Rosin, fumarated, reaction products with formaldehyde

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted according to OECD Guideline 402 and EU Method B.3 with no deviations that affected the results of the study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Principles of method if other than guideline:

The test substance was applied to the clipped skin of male and female rats for 24 hr under a porous gauze dressing, and the animals observed for 14 days.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Rosin

EC Number:

232-475-7

EC Name:

Rosin

Cas Number:

8050-09-7

IUPAC Name:

8050-09-7

Constituent 2

Reference substance name:

Rosin

IUPAC Name:

Rosin

Details on test material:

-Identity (according to study report): Rosin
-Date received at Testing Laboratory: October 15, 2009
-Appearance: yellowish solid
-Storage: -20 °C
-Production date: June 2009
-Expiration date: June 2010
-Purity: 100%
-Code No.: PH-09/0286
-The test sample was used as supplied.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS:
-Source: Elevage JANVIER (53940 Le Genest St Isle –France)
-Animals: 10 (5 males and 5 females)
-Acclimation period: at least 5 days
-Weight at study initiation: Males = 216-229 grams; Females = 199-206 grams
-Age at study initiation: Males = 7 weeks; Females = 8 weeks
-Housing: 1/cage during treatment and 2-3/cage from Day 3 to termination of the observation period. The rats were kept in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid. Each cage contained sawdust bedding which was changed at least 2 times a week.
-Diet: Extralabo pellets from Pietrement (Diet M20 with Code 841201), available ad libitum
-Water: drinking water (tap-water from public distribution system) available ad libitum

ENVIRONMENTAL CONDITIONS:
-Room temperature (ºC): 20-26
-Relative humidity (%): 40-55
-Air exchanges: 15/hour
-Light: 12 hour light/dark cycle

IN-LIFE DATES:
-Date of experiment initiation: 3 Nov 2009
-Date of experiment termination: 17 Nov 2009

Administration / exposure

Type of coverage:

other: porous gauze dressing

Vehicle:

DMSO

Details on dermal exposure:

Approximately 24 hours prior to treatment, the fur was removed from the dorsal area of the trunk (at least 10% of the body surface area) of the animals by clipping. Just prior to dosing, 4 grams of the test substance was weighed, after being reduced to fine powder using a pestle and a mortar, and dimethylsulfoxide was added in a 20 mL volumetric flask. The preparation was magnetically agitated to obtain a yellow solution, just before being administered. Animals received by topical application, under porous gauze dressing, an effective dose of 2000 mg/kg bw of the test substance. The test substance was administered at a volume of 10 mL/kg bw for a 24-hour exposure period. After the exposure period, the gauze dressings were removed and the treated area was rinsed with dimethylsulfoxide.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5/sex/dose level

Control animals:

other: A current control study (TAD-2009-002) used distilled water to assess the strain of rat used and to give additional historical data. The method used met the requirements of OECD Guideline 402 and EU Meth. B.3. Study performed 23 June 2009 to 07 July 2009.

Details on study design:

Clinical Observations:
Animals were evaluated daily for the following: mortality, spontaneous activity, Preyer’s reflex, respiratory rate, convulsions, tremors, body temperature, muscle tone, palpebral opening, pupil appearance, salivation, lachrymation, righting reflex, and back hair appearance.

Body Weights:
Body weights were measured on Day 0 (just prior to dose administration), Day 2, Day 7 and Day 14.

Necropsy:
All animals were euthanized and a macroscopic examination performed at the completion of the 14-day observation period. Only organs with abnormalities were preserved for microscopic examination.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study.

Clinical signs:

other: No systemic clinical signs related to the administration of the test substance were observed. A slight dryness to dryness was noted on the treated area of one female (1/5) at 48 hours post-dose and of all animals (10/10) at 72 hours post-dose. On Days 6 a

Gross pathology:

Macroscopic examination of the animals at the end of the study did not reveal treatment-related changes.

Any other information on results incl. tables

The LD50 of the test substance is greater than 2000 mg/kg bw by the dermal route in male and female rats.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In an acute dermal toxicity test, no deaths were reported when a limit dose of 2000 mg/kg bw of Gum Rosin was applied to the clipped skin of male and female Sprague-Dawley rats for twenty-four hours under a porous gauze dressing. No test material-related clinical signs were observed during the study and skin irritation was limited to slight dryness at the test site. After an initial absence of body weight gain, all animals recovered and gained weight normally during the rest of the study. No gross abnormalities were observed at necropsy. Gum Rosin was not acutely toxic by the dermal route in male and female rats at a dose of 2000 mg/kg bw and, based on a dermal LD50 > 2000 mg/kg bw, it is not classified for acute lethality by the dermal route according to Directive 67/548/EEC, the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) or the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. Based on an absence of significant systemic signs, Gum Rosin is also not classified according to Directive 67/548/EEC, the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) or the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 for Specific Target Organ Toxicity – Single Exposure for the dermal route of exposure.

Executive summary:

In an acute dermal toxicity study, a group of five male and five female rats was administered a single dose of Gum Rosin topically, under porous gauze dressing, at a dose level of 2000 mg/kg bw in a dimethylsulfoxide vehicle for an exposure period of 24 hours. Under the conditions of this study, the dermal LD50 of Gum Rosin in male and female Sprague-Dawley rats was > 2000 mg/kg bw. No mortality was observed in the study and, after an absence of body weight gain was noted in all males and females on Day 2, the animals recovered and gained weight normally over the rest of the study period. No systemic clinical signs related to the administration of the test substance were observed. Other than a slight dryness to dryness noted at the treatment site of one or more animals at various times during the study, there were no signs of irritation, necrosis, ulceration or evidence of tissue destruction reported. At necropsy, no gross lesions were observed. Based on the results of this study, Gum Rosin is not acutely toxic to rats via the dermal route and therefore is expected to present a low toxicity hazard upon skin contact under conditions of normal use.