Tall oil, potassium salt

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 August 2005 to 7 September 2005

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: CrI:CD(SD)IGS BR
- Age at study initiation: Approximately 8 weeks at the time of administration.
- Weight at study initiation: 174 to 194 g
- Fasting period before study: Yes. The feed was withdrawn the evening before the administration of the test material and was offered again about three hours post administration.
- Housing: Single caging (39 x 23 cm bottom area, 18 cm high) with wire mesh lids.
- Diet (e.g. ad libitum): feed gamma irradiated with 25 kGyCo, ad libitum.
- Water (e.g. ad libitum): Tap water from an automatic watering system, ad libitum.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Average of 22.0 °C
- Humidity (%): Average of 70.6 %
- Air changes (per hr): 12 per hour
- Photoperiod (hrs dark / hrs light): Artificial light from 6 a.m. to 6 p.m.

IN-LIFE DATES: From: 17 August 2005 To: 7 September 2005

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): The individual dose volumes were calculated using the bodyweights determined on the day of the administration.
- Justification for choice of vehicle: The test material was not soluble in water.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: As no prior information on the toxicity of the test material was available, a starting dose of 300 mg/kg bodyweight was chosen. The solutions were freshly prepared before dosing and were administered within 20 minutes.

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

3 female animals per step (6 animals in total per dose level)

Control animals:

no

Details on study design:

The test material was administered sequentially to groups of 3 animals per step, using a starting dose of 300 mg/kg. After the initial group of rats had been dosed, a second group of animals received the test material at a dose level of 300 mg/kg.
In the absence of any toxicological effects, the test material was administered to a third group of animals at a dose level of 2000 mg/kg. A fourth and final group of animals then received the test material at the 2000 mg/kg dose level.

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were performed within the periods 0 to 0.5, 0.5 to 1, 1 to 2, 2 to 4 and 4 to 6 hours after administration of the test material and then at least once a day for a total of 2 weeks. Observations included but were not limited to changes in skin, fur, eyes, the occurrence of secretions and excretions, autonomic activity, changes in gait, posture and the presence of convulsions.
Bodyweights were determined before administration, 7 days post administration and 14 days post administration. Body weight gain was calculated for each week of the study, i.e. between 0 and 7 days and between 7 and 14 days following dosing.
- Necropsy of survivors performed: yes. The animals were killed by inhalation of 80 % CO2 + 20 % air and subjected to a necropsy including a gross pathological examination.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity were observed.

Gross pathology:

No abnormalities were noted at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the acute oral LD50 of the substance was determined to be >2000 mg/kg bw

Executive summary:

The acute oral toxicity potential of the test substance in Sprague-Dawley rats was determined according to OECD Guideline 423 and EU Method B.1 under GLP conditions. The test substance was administered by oral gavage as a solution in corn oil; the dosing was performed sequentially to groups of 3 animals per step using a starting dose of 300 mg/kg bw and 2000 mg/bw as the second dose. The animals were observed for 14 days. There was no mortality and no clinical signs were observed. All animals showed expected gains in bodyweight throughout the observation period. Under the conditions of this study, the acute oral LD50 of the substance in rats was determined to be >2000 mg/kg bw.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted prior to GLP and current standardised guidelines, however it adheres to generally accepted scientific principles with thorough reporting, allowing for an accurate assessment of the quality of the data.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: Albino rats of a Wistar strain
- Age at study initiation: Adult
- Weight at study initiation: 200 to 300 g
- Fasting period before study: 16 hours prior to administration of test material
- Housing: one per cage in metabolism cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Route of administration:

oral: gavage

Vehicle:

other: distilled water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg bw

Doses:

0, 2100, 2400, 2700, 3300, 3600 and 3900 mg/kg bw

No. of animals per sex per dose:

No data on number of animals per sex per dose - the overall study was conducted on 109 animals.

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs were noted at hourly or other intervals during the acute phase of the toxic reaction and as death appeared imminent. Bodyweight, food and water intake, urine volume and urinalyses, and colonic temperature were recorded upon survivors at intervals of 24 hours after drug administration until recovery was obvious.
- Necropsy of survivors performed: yes. Autopsies were performed upon non-survivors, a group of 13 survivors at study termination and upon controls. Gross pathologic observations and wet weight and water levels of organs were recorded. Blocks of tissue were stained with haematoxylin-phloxine-saffron and examined microscopically.

