Reaction mass of bis[4-(vinyloxy)butyl] hexane-1,6-diylbiscarbamate and 9,18-dioxo-3,8,19-trioxa-10,17-diazapentacos-1-en-25-yl [6-({[4-(vinyloxy)butoxy]carbonyl}amino)hexyl]carbamate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 December 2016 - 03 January 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

The study was performed as a data requirement for a registration in China.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

May 2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

August 1998

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF Guidelines

Version / remarks:

November 2000, including the most recent revisions

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

d.d. 3 November 2015

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

420-990-1

EC Name:

-

Cas Number:

146421-65-0

Molecular formula:

C20H36N2O6

IUPAC Name:

4-(ethenyloxy)butyl N-[6-({[4-(ethenyloxy)butoxy]carbonyl}amino)hexyl]carbamate

Constituent 2

Reference substance name:

4-(ethenyloxy)butyl N-{6-[({[6-({[6-({[4-(ethenyloxy)butoxy]carbonyl}amino)hexyl]carbamoyl}oxy)hexyl]oxy}carbonyl)amino]hexyl}carbamate

Cas Number:

1516571-16-6

Molecular formula:

C34H62N4O10

IUPAC Name:

4-(ethenyloxy)butyl N-{6-[({[6-({[6-({[4-(ethenyloxy)butoxy]carbonyl}amino)hexyl]carbamoyl}oxy)hexyl]oxy}carbonyl)amino]hexyl}carbamate

Test material form:

solid: flakes

Details on test material:

Appearance: White Flakes
Test item storage: At room temperature

Specific details on test material used for the study:

Adjustment was made for specific gravity (1.036) of the vehicle.

In order to obtain homogeneity, the test item (formulations) were heated in a water bath with a maximum temperature of 76.1ºC for a maximum of 38 minutes. The test item (formulations) were allowed to cool to a temperature of maximally 40ºC prior to dosing.

The test item preparations were stirred on a magnetic stirrer during application.

Test animals

Species:

rat

Strain:

other: Crl: WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females nulliparous and non-pregnant:yes
- Age at study initiation: approx. 10 weeks old
- Weight at study initiation: Males: 258 - 295 g, Females: 191 - 216 g.
- Housing: During the acclimatization period the animals were group housed in Makrolon cages (MIV type, height 18 cm) containing sterilized sawdust as bedding material and paper as cage-enrichment. During the study the animals were individually housed in Makrolon cages (MIII type, height 18 cm.).
- Diet: Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS (set to maintain)
- Temperature (°C): 18 - 24
- Humidity (%): 40 - 70
- Air changes (per hr): >= 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

occlusive

Vehicle:

propylene glycol

Remarks:

Specific gravity: 1.036

Details on dermal exposure:

TEST SITE
- Area of exposure: 18 cm^2 for females, 25 cm^2 for males
- % coverage: approx. 10% of the total body surface
- Type of wrap if used: 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.

REMOVAL OF TEST SUBSTANCE
- Washing: tap water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: 5000 mg/kg bodyweight
- Constant volume or concentration used: yes, 20 mL/kg bodyweight

Duration of exposure:

24 hours

Doses:

5000 mg/kg bodyweight

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations:
- Mortality: twice daily
- Clinical observations: at periodic intervals on the day of dosing and once daily thereafter.
- Body weights: on day 1 (pre-administration), day 8 and day 15.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

No mortality occurred.

Clinical signs:

other: Red nose was noted for three males and four females on day 2 only.

Gross pathology:

No abnormalities were seen at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of an acute dermal study (limit study), performed according to OECD/EC guidelines and GLP principles, The dermal LD50 value of URALAC P 1920C in Wistar rats was determined to exceed 5000 mg/kg body weight. As a consequence, URALAC P 1920C is not classified according to GHS and CLP criteria.

Executive summary:

An acute dermal study (limit study) was performed according to OECD/EC guidelines and GLP principles. Five male and five female rats were exposed to 5000 mg/kg bw and observed for 14 days. No mortality occurred. A red nose was noted for three males and four females on day 2 only. No unexpected changes in body weight gain occurred, no abnormalities were seen at necropsy. These reuslts demonstrate that the dermal LD50 value of URALAC P 1920C in Wistar rats exceeds 5000 mg/kg body weight. As a consequence, URALAC P 1920C is not classified according to GHS and CLP criteria.