Resin acids and Rosin acids, reaction products with formaldehyde, calcium salts

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 08 October 2012 to 08 November 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

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:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: Japan MAFF 8147

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:

Resin acids and Rosin acids, reaction products with formaldehyde, calcium salts

EC Number:

696-130-6

Cas Number:

1364681-45-7

Molecular formula:

Unspecified

IUPAC Name:

Resin acids and Rosin acids, reaction products with formaldehyde, calcium salts

Details on test material:

- Name of test material (as cited in study report): Resin acids and rosin acids, reaction products with formaldehyde, calcium salts
- Physical state: Solid / offwhite
- Analytical purity: 96.0 % w/w determined by Mass spectroscop
- Lot/batch No.: DMG 7245
- Expiration date of the lot/batch: July 05, 2016
- Stability under test conditions: The stability of the test item under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility.
- Storage condition of test material: Room temperature
- Homogeneity: The homogeneity of the test item preparation will be determined indirectly by concentration control analysis.

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Animal strain: Wistar / Cri:WI (Han)
- Source: Charles RiverWiga GmbH, Sulzfeld, Germany
- Age at study initiation: Young adult animals (female animals approx. 10 weeks)
- Mean weight at study initiation: Group 1: 186.7 ± 4.04; Group 2: 179.3 ± 0.58 g
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: Single housing; Makrolon cage, type Ill
- Diet: VRF1 (P); SDS Special Diets Services, Altrip, Germany)
- Water: Tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30- 70
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From 08 October 08 2012 to 30 October 2012

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Remarks:

Ph.Eur.

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20 g/100 mL
- Justification for choice of vehicle: Good homogeneity in olive oil Ph.Eur.
- Form of administration: Suspension

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: The test item preparation was produced for each application group shortly before application by stirring with a high speed homogenizer (Ultra-Turrax) and a magnetic stirrer. Additionally the homogeneity of the test item preparation during application was ensured by stirring with a magnetic stirrer.

Stability of the test item preparation: The stability of the test item in the vehicle was verified indirectly by concentration control or homogeneity analysis. The samples taken were stored at room temperature over the maximum duration of the administration period and were subsequently deep-frozen. Afterwards these samples were sent to the sponsor.

CLASS METHOD
- Rationale for the selection of the starting dose: By request of the sponsor a starting dose of 2000 mg/kg bw was chosen in the first step
with 3 female animals.
Because no mortality occurred, 2000 mg/kg bw were applied to another group of 3 female animals in the second step.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
• Body weight determination: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
• Clinical observations: Recording of clinical signs several times on the day of administration, and at least once daily thereafter each
workday for the individual animals.
• Mortality: A check for any dead or moribund animals was made at least once each workday.
• Pathology: Necropsy with gross-pathology examination on the last day of the observation period after sacrifice by CO2-inhalation in a chamber with increasing concentrations over time.
• Histology: No histological examinations were performed.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality was observed.

Mortality:

No mortality occurred.

Clinical signs:

2000 mg/kg bw (first test group):
- Impaired general state, dyspnoea and piloerection in all animals from hour 0 or hour 1 up to hour 3 and on day 1 after administration.
2000 mg/kg bw (second test group):
- Impaired general state and piloerection were observed in one out of three animals from hour 1 up to hour 5 and on day 1 after administration, whereas dyspnoea was noted from hour 1 up to hour 5 after administration in this animal.
- The other two animals showed piloerection and impaired general state on day 1 after administration only.

Body weight:

The mean body weight of all animals increased within the normal range throughout the study period.
Mean body weight at study day (g) first test group/ second test group:
day 0: 186.7 ± 4.04 / day 0: 179.3 ± 0.58
day 7: 220.3 ± 6.66 / day 0: 197.3 ± 3.00
day 14: 229.3 ± 6.11 / day 0: 208.3 ± 1.53

Gross pathology:

There were no macroscopic pathological findings in the animals sacrificed at the end of the observation period.

Other findings:

No other findings.

Any other information on results incl. tables

Table 1 Acute oral toxicity.

 

Dose [mg/kg bw]	Mortality		Clinical signs
	N*	%	after administration
Females
1^stadministration
2000	0/3	0	Hour 0 – day 1
2^ndadministration
2000	0/3	0	Hour 1 – day 1

*N= number of dead animals / number of animals used