Statistics:

All data were subjected to t tests of significance of differences between means after the methods of Croxton (1953).
The regression line of the data and its standard error were calculated by the method of least squares.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 020 mg/kg bw

Based on:

test mat.

Mortality:

Death occurred in approximately half of the rats. By plotting dosage on the ordinate and percent mortality on the abscissa, regression was found to be linear at the doses selected.
Death occurred in less than 2 hours in 62 % of instances, in 3 to 6 hours in 25 %, and in 7 to 12 hours in 13 %. The mean ± standard deviation interval to death was 3.3 ± 3.2 hours. Deaths delayed beyond 6 hours occurred only in rats receiving doses of 3300 mg/kg and over.

The cause of death in these rats was respiratory failure with or without convulsions, accompanied by gastroenteritis, dehydration of most organs and renal tubular necrosis.

Clinical signs:

other: The most common pre-mortem clinical sign was prostration. Tonic-clonic convulsions occurred in one third of the animals. Survivors recovered quickly from the toxic effects of the test material. At about the time their littermates were dying, one third o

Gross pathology:

At autopsy of the non-survivors, the parietal cells, mucous neck cells, and surface epithelium of the pyloric stomach were shrunken and there was loss of weight of this organ. There were also areas of capillary and venous congestion in the lamina propria and submucosa in the pyloric stomach and occasional haemorrhage and necrosis of the surface epithelium. The columnar epithelium covering the intestinal villi was shrunken and the goblet cells dilated. There were areas of early necrosis in the renal tubular epithelium. The heart was dilated with blood and the respiratory alveoli were frequently collapsed. The spleen was contracted. Other organs were normal in histological appearance but most of them had lost weight due principally to loss of water.

The group of survivors autopsied at study termination showed no evidence of residual pathology. All of the organs (except the heart) had gained weight over that in the non-survivors and were insignificantly different in weight from that in the controls. The dilated heart seen in the non-survivors had disappeared and the dehydration of organs was no longer present. Survivors were therefore normal by 14 days post dose insofar as these measurements indicated.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the acute oral LD50 of potassium chloride was determined to be 3020 mg/kg bw.

Executive summary:

The acute toxicity potential of potassium chloride was investigated in a procedure equivalent to the OECD Guideline 401. Adult female rats of a Wistar strain were administered the test material by oral gavage at dose levels of 0, 2100, 2400, 2700, 3300, 3600 and 3900 mg/kg bw in distilled water and were observed for 14 days. Non-survivors died in 3.3 ± 3.2 hours from respiratory failure, sometimes following convulsions, and accompanied by gastroenteritis, dehydration of organs and early renal tubular necrosis. Survivors had anorexia, polydipsia, polyuria, fever, convulsive movements and gastrointestinal disturbances during the first 24 hours but rapidly returned to normal thereafter. Under the conditions of this study, the acute oral LD50 of the substance was determined to be 3020 mg/kg bw (Boyd, 1961).

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Study period:

17 August 2005 to 7 September 2005

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Justification for type of information:

Justification for read-across is attached in section 13 of the IUCLID dataset.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: CrI:CD(SD)IGS BR
- Age at study initiation: Approximately 8 weeks at the time of administration.
- Weight at study initiation: 174 to 194 g
- Fasting period before study: Yes. The feed was withdrawn the evening before the administration of the test material and was offered again about three hours post administration.
- Housing: Single caging (39 x 23 cm bottom area, 18 cm high) with wire mesh lids.
- Diet (e.g. ad libitum): feed gamma irradiated with 25 kGyCo, ad libitum.
- Water (e.g. ad libitum): Tap water from an automatic watering system, ad libitum.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Average of 22.0 °C
- Humidity (%): Average of 70.6 %
- Air changes (per hr): 12 per hour
- Photoperiod (hrs dark / hrs light): Artificial light from 6 a.m. to 6 p.m.

