pattern and the onset of tremor, convulsions, salivation, lethargy, sleep and coma.

Gross Pathology:

This was performed on all animals at the time of death. All gross pathological observations were recorded.

Analysis of Data:

The animal's response when exposed to the test substance will include the incidence, severity and reversibility of the following: behavior abnormalities, clinical abnormalities, gross lesions, body weight changes, effects on mortality, and any other toxicological effects.

Evaluation:

As defined in FHSA 16 CFR 1500.3(c)(2)(l), if a dose of 5 g/kg bwt produces no compound related mortality in 5 or more animals, the test material is not considered toxic.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

No mortality occurred during the course of this study.

Clinical signs:

other: At 4 hours post dosing and on days 1 and 2, all animals had yellow anogenital staining. On days 3 and 4, a single female had yellow anogenital staining and appeared dehydrated on day 3. There were no other clinical observations noted.

Gross pathology:

There were no gross abnormalities observed in any of the animals at necropsy.

Conclusions:

The submitted test material when administered as supplied at a single oral dosage level of 5 g/kg bwt did not produce compound-related mortality in half or more of the animals; therefore, the test material is not considered toxic according to definitions listed in the FHSA - 16 CFR 1500.3(c)(2)(l).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The quality of the key study for acute oral toxicity in rats was sufficient to fulfill the requirements for this endpoint.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

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:

20 February 1998 to 19 August 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

dated February 24, 1987

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Cr1:CD(SD)BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Kingston, New York 12484 (USA)
- Age at study initiation: young adults at least 9-12 weeks old
- Weight at study initiation: males, 275-315 g; females, 214-221 g
- Fasting period before study: none
- Housing: group housed (6/cage) during acclimation; individually in suspended stainless steel cages with wire mesh bottoms during the study
- Diet (ad libitum): Certified Rodent Diet No. 5002 (PMI Nutrition International, St. Louis, Missouri, USA)
- Water (ad libitum): municipal water supply (Elizabethtown Water Company, Westfield, New Jersey, USA).
- Acclimation period: 9 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24
- Humidity (%): 28-62
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12 (automated timer)


IN-LIFE DATES: From: 26 February 1998 To: 12 March 1998

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Preparation of animals:

Approximately 24 hours before dosing, the hair of each rat was closely clipped from the trunk (dorsal surface area and sides from scapular to pelvic areas) with an electric clipper exposing at least 10% of the body surface area (approximately 6 cm x 6 cm). The skin was not abraded.

Administration:

Applied to the clipped skin of the dorsal trunk surface. Doses were calculated using pretest (Day 1) body weights. The material was applied directly onto the exposed skin of the animal and spread evenly over the entire area. A layer of 8-ply gauze was then placed over the application site. The gauze was then covered with impervious plastic and secured with an Elastoplast bandage. Following approximately 24 hours, the wrappings were removed and the site wiped free of excess test material with gauze moistened with 0.9% saline.

Duration of exposure:

approximately 24 hours

Doses:

A single dose level, 2000 mg/kg bwt

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Duration of study:

A single dose was administered to each animal, followed by 14 days of observations.

Observations:

Observations for mortality were made twice daily. Each animal was removed from its cage and observations of general condition, skin and fur, eyes, nose, oral cavity, abdomen and external genitalia as well as evaluations of respiration and palpation for tissue masses were made. All abnormalities, including severe dermal effects, were recorded.

Evaluation of dermal irritation:

Dermal irritation was scored (Table 1) approximately 60 minutes, 24, 48, and 72 hours after bandage removal and daily thereafter. At each interval, treatment sites were evaluated for erythema and edema and other evidence of dermal irritation. Special notation was made of tissue damage, eschar, other evidence of irreversible alteration of tissue structure, and any other dermal abnormalities.

Body weights:

These were obtained on Day 0 (at time of clipping), on Day 1 (just before dosing) and on Days 8 and 15.

Food consumption:

Each animal’s quantity of feed was visually inspected, and any qualitative decreases in food consumption, relative to other animals on test, were recorded.

Postmortem:

At study termination (Day 15), all animals were euthanatized by exsanguination following carbon dioxide anesthesia. Necropsy included macroscopic examinations of all external surfaces and orifices, the organs and tissues of the cranial, thoracic, abdominal and pelvic cavities and neck and remainder of the carcass. All abnormalities were recorded and any tissues with lesions were saved.

Statistics:

Based on the study results, calculation of an LD50 value was not applicable.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

There was no mortality reported.

Clinical signs:

other: Six of the ten animals exhibited slight red stains on the snout on the day of dosing. All animals were free of clinical signs by Day 2. The test material did not cause dermal irritation with no irritation scores other than 0 reported during the study.

Gross pathology:

A single animal at necropsy exhibited slightly firm, slightly white discolored lungs. All other animals were free of macroscopic abnormalities.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the dermal LD50 of Hallbrite BHB in rats is greater than 2000 mg/kg bwt.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The quality of the key study for acute dermal toxicity in rats was sufficient to fulfill the requirements for this endpoint.

Additional information

Acute Oral Toxicity

The acute toxicity of the test substance was determined according to Federal Substance Act (USA) - 16 CFR 1500.3(c)(2)(i). Groups of 5 male and female rats were administered a single gavage limit dose of the undiluted test substance of 5,000 mg/kg bw. Animals were observed twice daily for up to 14 days. There was no mortality reported in the study. At 4 hours post dosing and on days 1 and 2, all animals displayed yellow anogenital staining. On days 3 and 4, a single female had yellow anogenital staining and appeared dehydrated on day 3. There were no other clinical observations noted. There were no gross abnormalities observed in any animals at necropsy.

Acute Inhalation Toxicity

This requirement is waived based on the low vapor pressure of the subject material, which precludes significant exposure by this route.

Acute Dermal Toxicity

The acute dermal toxicity of the test material was determined in a test following OECD guideline 402 (Acute Dermal Toxicity). The undiluted test substance was applied for 24 hours under occlusive wrap to groups of 5 male and 5 female rats at a limit dose of 2,000 mg/kg bw. Animals were observed for 14 days following exposure. There was no mortality reported. Six of the ten animals exhibited slight red staining of the snouts on the day of dosing. All animals were free of clinical signs on Day 2. The test material did not affect body weights or body weight gains. The test material did not cause dermal irritation with no irritation scores other than 0 reported during the study. At necropsy, a single animal exhibited slightly firm, slightly white discolored lungs. All other animals were free of macroscopic abnormalities.

Justification for selection of acute toxicity – oral endpoint

In a guideline study conducted according to the Federal Hazardous Substances Act (USA) (16 CFR 1500.3(c)(2)(i)) and following accepted GLP standards, the test substance produced no mortality in either male or female rats administered at a limit dose of 5,000 mg/kg bw following gavage administration..

Justification for selection of acute toxicity – inhalation endpoint

Exposure of humans via inhalation is unlikely given the low vapor pressure of the test substance. In addition, there is no possibility of exposure to aerosols, particles or droplets of inhalable size.

Justification for selection of acute toxicity – dermal endpoint

In an OECD guideline 402 Acute Dermal Toxicity study conducted according to accepted GLP standards, the test substance produced no mortality in either male or female rats after dermal administration under occlusive wrap.

Justification for classification or non-classification

Based on the acute toxicity of the subject chemical, it would not be rated for acute oral toxicity under either the EU Directive 67/548/EEC or under the EU CLP (Regulation (EC) 1272/2008).

Based on the acute toxicity of the subject chemical, it would not be rated for acute dermal toxicity under either the EU Directive 67/548/EEC or under the EU CLP (Regulation (EC) 1272/2008).