Tall oil, maleated

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Study Initiation: October 8, 2013; Treatment Start: October 15, 2013; Experimental Completion: November 18, 2013; Study Completion: November 20, 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

up-and-down procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Tall oil, maleated

EC Number:

268-859-6

EC Name:

Tall oil, maleated

Cas Number:

68152-93-2

Molecular formula:

UVCB

IUPAC Name:

3,7-dimethyl-14,16-dioxo-19-(propan-2-yl)-15-oxapentacyclo[10.5.2.0²,¹¹.0³,⁸.0¹³,¹⁷]nonadeca-13(17),18-diene-7-carboxylic acid; 8-(7-hexyl-1,3-dioxo-1,3,3a,4,7,7a-hexahydro-2-benzofuran-4-yl)octanoic acid

Test material form:

liquid

Details on test material:

Lot No.: HD0258QH13

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

Test Animal Rattus norvegicus
Strain: CD® [Crl:CD®(SD)BR] Sprague-Dawley
Source: Charles River Canada, Montreal, Quebec
Number and Sex: 5 female rats were used.
Body Weight: Range 200.2 - 216.7 g after fasting. The weight variation in animals at the start of the study did not exceed ±20 percent of the mean weight.
Acclimatization Period: 7 days
Age at Study Start: Approximately 7 to 8 weeks
Animal Identification: Body colour coding, cage labels
Animal Housing and Maintenance: Female rats were individually housed in separate quarters in solid bottom cages. Individual animals were identified by colour coding; the animal number and group number also appeared on the outside of each cage to preclude mix-up. The animal room environment was controlled (targeted ranges: temperature 19 °C to 25 °C, relative humidity 30 - 70%, minimum 10 air changes per hour) and monitored. The photo-cycle was 12 hours light and 12 hours dark. Upon arrival all animals were submitted to a general physical examination and all were found healthy and were admitted. Teklad Certified Rodent Diet and water were offered ad libitum throughout the acclimatization and study periods, except as specified under “Preparation of Animals”.
The cage cleaning schedule, air filtration and recirculation, health checks and facility maintenance were carried out in accordance with the applicable Nucro-Technics’ Standard Operating Procedures, and such activities were recorded in the animal room records. Animals were housed and maintained according to the AAALAC International Guide for the Care and Use of Laboratory Animals, CCAC Guidelines for Care and Use of Experimental Animals and Nucro-Technics’ Standard Operating Procedures.
Animal Selection: The test population of animals was randomly selected from newly arrived, previously unused rats.
Preparation of Animals: All animals used for the Limit Test were fasted over-night. Food but not water was withheld beginning at 4:00 p.m. on the day preceding dosing, and was returned to the cages approximately 1 hour after dosing.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Doses:

The first animal was dosed at 2000 mg/kg. Since this animal survived, four additional animals were sequentially dosed at 2-day intervals. A total of five animals were dosed.
The test animals were dosed at 2000 mg/kg (2.0 mL/kg by volume of test item).

No. of animals per sex per dose:

The individual doses of the test item were individually calculated for each animal based on the body weight of the animal. All doses were administered orally using a feeding cannula inserted into the stomach of the animals.

Control animals:

no

Details on study design:

Method
The method used for conducting this study is the accepted standard described in the Organisation for Economic Co-operation and Development (OECD) Guideline for the Testing of Chemicals, Acute Oral Toxicity (Up-and-Down Procedure), Section 425, (OECD, 2008). The study was conducted in accordance with Nucro-Technics Study Plan No. CAN/275630, Appendix I.
Justification for Selection of Test System: The test system is internationally accepted for use in acute oral toxicity studies.
Test System:
Test Animal Rattus norvegicus
Strain CD® [Crl:CD®(SD)BR] Sprague-Dawley
Source Charles River Canada, Montreal, Quebec
Number and Sex 5 female rats were used.
Body Weight Range 200.2 - 216.7 g after fasting. The weight
variation in animals at the start of the study
did not exceed ± 20 percent of the mean
weight.
Acclimatization Period 7 days
Age at Study Start Approximately 7 to 8 weeks
Animal Identification Body colour coding, cage labels
Animal Housing and Maintenance
Female rats were individually housed in separate quarters in solid bottom cages. Individual animals were identified by colour coding; the animal number and group number also appeared on the outside of each cage to preclude mix-up. The animal room environment was controlled (targeted ranges: temperature 19 °C to 25 °C, relative humidity 30 - 70%, minimum 10 air changes per hour) and monitored. The photo-cycle was 12 hours light and 12 hours dark. Upon arrival all animals were submitted to a general physical examination and all were found healthy and were admitted. Teklad Certified Rodent Diet and water were offered ad libitum throughout the acclimatization and study periods, except as specified under “Preparation of Animals”. The cage cleaning schedule, air filtration and recirculation, health checks and facility maintenance were carried out in accordance with the applicable Nucro-Technics’ Standard Operating Procedures, and such activities were recorded in the animal room records. Animals were housed and maintained according to the AAALAC International Guide for the Care and Use of Laboratory Animals, CCAC Guidelines for Care and Use of Experimental Animals and Nucro-Technics’ Standard Operating Procedures.
Animal Selection
The test population of animals was randomly selected from newly arrived, previously unused rats.
Preparation of Animals
All animals used for the Limit Test were fasted over-night. Food but not water was withheld beginning at 4:00 p.m. on the day preceding dosing, and was returned to the cages approximately 1 hour after dosing.
Experimental Procedures
Limit Test
The first animal was dosed at 2000 mg/kg. Since this animal survived, four additional animals were sequentially dosed at 2-day intervals. A total of five animals were dosed.
Dose Administration
The test animals were dosed at 2000 mg/kg (2.0 mL/kg by volume of test item). The individual doses of the test item were individually calculated for each animal based on the body weight of the animal. All doses were administered orally using a feeding cannula inserted into the stomach of the animals.
Observations During In-Life Phase
The animals were individually observed once during the first 30 minutes after dosing and periodically during the first 24 hours following dosing (with special attention given during the first 4 hours). Observations once daily were carried out for the remainder of the study. The animals were observed for 14 days after the dosing. Cageside observations were directed towards any changes in the skin and fur; eyes and mucous membranes; respiratory, circulatory, autonomic and central nervous system; and also somatomotor activity and behaviour pattern. Particular attention was directed to any observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and/ or coma. All observations were recorded daily for the entire study period using the In-Life Module V.6.1, and the entries were monitored by the Study Director. The body weights of the animals were determined prior to test item administration (i.e., Day 0), on Day 7 and on Day 14. Body weight gains were calculated. For calculation of LD50, results were entered into the Acute Oral Toxicity statistical program, V.1.0.
Post Mortem Examination
Gross necropsy was performed on each rat at the end of a 14-day observation period and necropsy included an examination of: external surfaces of the body; all orifices; cranial cavity; external surfaces of the brain and spinal cord; nasal cavity and paranasal sinuses; thoracic, abdominal, and pelvic cavities and viscera.
Archive
The original copy of the protocol, and all raw data that were generated at Nucro-Technics and a copy of the final report will be stored in the Nucro-Technics’ archives for 6 years. Nucro-Technics will notify the Sponsor in advance of the end of this period to allow the Sponsor to secure alternative storage facilities, if required.

Statistics:

For calculation of LD50, results were entered into the Acute Oral Toxicity statistical program, V.1.0.

Results and discussion

Preliminary study:

The first animal was dosed at 2000 mg/kg. Since this animal survived, four additional animals were sequentially dosed at 2-day intervals. A total of five animals were dosed.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortalities were observed post dosing and during the 14-day observation period in any of the animals.

Clinical signs:

other: All clinical signs appear normal

Gross pathology:

No organs with gross findings were observed in necroscopy observations

Other findings:

none

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the foregoing results, the acute oral LD50 in rats of the test item, Tall Oil, Maleated (EnvaMul™ 600) was found to be greater than 2000 mg/kg. Therefore, the test item is considered not to present a significant acute toxic risk if swallowed.

Executive summary:

An Acute Oral Toxicity Study of the test item, Tall Oil, Maleated (EnvaMul™ 600), was carried out at Nucro-Technics according to Study Plan No. CAN/275630. The first animal was dosed at 2000 mg/kg, 2.0 mL/kg by dose volume. Since this first animal survived, four additional test animals were dosed at 2-day intervals. A total of 5 female CD (Sprague-Dawley) rats were dosed. All animals received the test item by oral gavage using a feeding cannula inserted into the stomach of the animals. The animals were observed for a 14-day period after dosing. Body weights were recorded prior to test item administration (i.e., Day 0), on Day 7 and prior to necropsy on Day 14. No mortalities were observed post dosing and during the 14-day observation period in any of the animals. All rats gained body weight by Day 7 and again by Day 14. At the end of a 14-day observation period, each animal was sacrificed and submitted for gross necropsy. No gross pathological findings were observed in any of the rats at necropsy. Based on the foregoing results, the acute oral LD50 in rats of the test item, Tall Oil, Maleated (EnvaMul™ 600), was found to be greater than 2000 mg/kg. Therefore, the test item is considered not to present a significant acute toxic risk if swallowed.