IN-LIFE DATES: From: 17 August 2005 To: 7 September 2005

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): The individual dose volumes were calculated using the bodyweights determined on the day of the administration.
- Justification for choice of vehicle: The test material was not soluble in water.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: As no prior information on the toxicity of the test material was available, a starting dose of 300 mg/kg bodyweight was chosen. The solutions were freshly prepared before dosing and were administered within 20 minutes.

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

3 female animals per step (6 animals in total per dose level)

Control animals:

no

Details on study design:

The test material was administered sequentially to groups of 3 animals per step, using a starting dose of 300 mg/kg. After the initial group of rats had been dosed, a second group of animals received the test material at a dose level of 300 mg/kg.
In the absence of any toxicological effects, the test material was administered to a third group of animals at a dose level of 2000 mg/kg. A fourth and final group of animals then received the test material at the 2000 mg/kg dose level.

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were performed within the periods 0 to 0.5, 0.5 to 1, 1 to 2, 2 to 4 and 4 to 6 hours after administration of the test material and then at least once a day for a total of 2 weeks. Observations included but were not limited to changes in skin, fur, eyes, the occurrence of secretions and excretions, autonomic activity, changes in gait, posture and the presence of convulsions.
Bodyweights were determined before administration, 7 days post administration and 14 days post administration. Body weight gain was calculated for each week of the study, i.e. between 0 and 7 days and between 7 and 14 days following dosing.
- Necropsy of survivors performed: yes. The animals were killed by inhalation of 80 % CO2 + 20 % air and subjected to a necropsy including a gross pathological examination.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity were observed.

Gross pathology:

No abnormalities were noted at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the acute oral LD50 of the substance was determined to be >2000 mg/kg bw

Executive summary:

The acute oral toxicity potential of the test substance in Sprague-Dawley rats was determined according to OECD Guideline 423 and EU Method B.1 under GLP conditions. The test substance was administered by oral gavage as a solution in corn oil; the dosing was performed sequentially to groups of 3 animals per step using a starting dose of 300 mg/kg bw and 2000 mg/bw as the second dose. The animals were observed for 14 days. There was no mortality and no clinical signs were observed. All animals showed expected gains in bodyweight throughout the observation period. Under the conditions of this study, the acute oral LD50 of the substance in rats 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

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

9 August 2005 to 25 August 2005

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

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
- Strain: CRL: CD (SD) BR SPF.
- Age at study initiation: Approximately 8 weeks (males) and 12 weeks (females) at the time of administration.
- Weight at study initiation: 270 to 284 g (males); 245 to 252 g (females).
- Fasting period before study: No.
- Housing: Single caging (39 cm x 23 cm x 18 cm cages) with wire mesh lids. Cages were sanitised once a week. Autoclaved aspen wood chips were used as bedding material; also changed weekly.
- Diet (e.g. ad libitum): gamma irradiated with 25 kGyCo, ad libitum.
- Water (e.g. ad libitum): Tap water, from an automatic watering system, ad libitum.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Average of 22 °C (continuous control and recording).
- Humidity (%): Average of 67 %(continuous control and recording).
- Air changes (per hr): 12 per hour.
- Photoperiod (hrs dark / hrs light): Artificial light from 6 am to 6 pm.

IN-LIFE DATES: From: 9 August 2005 To: 25 August 2005

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: A single dermal administration was performed by spreading the test material on an area of 6.5 x 8 cm (52 cm2). The test site was located on the dorsal thoracal region. The hair of the dorsal trunk was clipped with an electrical hair clipper (Aesculap GH, 0.1 mm cutter head) one day prior to application.
- % coverage: At least 10 % of the estimated body surface.
- Type of wrap if used: A cellulose patch (Pehazell, Hartmann AG) with the calculated amount of the test material on the surface was applied to the test site and held in place by fixing marginally with non irritating tape (Blenderm Wundpflaster, 3M). Patch and tape were covered semi-occlusively by a dressing (Fixomull Stretch, Fa. Beiersdorf).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test substance was wiped off using wet cellulose tissue, if necessary, once the dressing, the tape and the patch were removed at the end of the eposure period.
- Time after start of exposure: At the end of the exposure period (24 hours).

