Isooctadecanoic acid, reaction products with tetraethylenepentamine

Endpoint summary

Description of key information

Acute toxicity studies in rat were conducted with the registered substance.  No treatment related adverse clinical signs or mortality were observed and the LD50 was determined to be greater than 5000 mg/kg following oral administration and greater than 2000 mg/kg following dermal exposure. A study using inhalation route is unjustified as the registered substance will not be inhaled. 

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:

1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: A GLP study performed to a standardised guideline with sufficient detail to assess the quality of the data.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

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 Breeding Laboratories, Inc., Wilmington, Massachusetts
- Age at study initiation: The males were 87 days of age and the females were 94 days of age at the time of dosing.
- Weight at study initiation: The males weighed 344-393 grams, and the females weighed 215-243 grams at the time of dosing.
- Fasting period before study: yes, overnight prior to dosing
- Housing: The animals were housed individually in wire-bottom cages in an air-conditioned room.
- Diet/water (e.g. ad libitum): The animals had free access to Purina Laboratory Rodent Chow #5001 and water except during the overnight period prior to dosing when only water was available.
- Acclimation period: the animals were allowed a conditioning period of 36 days prior to dosing in the laboratory.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):23.2-23.5 °C
- Humidity (%): 57.7-64.5%
- Photoperiod (hrs dark / hrs light): The photoperiod consisted of a 12-hour light/dark cycle: lights on at 0630 and off at 1830.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Single doses of 5.0 g/kg of the undiluted test material were administered intragastrically to 5 fasted animals of each sex. Five fasted undosed animals of each sex served as controls.

Doses:

Single doses of 5.0 g/kg bw.

No. of animals per sex per dose:

5/sex/dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: The animals were dosed approximately 5 hours after the onset of the light cycle. They were observed frequently for any physiological or behavioral abnormalities on the day of dosing and at least once each weekday morning and late afternoon for 13 days after treatment; on weekends they were observed once daily. On Day 14, the animals were observed once prior to sacrifice.
- Frequency of observations and weighing: The animals were weighed immediately prior to dosing and at 2, 7, and 14 days after treatment. The mean body weights of the treated animals were compared to those of the respective controls using Student's t-test
- Necropsy of survivors performed: yes, all survivors were killed following the 14-day observation period were examined for gross pathological changes. The following organs and tissues were examined: skin, spleen, pancreas, esophagus, stomach, small and large intestine, liver, adrenals, kidneys, gonads, uterus or seminal vesicles, urinary bladder, heart, thymus, salivary glands, lungs, trachea, thyroid, and fat. Abnormal tissues were preserved in 10% (v/v) neutral buffered formalin and submitted for histopathological examination.
- Other examinations performed: Tissues were submitted to Histopathology Reference Laboratory, Oakland, California, for tissue processing and preparation of routine five-micron H&E stained sections. The tissue sections were evaluated for microscopic abnormalities at Chevron Environmental Health Center, Inc.

Statistics:

No data

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: One treated male was observed to have reduced food consumption 24 hours following administration. No other signs of toxicity were observed.

Gross pathology:

No compound-related gross or microscopic lesions were observed. Bilated dilated renal pelves in a treated male and one female were the only gross pathologic changes observed. Upon histopathological examination, moderate hydronephrosis with mild tubular regeneration was observed in the male and trace hydronephrosis was observed in the female.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 was considered to be >5 g/kg (>5000 mg/kg) based on the results.

Executive summary:

In a study conducted broadly in line with OECD guideline 401 and in accordance with GLP, single doses of 5.0 g/kg of the undiluted test material were administered intragastrically to five fasted male and female rats. No mortality was observed. The only sign of toxicity was reduced food consumption in one treated male 24 hours following adminitration. No compound-related gross or microscopic lesions were observed.

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 data are considered sufficient for risk assessment purposes.

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: The study was conducted according to an internationally approved guideline and followed Good Laboratory Practices.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

not specified

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: L.I.T. Rabbitry, Whitehall, Montana
- Age at study initiation: The males/females were 15-17 weeks of age at the time of dosing.
- Weight at study initiation: The males weighed 2.95-3.48 kilograms, and the females weighed 2.99-3.40 kilograms at the time of dosing.
- Housing: The animals were housed individually in wire-bottom cages in an air-conditioned room.
- Diet (e.g. ad libitum): The animals were fed a daily ration of Purina Laboratory Rabbit Chow HF #5326.
- Water (e.g. ad libitum): Free access to water.
- Acclimation period: conditioning period of 51 days prior to dosing in the laboratory.

