Formaldehyde, telomer with 1,3-benzenedimethanamine, 1,3-benzenediol and ethenylbenzene

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March-May 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000; including the most recent partial revisions

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Formaldehyde, telomer with 1,3-benzenedimethanamine, 1,3-benzenediol and ethenylbenzene

EC Number:

615-240-7

Cas Number:

710292-85-6

Molecular formula:

Not available for this UVCB

IUPAC Name:

Formaldehyde, telomer with 1,3-benzenedimethanamine, 1,3-benzenediol and ethenylbenzene

Details on test material:

- Name of test material (as cited in study report): HK-128
- Physical state: red-violet waxy solid

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: young adult animals (approx. 12 weeks old)
- Weight at study initiation: +/- 20% of the sex mean
- Housing: Individually housed in labeled Makrolon cages containing sterilized sawdust as bedding material and paper as cage enrichment
- Diet: free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany)
- Water: free access to water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.0-22.2
- Humidity (%): 31-65
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Deviations from the minimum level of relative humidity occurred. Laboratory historical data do not indicate an effect of the deviations.

IN-LIFE DATES: 15-29 March 2012

Administration / exposure

Type of coverage:

occlusive

Vehicle:

propylene glycol

Details on dermal exposure:

One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.
The test substance formulation was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The test substance formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.
Frequency: Single dosage, on Day 1.
Washing: Following application, dressings were removed and the skin cleaned of residual test substance using tap
water.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor.
- Dosage preparation: The formulation (w/w) was prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of the vehicle. No correction was made for purity of the test substance. In order to obtain homogeneity, the test substance (formulations) were heated in a water bath with a maximum temperature of 80ºC for a maximum of 31 minutes. The test substance formulation was allowed to cool down to a temperature of maximally 40ºC prior to dosing.

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: twice daily
Body weights: days 1 (pre-administration), 8 and 15
- Necropsy of survivors performed: yes

Statistics:

None

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:

No mortality occurred.

Clinical signs:

other: Hunched and/or flat posture, piloerection, chromodacryorrhoea, ptosis, quick breathing and/or hyperthermia were noted in the majority of animals between Days 1 and 10. General erythema, scales, scabs and/or red staining were seen in the treated skin-area

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 of HK 128 in Wistar rats was established to exceed 2000 mg/kg bw.
Based on these results: according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures, HK 128 does not have to be classified and has no obligatory labelling requirement for dermal toxicity.