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bodyweight; the amounts were calculated and weighed for each individual using the body weights determined on the day of the administration.

Duration of exposure:

24 hours.

Doses:

2000 mg/kg bodyweight.

No. of animals per sex per dose:

5 animals per sex per dose.

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: Observations were performed at 0 to 0.5, > 0.5 to 1, > 1 to 2, > 2 to 4 and > 4 to 6 hours after administration and then at least once a day. Observations included but were not limited to changes in skin, fur, eyes, the occurrence of secretions and excretions, autonomic activity, changes in gait, posture and the presence of convulsions. No skin examination of the administration site was possible during the exposure period, while it was covered by the patch and wrappings.
Body weights were determined before administration, 7 and 14 days after dosing. Body weight gain was calculated for each week of the study, between 0 and 7 days and 7 and 14 days after dosing.
- Necropsy of survivors performed: Yes. All animals were killed by inhalation of 80 % CO2 + 20 % O2 14 days after dosing and subjected to a necropsy including a gross pathological examination.

- Justification for selection of the dose level: In a range finding study, three groups of one male and one female each were dosed with 400, 894 or 2000 mg/kg bodyweight. All animals survived for 7 days; therefore a limit-test with one dose of 2000 mg/kg body weight was performed. Both animals, dosed with 2000 mg/kg in the preliminary test were included into the main study.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There was no mortality. All animals survived until the scheduled termination of the study.

Clinical signs:

other: All animals were normal during the entire observation period. Exposed skin was not found to be altered by the test material.

Gross pathology:

All animals were normal at terminal necropsy.

Other findings:

No noteworthy sex difference in the response to the test material was derived from clinical observations or post-mortem findings.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the acute dermal LD50 of the substance in rats was determined to be >2000 mg/kg bw.

Executive summary:

The acute dermal toxicity potential of the test substance was determined according to OECD Guideline 402 and EU Method B.3 under GLP conditions. The test substance was administered once dermally on the dorsal thoracal region of 5 male and 5 female Sprague Dawley rats at a limit dose of 2000 mg/kg bw. A cellulose patch with the individually weighed amount of the test substance on the surface was applied to the test site and held in place by fixing marginally with non irritating tape. This was covered by a semi-occlusive dressing and left in place for 24 hours. There was no mortality and no local or systemic effects related to administration of the test material. All animals appeared normal at necropsy. Under the conditions of this study the acute dermal LD50 of the substance in rats was determined to be >2000 mg/kg bw (Bernat, 2005).

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 October 2000 to 2 November 2000

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: According to OECD 402 and GLP procedures.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Principles of method if other than guideline:

limit dose of 5000 mg/kg tested

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: Received from Ace Animals, Inc., Boyertown, PA on October 10, 2000
- Age at study initiation: Young adult (8-9 weeks)
- Weight at study initiation: males 218-246 grams and females 194-215 grams at experimental start
- Fasting period before study:
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals DHEW (NIH). Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet (e.g. ad libitum): Purina Rodent Chow #5012
- Water (e.g. ad libitum): Filtered tap water was supplied ad libitum by an automatic water dispensing system.
- Acclimation period: 9 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-21 °C
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

Type of coverage:

occlusive

Vehicle:

other: moistened with water

Details on dermal exposure:

TEST SITE
- Area of exposure: dose area of approximately 2 inches x 3 inches
- % coverage: approximately 10 % of the body surface

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): (conc. 85 %) Five thousand mg/kg of bodyweight of the test substance (6.25 g/kg of test mixture)
- Constant volume or concentration used: yes
- For solids, paste formed: yes

Duration of exposure:

24 hours

Doses:

(conc. 85 %) Five thousand mg/kg of bodyweight of the test substance (6.25 g/kg of test mixture)

No. of animals per sex per dose:

5 males and 5 females

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days (or other?) 14 days
- Frequency of observations and weighing:
- Necropsy of survivors performed: yes/no Yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
The animals were observed for mortality, signs of gross toxicity, and behavioral changes at 1 and 5 hours after application and at least once daily thereafter for 14 days. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea and coma.