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 70°F
- Humidity (%): 61.0-95.6%
- Photoperiod (hrs dark / hrs light): The photoperiod was a 12-hour light/dark cycle: lights on at 0630 and off at 1830.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The fur on the trunks of five animals of each sex was clipped on the day prior to dosing. Two grams per kilogram of body weight of the test material were applied to the trunk of each animal. The material was held in contact with the animal's skin by a plastic sheet wrapped around the animal's trunk, and paper towels were wrapped over the plastic sheet to prevent tearing. Collars were placed on the animals to prevent oral ingestion of the test material. The mean weights (+S.D.) of test material administered were 6.52 (0.43) g for males and 6.62 (0.16) g for females. FIve clipped animals of each sex, treated with 5.0 ml/kg of physiological saline, were wrapped as described above and served as the controls. The animals were dosed and wrapped approximately 4 - 5 hours after the onset of the light cycle.
After a 24-hour exposure period, the wrappings were removed from the animals. The remaining test material had become hardened and was unable to be removed with mineral oil, ethanol or acetone. The test material had adhered flaked away from the animals between Days 7 and 14. Collars remained on treated animals from Day 0 to Day 6 to prevent oral ingestion of residual test material and on controls for the same length of time.

Duration of exposure:

24 hours.

Doses:

2 g/kg bw of test material.

No. of animals per sex per dose:

5 per sex per dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: The animals were observed frequently for any physiological or behavioral abnormalities on the day of dosing and at least once each weekday morning and late afternoon for 13 days after treatment; on weekends, they were observed once daily. On Day 14, the animals were observed once prior to sacrifice.

The skin at the application site was scored for irritation at 1, 7, and 14 days after treatment using the modified scoring system of Draize et al.

- Frequency of observations and weighing: The animals were weighed immediately prior to dosing and at 2, 7, and 14 days after treatment. The mean body weights of the treated animals were compared to those of the respective controls using Student's t-test.

- Necropsy of survivors performed: yes, all survivors killed following the 14-day observation period were examined for gross pathological changes. The following organs and tissues were examined: skin, spleen, pancreas, stomach, small and large intestine, liver, adrenals, kidneys, gonads, uterus or seminal vesicles, bladder, heart, thymus, salivary glands, lungs, trachea, thyroid, and fat. Sections of skin from each animal and any abnormal tissues were preserved in 10% (v/v) neutral buffered formalin and submitted for histopathological examination.

- Other examinations performed: Tissues were submitted to Histopathology Reference Laboratory, Oakland, California, for tissue processing and preparation of routine five-micron H&E stained sections. Tissue sections were evaluated for microscopic abnormalities at Chevron Environmental Health Center, Inc.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality.

Clinical signs:

other: Signs of toxicity observed during the study included reduced food consumption in 4 treated animals of each sex from Day 1 to Day 7. Reddened nictitating membranes with yellow ocular discharge was observed in 2 females in the treated group. All treated a

Gross pathology:

Dry and flaky skin was observed in the application site of in all treated animals and slight erythema with no edema was present in three treated animals of each sex. A treated female was also observed to have a pin-point eschar in the application site. Patches of slight erythema with no edema was observed in the application site of a male and a pin-point eschar was observed in the application site of a female in the control group. Four females and one male in the control group were observed to have reddened skin in the taped region where eschars had sloughed. Another male in the control group was observed to have an abcess in the taped region.

A thymus with red-brown areas was observed in one female in the control group.

Microscopic compound related lesions in the skin consisted of trace to mild subchronic inflammation and hyperkeratosis; mild acanthosis and mild epidermal cursting were also observed. Similar lesions in the control group were much more focal or multifocal rather than diffuse in distribution pattern and did not occur in every rabbit.

Mild thymic congestion was an incidental observation occuring in a female in the control group.

Interpretation of results:

GHS criteria not met

Conclusions:

The test article, when administered neat dermally to 5 male and 5 female New Zealand white rabbits had an acute dermal LD50 of greater than 2 g/kg.

Executive summary:

Five adult rabbits of each sex were treated with a single dermal application of 2.00 g/kg of test material. No mortality was observed. Signs of toxicity observed during the study were reduced food consumption in both treated sexes and reddened nictitating membranes and yellow ocular discharge in the treated females. The skin in the application site had become thickened and cracked with severe erythema and eschars between the cracks by day 7. Dry and flaky skin, pin-point eschars and slight erythema with no edema were observed at the application site of animals through sacrifice on day 14. Microscopic compound-related lesions in the skin consisted of trace to mild hyperkeratosis, epidermal crusting, dermal inflammation and acanthosis. There were no other treatment-related pathological changes.

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 data are considered sufficient for risk assessment purposes.

Additional information

Justification for selection of acute toxicity – oral endpoint
Two studies were available to assess the acute toxicity of the registered substance following oral administration. Both studies had an LD50>5000 mg/kg. While both studies were conducted according to similar protocol, The Easter et al, 1985 was selected as the key study due to the additional performance of GLP.

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

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation 1272/2008, the test material does not require classification for acute toxicity.