Registration Dossier

Administrative data

Description of key information

Several studies (GLP and non-GLP, according or similar to OECD guideline 401 and 403) were conducted to evaluate the acute oral and dermal toxicity of the test item. Single oral and dermal administration of the material did not cause mortality or clinical signs of toxicity. Acute oral and dermal LD50 values were therefore estimated to be >5000 and > 2000 mg/kg bw, respectively. Inhalation toxicity was also examined, however 1h inhalation of 2 mg/l air is insufficient for classification and assessment of acute toxicity.

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:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1981
Deviations:
no
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
- Source: Kleintierfarm Madoerin AG, Fuellinsdorf, Switzerland
- Age at study initiation: 10 - 12 weeks
- Weight at study initiation: males: 208 - 246 g; females: 209 - 220 g
- Fasting period before study: 12 - 18 hours
- Housing: groups of five per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
2% solution
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg bw

Doses:
5000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Four times during test day 1, and daily during days 2-15. Bodyweight: Test days 1 (pre-administration), 8 and 15.
- Necropsy of survivors performed: yes
Statistics:
The LOGIT-Model could not be applied to the observed rates of death. The LD50 was calculated without use of a statistical model.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no deaths occurred
Mortality:
none
Clinical signs:
Dyspnea was observed in any rat within 1 to 5 hours after treatment. All animals had recovered within 24 hours after treatment.
Body weight:
Normal body weight gain throughout the study.
Gross pathology:
No pathologic organ changes were observed.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
5 000 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
Study period:
1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazleton Research Products, Inc. Denver, Pennsylvania
- Age at study initiation: 11 weeks
- Weight at study initiation: 2014 - 2224g
- Housing: singly
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 6d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22
- Humidity (%): 64-82
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal skin
- % coverage: 18-20
- Type of wrap if used: gauze binders that were secured with Derrniforme" tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): sites wiped with wet disposable paper towels moistened with tepid tap wate
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- For solids, paste formed: no
Duration of exposure:
24h
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: rabbits were observed at approximately 1.0, 3.0 and 4.0 hours post-dose on day 0 and once daily thereafter for 14 days, body weights were obtained and recorded on study days 0 (initiation), 7 and 14 (study termination).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, dermal observations
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
There were no deaths during the study.
Clinical signs:
Five rabbits had abnormal defecation (soft stool, mucoid feces) on day 0 or 1. One of these animals also had wet, and subsequently, dry brown urogenital matting. These findings were considered to be a result of the bandaging / restraint procedures used and not related to the test material. An additional spontaneous occurrence of soft stool was noted on day 9 for one animal. There were no other clinical findings.
Body weight:
There were no remarkable changes or differences noted in body weights during the study.
Gross pathology:
Accessory splenic tissue, a common congenital abnormality in this strain of rabbit, was noted for four animals at the terminal necropsy. There were no other gross necropsy findings for all examined tissues.
Other findings:
The test material induced generally very slight to slight erythema on all rabbits and very slight to slight edema on eight rabbits. There was a single occurrence of moderate erythema at the day 1 observation. Desquarnation was present on five sites by day 7. There were no other dermal findings. One site had very slight erythema at study termination (day 14).
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

Acute oral toxicity

Three studies were performed to evaluate acute oral toxicity of the test item. In the key study, the test material dissolved in an aqueous solution 2% CMC was administered in a single dose by gavage to male and female Wistar rats (RCC, 1984). All animals were checked daily for mortality / viability and clinical signs of toxicity during days 1 -15; body weights were recorded on days 1, 8 and 15. None of the test animals died. Dyspnea was observed in any rat within 1 to 5 hours after treatment; all animals had recovered within 24 hours after treatment. Normal body weight gain was recorded throughout the study. Pathologic organ changes were not observed. The LD50 was therefore considered to be > 5000 mg/kg bw. Two other studies were conducted to examine acute oral toxicity: one assay was performed in hens (TSCATS, 1980) and the other one in rats (TSCATS, 1975). In the hen study, groups of 4 hens were dosed with the test item by gavage at dose levels of 800, 1200, 1800, 2700, 4050 and 6080 mg/kg bw. All hens survived until scheduled day of necropsy without any signs of toxicity; the hens remained normal in respect of appearance, mood and locomotor function throughout the observation period. No substance related findings were reported during necropsy and the LD50 was reported as 6080 mg/kg body weight. The third available study performed in rats was not taken into consideration, since it was performed at IBT, a CRO known for having falsified study reports. The reliability of this report can not be judged and therefore the study results are included in the dossier, but not taken into consideration.

Acute dermal toxicity

Two studies were conducted to examine acute dermal toxicity of the test item. In the key study (WIL, 1994), 2000 mg/kg bw of the material were applied onto skin of 5 male or female rabbits for 24h under semi-occlusive conditions. The animals were observed for mortality, clinical signs and skin irritation for 14d. There were no deaths, test material related clinical findings, remarkable body weight changes or test material related gross necropsy findings. The test material induced generally very slight to slight erythema on all rabbits and very slight to slight edema on eight rabbits. There was a single occurrence of moderate erythema. Desquamation was present on five sites by day 7. There were no other dermal findings. Dermal irritation decreased over the study period with one rabbit having very slight erythema at study termination (day 14). Based on the data obtained, the LD50 was found to be greater than 2000 mg/kg when applied once to the shaved, intact skin of male and female albino rabbits. The second study (Kemron, 1978), performed in 10 male rabbits, gave not hint for acute toxicity after a 24h application of 200 mg/kg bw onto skin.

Acute inhalation toxicity

The compound was analysed for its inhalative toxicity in a non-GLP study similar to OECD guideline 403 (TSCAT, 1978). Rats were exposed to 2 mg/l air for 1h (whole body) and thereafter observed for 14d. All animals survived until scheduled day of necropsy; clinical signs were not observed. However, 1h inhalation of 2 mg/l air is insufficient for classification and assessment of acute toxicity.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

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 toxicity under Regulation (EC) No. 1272/2008.