Gross necropsies were performed on all animals. Tissues and organs of the thoracic and abdominal cavities were examined.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived

Clinical signs:

other: All animals appeared active and healthy

Gross pathology:

Gross pathology: All animals survived, gained weight and appeared active and healthy. There were no signs of gross toxicity, adverse pharmacologic effects or abnormal behavior. No gross abnormalities were noted for the animals necropsied at the conclusion of the 14-day observation period.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the acute dermal LD50 of the substance was determined to be >5000 mg/kg bw in rats.

Executive summary:

The acute dermal toxicity of the test substance was determined according to OECD Guideline 402 under GLP conditions. The test substance was administered once dermally to 5 male and 5 female Sprague Dawley rats at a limit dose of 5000 mg/kg bw. The test substance was moistened with water to form a paste and the animals were exposed for 24 hours. There was no mortality and no local or systemic effects related to administration of the test material. All animals appeared normal at necropsy. Under the conditions of this study the acute dermal LD50 of the substance in rats was determined to be >5000 mg/kg bw (Merkel, 2000).

Reference 3

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Study period:

9 August 2005 to 25 August 2005

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Justification for type of information:

Justification for read-across is attached in section 13 of the IUCLID dataset.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

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
- Strain: CRL: CD (SD) BR SPF.
- Age at study initiation: Approximately 8 weeks (males) and 12 weeks (females) at the time of administration.
- Weight at study initiation: 270 to 284 g (males); 245 to 252 g (females).
- Fasting period before study: No.
- Housing: Single caging (39 cm x 23 cm x 18 cm cages) with wire mesh lids. Cages were sanitised once a week. Autoclaved aspen wood chips were used as bedding material; also changed weekly.
- Diet (e.g. ad libitum): gamma irradiated with 25 kGyCo, ad libitum.
- Water (e.g. ad libitum): Tap water, from an automatic watering system, ad libitum.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Average of 22 °C (continuous control and recording).
- Humidity (%): Average of 67 %(continuous control and recording).
- Air changes (per hr): 12 per hour.
- Photoperiod (hrs dark / hrs light): Artificial light from 6 am to 6 pm.

IN-LIFE DATES: From: 9 August 2005 To: 25 August 2005

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: A single dermal administration was performed by spreading the test material on an area of 6.5 x 8 cm (52 cm2). The test site was located on the dorsal thoracal region. The hair of the dorsal trunk was clipped with an electrical hair clipper (Aesculap GH, 0.1 mm cutter head) one day prior to application.
- % coverage: At least 10 % of the estimated body surface.
- Type of wrap if used: A cellulose patch (Pehazell, Hartmann AG) with the calculated amount of the test material on the surface was applied to the test site and held in place by fixing marginally with non irritating tape (Blenderm Wundpflaster, 3M). Patch and tape were covered semi-occlusively by a dressing (Fixomull Stretch, Fa. Beiersdorf).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test substance was wiped off using wet cellulose tissue, if necessary, once the dressing, the tape and the patch were removed at the end of the eposure period.
- Time after start of exposure: At the end of the exposure period (24 hours).

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bodyweight; the amounts were calculated and weighed for each individual using the body weights determined on the day of the administration.

Duration of exposure:

24 hours.

Doses:

2000 mg/kg bodyweight.

No. of animals per sex per dose:

5 animals per sex per dose.

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: Observations were performed at 0 to 0.5, > 0.5 to 1, > 1 to 2, > 2 to 4 and > 4 to 6 hours after administration and then at least once a day. Observations included but were not limited to changes in skin, fur, eyes, the occurrence of secretions and excretions, autonomic activity, changes in gait, posture and the presence of convulsions. No skin examination of the administration site was possible during the exposure period, while it was covered by the patch and wrappings.
Body weights were determined before administration, 7 and 14 days after dosing. Body weight gain was calculated for each week of the study, between 0 and 7 days and 7 and 14 days after dosing.
- Necropsy of survivors performed: Yes. All animals were killed by inhalation of 80 % CO2 + 20 % O2 14 days after dosing and subjected to a necropsy including a gross pathological examination.

