Registration Dossier

Administrative data

Description of key information

The acute dermal and oral toxicity of EUF was above 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 05 to November 27 (experimental period)
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH, 97633 Sulzfeld
- Age at study initiation: not detailed
- Weight at study initiation: 142-172g (on day of dosing)
- Fasting period before study: overnight
- Housing: In macrolon cages, 2 or 3 animals per cage
- Diet : ad libitum
- Water : e.g. ad libitum
- Acclimation period: 5 days

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

IN-LIFE DATES (DOSING): Sighting study: November 6th, 2007; Main study: November 14, 2007
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20%
- Amount of vehicle (if gavage): 80%
- Justification for choice of vehicle: Soluble in water


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Fixed dose method, started with 2000 mg/kg bw.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
1 female used for sighting study
4 females used for mauin experiment
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Body weight recording: day 0 (test start), day 7 day 14 ; Clinical signs: each rat was observed 30 min., 2, 4 and 6 hours post-dosing and daily thereafter over a period of 14 day

- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
No preterminal deaths. Therefore no statistical proceduresecessary
Preliminary study:
1 female was dosed at 2000 mg/kg bw.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no preterminal deaths. Therefore no CL determined
Mortality:
No animal died
Clinical signs:
Hunched posture and piloerection were observed from 30 min. p.a. onwards up to 6 hours. From Day 1 to the end of the observation period, the animals were free of any abnormalities.
Body weight:
Not affected
Gross pathology:
No specific findings

 

Table for Acute Oral Toxicity of TPI 1618

Dose [mg/kg bw]

Number of dead /
number of investigated

Time of death (range)

Observations

2000

females 0/4

n.a.

Clinical signs:
piloerection, hunched posture,

 

LD50value (females)

> 2000 mg/kg bw

 

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
The results of the study indicate that the acute oral toxicity in female animals was above 2000 mg/kg body weight.
Executive summary:

Study was performed according to OECD guideline 420 (fixed dose procedure). One dose level of 2000 mg/kg bw. was used and applied orally as single administration to 4 females rats.
All survivors were subjected to a 14 days post-treatment observation period. All rats were observed for clinical signs, body weight development. Macroscopic findings were recorded in all animals.

No animal died. Clinical signs observed at the 2000 mg/kg dose level were piloerection and hunched posture p to 6 hours post dosing. Body weight development was within normal ranges. No macroscopic organ findings were observed at necropsy.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
June 28, 2004 to July 21, 2004 (experimental phase)
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: DIMED Schönwalde
- Weight at study initiation: 210 – 261 g
- Fasting period before study: Overnight prior to dosing
- Housing: Macrolon Type III cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +-3
- Humidity (%): 55 +- 15
- Air changes (per hr): 10
- Photoperiod 12 hrs dark /12 hrs light

IN-LIFE DATES: From June 22, 204 to July 21, 2004
Type of coverage:
occlusive
Details on dermal exposure:
TEST SITE
- Area of exposure: 6x8 cm
- Type of wrap if used: 4-layer gauze packs fixed with Micropore tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 hours post dosing

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): used undilutedly

Duration of exposure:
24 hours
Doses:
2000 mg/kg bw (Limit test)
No. of animals per sex per dose:
5 males/5 females
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations 1, 3 and 6 hours after the start of dosing and daily thereafter over 14 days; body weights recorded on days 0, 7 and 14
- Necropsy of survivors performed: yes
Statistics:
No preterminal deaths; therefore no statistical procedures empoyed
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: CL not applicable
Mortality:
No mortalities
Clinical signs:
Males and females showed piloerection 1, 3 and 6 hours p.a. as well as on day 1. The skin and adjacent areas were yellowish discoloured caused by the test item.
Body weight:
No effects on body weights were noticed.
Gross pathology:
External examination of animals at termination of the study did not reveal any lesions of pathological significance.

Table for acute dermal toxicity: clinical signs and pathology

Dose (mg/kg bw.)

Number of dead /
number of investigated

Time of death (range)

Observations

2000 mg/kg

males 0/5,
females 0/5

n.a.

Clinical signs: Piloerection up to and including Day 1 p.a. in all animals

Pathology
no specific findings

LD50value

>2000 mg/kg bw.

 

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
The acute dermal toxicity is low with an LD50 greater than 2000 mg/kg bw.
Executive summary:

The study was performed according to OECD guideline 402 and designed as a limit-test using a single dose of 2000 mg/kg bw in rats. No pre-terminal deaths were observed in any of the rats after dermal application of 2000 mg/kg bw. Clinical signs were limited to piloerection up to and including Day 1 of dosing. Yellowish staining of the skin was induced by the test item.
The LD50for male and female rats after dermal exposure was greater than 2000 mg/kg bw. Thus no classification is required.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw

Additional information

Acute oral and dermal toxicity was investigated in studies according to current guidelines. The acute oral toxicity of EUF was above 2000 mg/kg bw in a limit test. Clinical signs observed in rats after oral application were hunched posture and piloerection. Pathology revealed no treatment-related effects.

An acute inhalation toxicity study with EUF has not been performed.

Though the existing and most recently performed acute dermal irritation study with EUF did not indicate EUF to be an irritant compound, however, irritation can nevertheless be expected if the test item is allowed to hydrolyse. The maximum releasable formaldehyde portion of 49% from EUF is expected to cause burns. Therefore, testing inhalation route is not regarded as scientifcally justified.

Justification for classification or non-classification

Acute oral toxicity

Based on the most recent data with LD50 values of > 2000 mg/kg bw, there is no need for a classification according to the CLP regulations of EC Directive 1272/2008 and GHS.

Acute inhalation toxicity

Classification not possible. No study performed.

Acute dermal toxicity

Based on the data with an acute dermal toxicity of >2000 mg/kg bw, there is no need for a classification according to the CLP regulations of EC Directive 1272/2008 and GHS.