Registration Dossier

Administrative data

Description of key information

oral: LD50 > 2000 mg/kg bw; Evonik, 1571/0016, 2008, OECD 420
dermal: LD 50 > 2000 mg/kg, BASF, 11A0015/089114, 2009, OECD 402

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study.
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Safepharm Laboratories Limited, Shardlow, Derbyshire, UK
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Limited, Bicester, Oxon, UK
- Age at study initiation: eight to twelve weeks of age
- Weight at study initiation: mean: 174 g
- Fasting period before study: overnight
- Housing: in groups of up to four
- Diet: free access to Certified Rat and Mouse Diet (with the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing)
- Water: free access to drinking water (with the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing)
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.38 ml/kg

Doses:
2000 mg/kg
No. of animals per sex per dose:
5 female animals
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical observations were made 0.5, 1, 2, and 4 hours after dosing and subsequently once daily for up to fourteen days. Morbidity and mortality checks were made twice daily. Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: yes
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
There were no signs of systemic toxicity.
Body weight:
All animals showed expected gains in bodyweight.
Gross pathology:
No abnormalities were noted at necropsy.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw

Acute toxicity: via inhalation route

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Bioassay-Labor fuer biologische Analytik GmbH, Heidelberg, Germany
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: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: Young adult animals (male animals approx. 8 weeks, female animals approx. 12 weeks)
- Weight at study initiation: Animals of comparable weight (± 20% of the mean weight); mean(males): 233 g; mean(females): 214.4 g
- Housing: Single housing
- Diet: VRF1(P); SDS Special Diets Services, Altrip, Germany
- Water: Tap water ad libitum
- Acclimation period: Acclimatization period at least 5 days before the beginning of the experimental phase.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 26
- Humidity (%): 20 - 80
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: clipped skin (dorsal and dorso-lateral parts of the trunk); the application area comprised at least 10% of body surface area.
- Type of wrap if used: covering of the application site with a semiocclusive dressing (the bandage consists of four layers absorbent gauze, Ph. Eur. Lohmann GmbH & Co. KG and Fixomull stretch (adhesive fleece), Beiersdorf AG) for 24 hours;

REMOVAL OF TEST SUBSTANCE
- Washing: Rinsing of the application site with warm water.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.31 ml/kg

Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
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.
Scoring of skin findings: Individual readings 30 – 60 minutes after removal of the semiocclusive dressing (day 1), as a rule weekly thereafter and on the last day of observation. The evaluation of skin reactions was performed according to Draize, J.H. (1959): Appraisal of the safety of chemicals in foods, drugs and cosmetics.
Mortality: A check for any dead or moribund animal was made at least once each workday.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
No signs of systemic toxicity or skin effects were observed in the animals and no local effects were observed.
Body weight:
The mean body weight of the male animals increased within the normal range throughout the study period.
The mean body weight of the female animals slightly decreased during the first post-exposure observation week, but increased during the second week within the normal range.
Gross pathology:
No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw

Additional information

Oral:

In an acute oral toxicity study (OECD 420, Evonik, 1571/0016, 2008), groups of fasted 8 -12 week old rats (5 female Wistar rats) were given a single oral dose of the test substance at 2000 mg/kg bw. and observed for 14 days. No mortality occurred and normal body weight gain were found in this study. There were no signs of systemic toxicity and no deviations from normal morphology were found. Two further supporting studies showed similar results.

Dermal:

In an acute dermal toxicity study (OECD 402, BASF, 11A0015/089114, 2009), groups of 8 - 12 week old rats (5/sex) were dermally exposed to undiluted test substance for 24 hours to at least 10% of body surface area at 2000 mg/kg bw. Animals then were observed for 14 days. No mortality occurred and no signs of systemic toxicity or skin effects were observed in the animals. No local effects were seen. The mean body weight of the male animals increased within the normal range throughout the study period. The mean body weight of the female animals slightly decreased during the first post-exposure observation week, but increased during the second week within the normal range. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for acute oral or dermal toxicity under Regulation (EC) No. 1272/2008.