- Justification for selection of the dose level: In a range finding study, three groups of one male and one female each were dosed with 400, 894 or 2000 mg/kg bodyweight. All animals survived for 7 days; therefore a limit-test with one dose of 2000 mg/kg body weight was performed. Both animals, dosed with 2000 mg/kg in the preliminary test were included into the main study.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There was no mortality. All animals survived until the scheduled termination of the study.

Clinical signs:

other: All animals were normal during the entire observation period. Exposed skin was not found to be altered by the test material.

Gross pathology:

All animals were normal at terminal necropsy.

Other findings:

No noteworthy sex difference in the response to the test material was derived from clinical observations or post-mortem findings.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the acute dermal LD50 of the substance in rats was determined to be >2000 mg/kg bw.

Executive summary:

The acute dermal toxicity potential of the test substance was determined according to OECD Guideline 402 and EU Method B.3 under GLP conditions. The test substance was administered once dermally on the dorsal thoracal region of 5 male and 5 female Sprague Dawley rats at a limit dose of 2000 mg/kg bw. A cellulose patch with the individually weighed amount of the test substance on the surface was applied to the test site and held in place by fixing marginally with non irritating tape. This was covered by a semi-occlusive dressing and left in place for 24 hours. There was no mortality and no local or systemic effects related to administration of the test material. All animals appeared normal at necropsy. Under the conditions of this study the acute dermal LD50 of the substance in rats was determined to be >2000 mg/kg bw (Bernat, 2005).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute Toxicity: Oral

Crude Tall oil

The acute oral toxicity potential of the test substance in Sprague-Dawley rats was determined according to OECD Guideline 423 and EU Method B.1 under GLP conditions. The test substance was administered by oral gavage as a solution in corn oil; the dosing was performed sequentially to groups of 3 animals per step using a starting dose of 300 mg/kg bw and 2000 mg/bw as the second dose. The animals were observed for 14 days. There was no mortality and no clinical signs were observed. All animals showed expected gains in bodyweight throughout the observation period. Under the conditions of this study, the acute oral LD50 of the substance in rats was determined to be >2000 mg/kg bw (Wolf, 2005).

Potassium chloride

The acute oral toxicity potential of the test substance in Sprague-Dawley rats was determined according to OECD Guideline 423 and EU Method B.1 under GLP conditions. The test substance was administered by oral gavage as a solution in corn oil; the dosing was performed sequentially to groups of 3 animals per step using a starting dose of 300 mg/kg bw and 2000 mg/bw as the second dose. The animals were observed for 14 days. There was no mortality and no clinical signs were observed. All animals showed expected gains in bodyweight throughout the observation period. Under the conditions of this study, the acute oral LD50 of the substance in rats was determined to be >2000 mg/kg bw.

 

Acute Toxicity: Dermal

Crude Tall oil

The acute dermal toxicity potential of the test substance was determined according to OECD Guideline 402 and EU Method B.3 under GLP conditions. The test substance was administered once dermally on the dorsal thoracal region of 5 male and 5 female Sprague Dawley rats at a limit dose of 2000 mg/kg bw. A cellulose patch with the individually weighed amount of the test substance on the surface was applied to the test site and held in place by fixing marginally with non irritating tape. This was covered by a semi-occlusive dressing and left in place for 24 hours. There was no mortality and no local or systemic effects related to administration of the test material. All animals appeared normal at necropsy. Under the conditions of this study the acute dermal LD50 of the substance in rats was determined to be >2000 mg/kg bw (Bernat, 2005).

Potassium nitrate

The acute dermal toxicity of the test substance was determined according to OECD Guideline 402 under GLP conditions. The test substance was administered once dermally to 5 male and 5 female Sprague Dawley rats at a limit dose of 5000 mg/kg bw. The test substance was moistened with water to form a paste and the animals were exposed for 24 hours. There was no mortality and no local or systemic effects related to administration of the test material. All animals appeared normal at necropsy. Under the conditions of this study the acute dermal LD50 of the substance in rats was determined to be >5000 mg/kg bw (Merkel, 2000).

Justification for classification or non-classification

Based on the results of the acute oral and dermal toxicity studies with the read-across substance crude tall oil in rats, no classification is warranted for acute toxicity according to the EU CLP Regulation (EC) No. 1272/2008.