complex reaction mass of Chinese gum rosin post reacted with acrylic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

434-230-1

EC Name:

-

Cas Number:

144413-22-9

Molecular formula:

Not applicable - the substance is an UVCB

IUPAC Name:

1,4a-dimethyl-7-(propan-2-yl)-1,2,3,4,4a,4b,5,6,10,10a-decahydrophenanthrene-1-carboxylic acid; prop-2-enoic acid

Test material form:

other: pale yellow blocks

Details on test material:

- Chemical name: Rosin acid reaction products with acrylic acid hydrogenated

Test animals

Species:

rat

Strain:

other: Sprague-Dawley CD

Sex:

male/female

Details on test animals or test system and environmental conditions:

ANIMLAS
Male and female Sprague-Dawley CD strain rats supplied by CharIes River (UK) Ltd, Margate, Kent, UK were used. At the start of the main study the males weighed 202 to 241 g, and the females 202 to 220g, and were eight to twelve weeks old. After an acclimatisation period of at least five days the animals were selected at random and given a number unique within the cage by tail marking.

HUSBANDRY
The animals were housed in groups of up to three by sex in solid-floor polypropylene cages furnished with woodflakes. With the exception of an
overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food (Rat and Mouse Expanded Diet No.1, Special Diets Services Limited, Witham, Essex, UK) was allowed throughout the study.

ENVIRONMENTAL CONDITIONS
The animal room was maintained at a temperature of 19 to 23°C and relative humidity of 49 to 64%. The rate of air exchange was approximately fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was
calculated according to the fasted bodyweight at the time of dosing.

Doses:

200 and 2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

PREPARATION
For the purpose of the study the test material was freshly prepared, as required, as a suspension at the appropriate concentration in arachis oil BP. Arachis oil BP was used because the test material did not suspend in distilled water or other aqueous vehicles.
Determination by analysis of the concentration, homogeneity and stability of the test material preparations was not appropriate because it was not specified in the Study Plan and is not a requirement of the Test Guideline.

STUDY DESIGN
No toxicity data was available therefore a starting dose of 200 mg/kg in females was used.
Groups of fasted animals were therefore treated sequentially as follows:
- 3 Females | 200 mg/kg bw | conc. 20 mg/mL | volume 10 mL/kg
- 3 Males | 200 mg/kg bw | conc. 20 mg/mL | volume 10 mL/kg
- 3 Females | 2000 mg/kg bw | conc. 200 mg/mL | volume 10 mL/kg
- 3 Males | 2000 mg/kg bw | conc. 200 mg/mL | volume 10 mL/kg

All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each sex and each dose level to confirm the survival of the previously dosed animals.
The animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment or at death.
At the end of the observation period the surviving animals were killed by cervical dislocation. All animals were subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

DATA EVALUATION
The number of animals dying during the study, or killed for humane reasons, was determined. The nature, severity, time of onset and duration of toxic effects were also determined. Effects on bodyweights and abnormalities noted at necropsy were identified. Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test material was made.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

One female dosed at 2000 mg/kg was found dead one day after dosing.

Clinical signs:

other: Hunched posture, pilo-erection, decreased respiratory rate and laboured respiration were noted in the two surviving females dosed at 2000 mg/kg bodyweight. No signs of systemic toxicity were noted in all other treated animals throughout the study.

Gross pathology:

No abnormalities were noted at necropsy of animals killed at the end of the study period.
Haemorrhagic lungs, dark liver, dark kidneys and slight haemorrhage of the gastric mucosa were noted at necropsy of the female that died during the study.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 of the test material, Arakawa KE-604, in the Sprague-Dawley CD strain rat, was estimated to be greater than 2000 mg/kg bodyweight. No symbol and risk phrase are required according to EU labelling regulations.

Executive summary:

A study was performed to assess the acute oral toxicity of the test material following a single oral administration to the Sprague-Dawley CD strain rat. The method followed that in the OECD Guidelines for Testing of Chemicals No. 423 "Acute Oral Toxicity - Acute Toxic Class Method" (adopted 22 March 1996) and Method B1 tris of Commission Directive 96/54/EC (which constitutes Annex V of Council Directive 67/548/EEC).

The results may be used as a basis for classification and labelling under Annex VI of CounciI Directive 67/548/EEC (as adapted to technical progress by Commission Directive 93/21/EEC) relating to the classification, packaging and labelling of dangerous substances.

Using all available information, 200 mg/kg bodyweight was selected as the starting dose.

A group of three fasted females was treated with the starting dose. This was followed by a group of three fasted animals of the other sex at the same dose level. Based on the results from this dose level further groups of fasted animals were treated at dose levels of 2000 mg/kg bodyweight. Dosing was performed sequentially.

The test material was administered orally as a suspension in arachis oil BP. The animals were observed 0.5, 1, 2 and 4 hours after dosing and then once daily for up to fourteen days. Bodyweights were recorded on Day 0 (day of dosing) and on Days 7 and 14, or at death. At the end of the observation period all animals were killed by cervical dislocation and were subjected to gross necropsy.

One female dosed at 2000 mg/kg was found dead one day after dosing.

Hunched posture, pilo-erection, decreased respiratory rate and laboured respiration were noted in the two surviving females dosed at 2000 mg/kg bodyweight. No signs of systemic toxicity were noted in all other treated animals throughout the study.

All animals showed expected gains in bodyweight over the study period.

No abnormalities were noted at necropsy of animals killed at the end of the study period. Haemorrhagic lungs, dark liver, dark kidneys and slight haemorrhage of the gastric mucosa were noted at necropsy of the female that died during the study.

No mortalities were noted in animals treated with 200 mg/kg bodyweight.

One mortality (female) was noted in animals dosed with 2000 mg/kg bodyweight.

The acute oral LD50 of the test material in the Sprague-Dawley rat was estimated to be greater than 2000 mg/kg.

No symbol and risk phrase are required according to EU labelling regulations.