Registration Dossier

Administrative data

Description of key information

The oral LD50 in rats is >3000 mg/kg bw (Hüls 1989). The dermal LD50 in rats is > 2000 mg/kg bw (TC 2012).

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:
2/3 to 17/3 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: similar to guideline study, non-GLP and no individual data reported
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
-Strain: Wilmslow Wistar
-Source: Harlan Winkelmann GmbH, 33167 Borchen
- Age at study initiation: young adults
- Weight at study initiation: average 153 g
- Fasting period before study: 16 hours before application
- Housing: 5 animals/macrolon III cage
- Diet: R10 allein diät Ssniff laboratory rat feed ad libitum
- Water: ad libitum
- Acclimation period: 5-8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±1
- Humidity (%): 60±5%
- Air changes (per hr):15/hr
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 02-03-1989 To: 17-03-1989
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE: NA

MAXIMUM DOSE VOLUME APPLIED: 3.75 cm3/kg bw

Doses:
3000 mg/kg bw
No. of animals per sex per dose:
5/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs: until 6 hours and daily thereafter
Body weight:on day 0, 1, 7, 14
- Necropsy of survivors performed: yes
- Other examinations performed: macrocopic investigations
Statistics:
NA limit test
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3 000 mg/kg bw
Based on:
test mat.
Mortality:
no mortality
Clinical signs:
ventro-lateral recumbency, piloerection and diarrhea in males during first 24 hours.
Thereafter no observations
Body weight:
within normal ranges
Gross pathology:
thinkening of the forestomach mucosa
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 in rats is > 3000 mg/kg bw
Executive summary:

In a limit test rats received 3000 mg/kg bw of the test substance. No mortality occurred. The LD50 is > 3000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 000 mg/kg bw
Quality of whole database:
The LD50 is > 3000 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
Study period:
03-10-2012 to 18-10-2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: study according to guideline under GLP
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes (incl. certificate)
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: Toxi-Coop Zrt. 1103 Budapest, Cserkesz u. 90.
- Age at study initiation: Not indicated
- Weight at study initiation: Males 268 - 280 g; females 225 - 231 g
- Fasting period before study: NA
- Housing: 1/cage in Type II polypropylene/polycarbonate cages
- Diet: ssniff® SM R/M-Z+H complete diet ad libitum
- Water: ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 8-12
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From 03-10-2012 To: 18-10-2012
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 10% of body surface
- Type of wrap if used: semi occlusive gauze

REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsed with water
- Time after start of exposure: 24 hours

TEST MATERIAL: 2000 mg/kg bw
Duration of exposure:
24 hours with a 14 day observation period
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5/sex/dose
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations:
mortality twice daily;
clinical signs at 1 and 5 hours after removal of the dressing, daily thereafter
body weight on day 1 (before treatment), 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
Statistics:
NA limit test
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None
Clinical signs:
local effects related to irritation (all reversible at day 7) :
redness 3/5 males
desquamation 1/5 males; 1/5 females
crustiness: 2/5 males
Body weight:
within normal ranges
Gross pathology:
hydrometra in 2/5 females
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 for dermal toxicity is >2000 mg/kg bw
Executive summary:

A single dose of the test substance at 2000 mg/kg bw was applied dermally to rats (5/sex). Signs of toxicity were limited to local irritant effects that were fully reversible after day 7. The LD50 for dermal toxicity is >2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The LD50 is > 2000 mg/kg bw

Additional information

No toxicity after acute oral and dermal exposure was observed.


Justification for selection of acute toxicity – oral endpoint
similar to guideline study, non-GLP and no individual data reported

Justification for selection of acute toxicity – dermal endpoint
study under GLP according to the guideline

Justification for classification or non-classification

The substance does not need to be classified for acute toxicity. Based on the viscosity data available (kinematic viscosity 1.107 mm²/s at 40°C) the substance needs to be classified as H304.